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Sample records for human placenta cord

  1. Dielectric properties of human placenta, umbilical cord and amniotic fluid

    Energy Technology Data Exchange (ETDEWEB)

    Peyman, A [Physical Dosimetry Department, Health Protection Agency, Chilton, Didcot OX11 0RQ (United Kingdom); Gabriel, C [MCL-P, Newbury RG14 5PY, Berkshire (United Kingdom); Benedickter, H R; Froehlich, J, E-mail: Azadeh.peyman@hpa.org.uk [Electromagnetic Fields and Microwave Electronics Laboratory, Swiss Federal Institute of Technology, Zurich (Switzerland)

    2011-04-07

    The dielectric properties of freshly delivered human placenta, umbilical cord and amniotic fluid have been acquired at 37 deg. C and in the frequency range of 200 MHz-10 GHz. The experimental data were fitted to a Cole-Cole expression. The results show that dielectric properties of the umbilical cord are significantly higher than placenta due to the presence of high water content Wharton's jelly. The results also demonstrate large differences in the dielectric properties of amniotic and cerebrospinal fluids. The data presented can be used in numerical simulations of the exposure of pregnant women to electromagnetic fields. (note)

  2. Dielectric properties of human placenta, umbilical cord and amniotic fluid

    Science.gov (United States)

    Peyman, A.; Gabriel, C.; Benedickter, H. R.; Fröhlich, J.

    2011-04-01

    The dielectric properties of freshly delivered human placenta, umbilical cord and amniotic fluid have been acquired at 37 °C and in the frequency range of 200 MHz-10 GHz. The experimental data were fitted to a Cole-Cole expression. The results show that dielectric properties of the umbilical cord are significantly higher than placenta due to the presence of high water content Wharton's jelly. The results also demonstrate large differences in the dielectric properties of amniotic and cerebrospinal fluids. The data presented can be used in numerical simulations of the exposure of pregnant women to electromagnetic fields.

  3. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

    Institute of Scientific and Technical Information of China (English)

    Chang Dong LI; Wei Yuan ZHANG; He Lian LI; Xiao Xia JIANG; Yi ZHANG; Pei Hsien TANG; Ning MAO

    2005-01-01

    Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium.The homogenous layer of adherent cells exhibited a typical fibroblastlike morphology,a large expansive potential,and cell cycle characteristics including a subset of quiescent cells.In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic,osteogenic and chondrogenic lineages.Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells,which uniformly expressed CD29,CD44,CD73,CD 105,CD166,laminin,fibronectin and vimentin while being negative for expression of CD31,CD34,CD45 and α-smooth muscle actin.Most importantly,immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-Ⅰ),but they did not express MHC-Ⅱ molecules.Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli.This strongly implies that they may have potential application in allograft transplantation.Since placenta and UCB are homogeneous,the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.

  4. Mercury concentrations in human placenta, umbilical cord, cord blood and amniotic fluid and their relations with body parameters of newborns.

    Science.gov (United States)

    Kozikowska, Iwona; Binkowski, Łukasz J; Szczepańska, Katarzyna; Sławska, Helena; Miszczuk, Katarzyna; Śliwińska, Magdalena; Łaciak, Tomasz; Stawarz, Robert

    2013-11-01

    Studies were conducted on samples taken from giving birth women (n = 40) living in Poland, representing three age groups: 19-25, 26-30 and 31-38 years old. Mercury concentrations were measured with CV-AAS in placenta, umbilical cord, cord blood and amniotic fluid. The placentas weight did not exceed the 750 g value and was heavier than 310 g. Mean values of Hg concentrations in blood, placenta and umbilical cord were similar (c.a. 9 μg/g). High levels of mercury were noted in cord blood which in 75% of all observations exceeded (up to 17 μg/L) the safe dose set by US EPA (5.8 μg/L). No statistically significant differences in medium level of Hg in all the studied tissues among age groups of women were observed. Positive correlations between Hg concentrations in placenta and umbilical cord and cord blood were revealed as well as some negative ones between mercury concentrations and pregnancy parameters. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood

    DEFF Research Database (Denmark)

    Mose, Tina; Mortensen, Gerda K; Hedegaard, Morten;

    2006-01-01

    Fetal exposure to phthalates may be associated with adverse reproductive effects, including cryptorchidism and decreased semen quality. Information about human placental transfer is needed to qualify the hypotheses. A dual recirculating placenta perfusion system to monitor concentrations of eight...... phthalate monoesters in fetal and maternal perfusates was established. In addition to perfusate background measures of phthalate monoesters, the concentrations in umbilical cord plasma and placenta tissue were measured. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), monobutyl phthalate (m...

  6. Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Zhi Li; Wei Zhao; Wei Liu; Ye Zhou; Jingqiao Jia; Lifeng Yang

    2014-01-01

    Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the ifeld of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the resto-ration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

  7. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells

    Institute of Scientific and Technical Information of China (English)

    YiZhanga; ChangdongLi; XiaoxiaJiang; ShuangxiZhang; YingWu; BingLiu; PeihsienTang; NingMao

    2005-01-01

    Objective. Allogeneic transplantation with umbilical cord blood (UCB) in adult recipients is limited mainly by a low CD34+ cell dose. To overcome this shortcoming, human placenta as a novel source of human mesenchymal progenitor cell (MPC) was incorporated in an attempt to expand CD34+ ceils from UCB in vitro.Materials and Methods. Human placenta MPC was isolated and characterized by morphologic,immunophenotypical, and functional analysis. UCB CD34+ cells were expanded by coculturewith placeutal MPC. Suitable aliquots of cells were used to monitor cell production, elonogenie activity, and tong-term culture-initiating culture (LTC-IC) output. Finally, the immunoregulatory effect of placental MPC was evaluated by T-cell proliferation assay.Results. In its undifferentiated state, placental MPC displayed fibroblastoid morphology; was CD73, CD105, CD29, CD44, HLA-ABC, and CD166 positive; produced fibronectin, laminin,and vimentin; but was negative for CD14, CD31, CD34, CD45, HLA-DR, and α-smooth muscle actin. Functionally, it could be induced into adipocytes, osteocytes, and chondrocytes.In vitro expansion of UCB hematopoietic cells, when cocultured with placental MPC in the presence of eytokines, was significantly enhanced: CD34+ cells by 14.89±2.32 fold; colonyforming cell (CFC) by 36.73±5.79 told; and LTC-IC by 7.43±2.66 fold. Moreover, placental MPC could suppress T-cell proliferation induced by cellular stimuli.Conclusion. These results strongly suggest that human placental MPC may be a suitable feeder layer for expansion of hematopoietic progenitors from UCB in vitro.

  8. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue.

    Science.gov (United States)

    Heo, June Seok; Choi, Youjeong; Kim, Han-Soo; Kim, Hyun Ok

    2016-01-01

    Mesenchymal stem cells (MSCs) are clinically useful due to their capacity for self-renewal, their immunomodulatory properties and tissue regenerative potential. These cells can be isolated from various tissues and exhibit different potential for clinical applications according to their origin, and thus comparative studies on MSCs from different tissues are essential. In this study, we investigated the immunophenotype, proliferative potential, multilineage differentiation and immunomodulatory capacity of MSCs derived from different tissue sources, namely bone marrow, adipose tissue, the placenta and umbilical cord blood. The gene expression profiles of stemness-related genes [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box (SOX)2, MYC, Krüppel-like factor 4 (KLF4), NANOG, LIN28 and REX1] and lineage‑related and differentiation stage-related genes [B4GALNT1 (GM2/GS2 synthase), inhibin, beta A (INHBA), distal-less homeobox 5 (DLX5), runt-related transcription factor 2 (RUNX2), proliferator‑activated receptor gamma (PPARG), CCAAT/enhancer-binding protein alpha (C/EBPA), bone morphogenetic protein 7 (BMP7) and SOX9] were compared using RT-PCR. No significant differences in growth rate, colony-forming efficiency and immunophenotype were observed. Our results demonstrated that MSCs derived from bone marrow and adipose tissue shared not only in vitro tri-lineage differentiation potential, but also gene expression profiles. While there was considerable inter-donor variation in DLX5 expression between MSCs derived from different tissues, its expression appears to be associated with the osteogenic potential of MSCs. Bone marrow-derived MSCs (BM-MSCs) significantly inhibited allogeneic T cell proliferation possibly via the high levels of the immunosuppressive cytokines, IL10 and TGFB1. Although MSCs derived from different tissues and fibroblasts share many characteristics, some of the marker genes, such as B4GALNT1 and DLX5 may be useful for

  9. Aflatoxin B1 transfer and metabolism in human placenta.

    Science.gov (United States)

    Partanen, Heidi A; El-Nezami, Hani S; Leppänen, Jukka M; Myllynen, Päivi K; Woodhouse, Heather J; Vähäkangas, Kirsi H

    2010-01-01

    Aflatoxin B1 (AFB1), a common dietary contaminant, is a major risk factor of hepatocellular carcinoma (HCC). Early onset of HCC in some countries in Africa and South-East Asia indicates the importance of early life exposure. Placenta is the primary route for various compounds, both nutrients and toxins, from the mother to the fetal circulation. Furthermore, placenta contains enzymes for xenobiotic metabolism. AFB1, AFB1-metabolites, and AFB1-albumin adducts have been detected in cord blood of babies after maternal exposure during pregnancy. However, the role that the placenta plays in the transfer and metabolism of AFB1 is not clear. In this study, placental transfer and metabolism of AFB1 were investigated in human placental perfusions and in in vitro studies. Eight human placentas were perfused with 0.5 or 5microM AFB1 for 2-4 h. In vitro incubations with placental microsomal and cytosolic proteins from eight additional placentas were also conducted. Our results from placental perfusions provide the first direct evidence of the actual transfer of AFB1 and its metabolism to aflatoxicol (AFL) by human placenta. In vitro incubations with placental cytosolic fraction confirmed the capacity of human placenta to form AFL. AFL was the only metabolite detected in both perfusions and in vitro incubations. Since AFL is less mutagenic, but putatively as carcinogenic as AFB1, the formation of AFL may not protect the fetus from the toxicity of AFB1.

  10. Autophagy in term normal human placentas.

    Science.gov (United States)

    Signorelli, P; Avagliano, L; Virgili, E; Gagliostro, V; Doi, P; Braidotti, P; Bulfamante, G P; Ghidoni, R; Marconi, A M

    2011-06-01

    Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

  11. Apoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord

    Directory of Open Access Journals (Sweden)

    Syeda H. Afroze

    2016-12-01

    Conclusions: Apoptotic and stress signaling are augmented in preE placenta and cord tissue that alter the intrauterine environment and activates the detrimental signaling that is transported to fetus.

  12. STUDY OF MORPHOLOGICAL VARIATIONS OF 50 PLACENTAE WITH UMBILICAL CORDS AND ITS DEVELOPMENTAL RELEVANCE

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    Asra Anjum

    2015-09-01

    Full Text Available Introduction: The word “Placenta” is a Latin word and the Greek equivalent word is “Plakons” which means “Flat cake on a plate”. The placenta is a complex multifunctional organ. It provides nutrition, gas exchange, waste removal, endocrine function and immune support. Placenta is a special circulating system to the developing foetus. Being an organ of vital importance for continuation of pregnancy and foetal nutrition it has evolved great interest among the anatomists, embryologists, pathologists and obstetricians. Materials and Methods: The study was done in 50 placentae which were collected from the department of Obstetrics and Gynaecology in collaboration with the department of Anatomy, Kamineni Institute of Medical Sciences, Narketpally, Nalgonda, Telangana, during the period of 2 years. The morphological variations of placenta, the size, shape, weight and attachment of umbilical cord with its blood vessels were observed, recorded and photographed. The prime objective of the study is to compare and evaluate the morphological alterations of placenta and umbilical cord in pregnancy. Results and Conclusion: In the current study, the majority of the placentae showed round shape, few placentae with oval and irregular and with an accessory lobe in single placenta. The current study also includes variations in insertion of umbilical cords was eccentric in majority, central, marginal and velamentous in a few. Pregnancy induced hypertension significantly affects the placenta by reducing weight and it does not have any significant effect on the shape of placenta, umbilical cord insertion and number of cotyledons on maternal surface. The placenta is the most accurate record of the infants prenatal experience.

  13. Velamentous and Furcate Cord Insertion with Placenta Accreta in an IVF Pregnancy with Unicornuate Uterus

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    Mehmet Tunç Canda

    2013-01-01

    Full Text Available Velamentous and furcate cord insertion with concomitant placenta accreta is a very rare and life-threatening event of pregnancy for both the mother and the fetus. Obstetricians should be cautious about umbilical cord insertion and placental adherence abnormalities in pregnancies conceived by assisted reproductive technologies (ART particularly in women with Müllerian anomalies.

  14. Endothelial and lipoprotein lipases in human and mouse placenta

    DEFF Research Database (Denmark)

    Lindegaard, Marie Louise Skakkebæk; Olivecrona, Gunilla; Christoffersen, Christina;

    2005-01-01

    Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin...... protein associated with both cell types. In mouse placentas, lack of LPL expression resulted in increased EL mRNA expression. These results suggest that the cellular expression of EL and LPL in human placenta is different. Nevertheless, the two lipases might have overlapping functions in the mouse...... placenta. Our data also suggest that the major portions of both proteins are stored in an inactive form in human term placenta....

  15. Modeling Oxygen Transport in the Human Placenta

    Science.gov (United States)

    Serov, Alexander; Filoche, Marcel; Salafia, Carolyn; Grebenkov, Denis

    Efficient functioning of the human placenta is crucial for the favorable pregnancy outcome. We construct a 3D model of oxygen transport in the placenta based on its histological cross-sections. The model accounts for both diffusion and convention of oxygen in the intervillous space and allows one to estimate oxygen uptake of a placentone. We demonstrate the existence of an optimal villi density maximizing the uptake and explain it as a trade-off between the incoming oxygen flow and the absorbing villous surface. Calculations performed for arbitrary shapes of fetal villi show that only two geometrical characteristics - villi density and the effective villi radius - are required to predict fetal oxygen uptake. Two combinations of physiological parameters that determine oxygen uptake are also identified: maximal oxygen inflow of a placentone and the Damköhler number. An automatic image analysis method is developed and applied to 22 healthy placental cross-sections demonstrating that villi density of a healthy human placenta lies within 10% of the optimal value, while overall geometry efficiency is rather low (around 30-40%). In a perspective, the model can constitute the base of a reliable tool of post partum oxygen exchange efficiency assessment in the human placenta. Also affiliated with Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.

  16. Transport of persistent organic pollutants across the human placenta.

    Science.gov (United States)

    Vizcaino, Esther; Grimalt, Joan O; Fernández-Somoano, Ana; Tardon, Adonina

    2014-04-01

    Prenatal life is the most sensitive stage of human development to environmental pollutants. Early exposure to persistent organic pollutants (POPs) may increase the risk of adverse health effects during childhood. The mechanisms of transference of POPs during pregnancy are still not well understood. The present study is aimed to investigate the transfer of POPs between mother and fetus. The concentrations of 14 organochlorine pesticides, 7 polychlorinated biphenyls (PCBs) and 14 polybromodiphenyl ether (PBDEs) congeners have been measured in 308 maternal serum samples, their respective umbilical cords and 50 placental tissues from a mother-infant cohort representative of Spanish general population. In general, the adjusted lipid-basis concentrations were higher in maternal serum than in cord serum and placenta. The concentrations of most pollutants between maternal serum and cord serum and between maternal serum and placenta were significantly correlated. These distributions were consistent with a predominant maternal source that transfers the pollutants into the placenta and the fetus. However, this distribution did not correspond to passive diffusion of these compounds between these tissues according to lipid content. The compounds more readily metabolized were higher in newborns, which suggest that differences in metabolic capabilities may be responsible of the observed variations in POP distributions between mother and newborns. Prenatal exposure to 4,4'-DDT and some PBDEs such as BDE 99 and BDE 209 is much higher than it could be anticipated from the composition of maternal serum. POP exposure assessment studies of newborns may overlook the effects of some of these pollutants if they only consider maternal determinations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Fibulin-5 expression in the human placenta.

    Science.gov (United States)

    Gauster, Martin; Berghold, Veronika M; Moser, Gerit; Orendi, Kristina; Siwetz, Monika; Huppertz, Berthold

    2011-02-01

    Fibulin-5 is a secreted extracellular matrix glycoprotein and displays a diverse panel of biological functions, which can be segregated into elastogenic as well as extra-elastogenic functions. While elastogenic functions of fibulin-5 include essential roles in early steps of elastic fibre assembly, extra-elastogenic functions are widespread. Depending on the cell type used, fibulin-5 mediates cell adherence via a subset of integrins, antagonizes angiogenesis and inhibits migration as well as proliferation of endothelial and smooth muscle cells. In this study, we focused on the spatiotemporal expression of fibulin-5 in the human placenta. With progressing gestation, placental fibulin-5 expression increased from first trimester towards term. At term, placental fibulin-5 mRNA expression is lower when compared with other well-vascularized organs such as lung, kidney, heart, uterus and testis. In first trimester, placenta immunohistochemistry localized fibulin-5 in villous cytotrophoblasts and extravillous cytotrophoblasts of the proximal cell column. In term placenta, fibulin-5 was detected in the endothelial basement membrane and adventitia-like regions of vessels in the chorionic plate and stem villi. Cell culture experiments with the villous trophoblast-derived cell line BeWo showed that fibulin-5 expression was downregulated during functional differentiation and intercellular fusion. Moreover, cultivation of BeWo cells under low oxygen conditions impaired intercellular fusion and upregulated fibulin-5 expression. The spatiotemporal shift from the trophoblast compartment in first trimester to the villous vasculature at term suggests a dual role of fibulin-5 in human placental development.

  18. The placenta in toxicology. Part IV : Battery of toxicological test systems based on human placenta

    NARCIS (Netherlands)

    Göhner, Claudia; Svensson-Arvelund, Judit; Pfarrer, Christiane; Häger, Jan-Dirk; Faas, Marijke; Ernerudh, Jan; Cline, J Mark; Dixon, Darlene; Buse, Eberhard; Markert, Udo R

    2014-01-01

    This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains a wide spectrum of cell types and tissues, such as trophoblast cells, immune cells, fibroblasts, stem cells, endothelial cells, ves

  19. Autophagy in the human placenta throughout gestation.

    Directory of Open Access Journals (Sweden)

    Tai-Ho Hung

    Full Text Available BACKGROUND: Autophagy has been reported to be essential for pre-implantation development and embryo survival. However, its role in placental development and regulation of autophagy during pregnancy remain unclear. The aims of this study were to (1 study autophagy by characterizing changes in levels of beclin-1, DRAM, and LC3B in human placenta throughout gestation; (2 determine whether autophagy is involved in regulation of trophoblast invasion in JEG-3 cells (a choriocarcinoma cell line; (3 examine the effects of reduced oxygen and glucose on the autophagic changes; and (4 investigate the effect of reoxygenation and supplementation of glucose after oxygen-glucose deprivation (OGD on the autophagic changes in primary cytotrophoblasts obtained from normal term pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 40 placental samples representing different gestational stages showed (1 no significant differences in beclin-1, DRAM, and LC3B-II levels in placentas between early and mid-gestation, and late gestation with vaginal delivery; (2 placentas from late gestation with cesarean section had lower levels of LC3B-II compared to early and mid-gestation, and late gestation with vaginal delivery; levels of DRAM were also lower compared to placentas from early and mid-gestation; and (3 using explant cultures, villous tissues from early and late gestation had similar rates of autophagic flux under physiological oxygen concentrations. Knockdown of BECN1, DRAM, and LC3B had no effects on viability and invasion activity of JEG-3 cells. On the other hand, OGD caused a significant increase in the levels of LC3B-II in primary cytotrophoblasts, while re-supplementation of oxygen and glucose reduced these changes. Furthermore, there were differential changes in levels of beclin-1, DRAM, and LC3B-II in response to changes in oxygen and glucose levels. CONCLUSIONS/SIGNIFICANCE: Our results indicate that autophagy is involved in development of the human

  20. Circadian Kisspeptin expression in human term placenta.

    Science.gov (United States)

    de Pedro, M A; Morán, J; Díaz, I; Murias, L; Fernández-Plaza, C; González, C; Díaz, E

    2015-11-01

    Kisspeptin is an essential gatekeeper of reproductive function. During pregnancy high circulating levels of kisspeptin have been described, however the clear role of this neuropeptide in pregnancy remains unknown. We tested the existence of rhythmic kisspeptin expression in human full-term placenta from healthy pregnant women at six different time points during the day. The data obtained by Western blotting were fitted to a mathematical model (Fourier series), demonstrating, for the first time, the existence of a circadian rhythm in placental kisspeptin expression.

  1. Characterization and partial purification of phospholipase D from human placenta

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Hansen, Harald S.

    1995-01-01

    We report the existence in the human placenta of a phosphatidylcholine- hydrolyzing phospholipase D (PLD) activity, which has been characterized and partially purified. Triton X-100 effectively solubilized PLD from the particulate fraction of human placenta in a dose-dependent manner. However....... The present results form the basis for further purification of a PLD from human tissue....

  2. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  3. Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

    National Research Council Canada - National Science Library

    Castaño, Erika; Caviedes, Lorena; Hirsch, Sandra; Llanos, Miguel; Iñiguez, Germán; Ronco, Ana María

    2017-01-01

    ... (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns...

  4. Adenyl cyclase in the human placenta.

    Science.gov (United States)

    Sato, K; Ryan, K J

    1971-09-21

    This study demonstrated that the human placenta possesses an adenyl cyclase system responsive to catecholamines and sodium flouride (NaF). 2.5 gm human term placentas were homogenized, centrifuged, washed, resuspended, and used as the enzyme system when placed with various agents. Incubations and the determination of adenosine 3', 5' monophosphate (cyclic AMP) formed were performed. Samples stimulated by .0001 M catecholamines (L-epinephrine or L-norepinephrine) or .01 M NaF had higher levels of cyclic AMP than the controls (p. 005 for catecholamine-treated samples and p. 001 for NaF-treated samples). A concentration of .0001 M L-epinephrine or L-norepinephrine appeared to be a maximum effective dose and .0000001 M a minimum. L=epinephrine was 10 times as effective in the stimulation as L-norepinephrine. With .0001 M, 499 and 439 pmoles/10 minutes per 25 mg of tissue was formed, whereas in the control (no added hormones) 256 pmoles/10 minutes were formed. 3.2% ethanol activated the system by a small amount (p.02). Propranolol alone did not appear to have any effect; however, the effect of .0001 M L-epinephrine was reduced by 95% in the presence of .00001 M propranolol. Propranolol had no effect on NaF-stimulated activity.

  5. Organochlorine pesticide residues in human breast milk and placenta in Tohoku, Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, K.; Suzuki, K.; Oka, T.; Sugawara, N.; Ohba, T.; Kameo, S.; Satoh, H. [Environmental Heath Sciences, Tohoku Univ. Graduate School of Medicine, Sendai (Japan); Nakamura, T.; Saitoh, Y. [Miyagi Prefectural Inst. of Piblic Health and Environment (Japan); Okamura, K. [Dept. of Obstetrics, Tohoku Univ. Graduate School of Medicine, Sendai (Japan)

    2004-09-15

    Recently, we have started a birth cohort study to examine the effects of exposure to persistent organochemical pollutants and heavy metals on neurodevelopment in Japanese children, The Tohoku Study of Child Development. In this cohort study, biological samples, including maternal peripheral blood, cord blood, placenta, cord tissue, and breast milk have been collected from more than six hundred mother-infant pairs for chemical determinations. The growth of infants has been monitored using neurodevelopmental tests, including the Brazelton Neonatal Behavioral Assessment Scale, the Bayley Scale of Infant Development, the Kyoto Scale of Psychological Development, and others. Exposures to dioxin and related compounds, polychlorinated biphenyls, methylmercury, and several heavy metals were assessed. Additionally, since perinatal exposure to organochlorine pesticides may affect the neurodevelopment of children, we examined the effects of those pesticides in the cohort study. In the present study, several organochlorine pesticides were analyzed in human breast milk and placenta from 20 mothers to identify the major pesticide compounds found in the cohort subjects. The relationship between pesticides in breast milk and the placenta was analyzed to examine the utilization of the placenta as the material for exposure assessment. Some information regarding the factors affecting the contamination of breast milk and the placenta with organochlorine pesticides are also discussed.

  6. Sonoembryological evaluations of the development of placenta previa and velamentous cord insertion.

    Science.gov (United States)

    Hasegawa, Junichi

    2015-01-01

    Longitudinal and cross-sectional investigations using ultrasound examinations during pregnancy can be used to clarify the mechanisms and pathophysiology of abnormal fetal and placental development. Such sonoembryological assessments are useful as a method for clarifying the etiology of disease. In the present review, we describe current knowledge based on our experience with applying sonoembryological methods to determine the developmental mechanisms of placenta previa and velamentous cord insertion.

  7. Anthroposophic lifestyle influences the concentration of metals in placenta and cord blood

    Energy Technology Data Exchange (ETDEWEB)

    Fagerstedt, Sara [The Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm (Sweden); Kippler, Maria [Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm (Sweden); Scheynius, Annika; Gutzeit, Cindy [Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet and University Hospital, Stockholm (Sweden); Mie, Axel [The Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm (Sweden); Alm, Johan [The Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm (Sweden); Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm (Sweden); Vahter, Marie, E-mail: marie.vahter@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm (Sweden)

    2015-01-15

    Allergic diseases develop in genetically susceptible individuals in a complex interplay with the environment, usually early in life. We have previously shown that the anthroposophic lifestyle is associated with reduced risk of allergic disease in children, but details on the influencing environmental factors are largely unknown. This study aims to elucidate if anthroposophic lifestyle influences fetal exposure to selected toxic and essential elements. Randomly selected non-smoking mothers with (n=40) and without (n=40) anthroposophic lifestyle from the prospective birth cohort ALADDIN were included. Concentrations of 12 toxic and essential elements were analyzed in full term placentas and in the erythrocyte fractions of maternal peripheral blood and of umbilical cord blood, using inductively coupled plasma mass spectrometry. Cadmium concentrations in maternal blood and placenta were significantly higher in mothers with an anthroposophic lifestyle (p<0.001), while concentrations in cord blood were generally low, irrespective of lifestyle. Cobalt concentrations were higher in both maternal blood, placenta and cord blood in the anthroposophic group. Lead concentrations were higher in maternal blood and cord blood, but not placenta, of mothers with anthroposophic lifestyle. Analysis of covariance, including lifestyle, parity, maternal age, gestational age, vegetarian diet, use of herbal medicine and occupation in the model, showed that mainly the anthroposophic lifestyle was significantly associated with cadmium concentrations. In conclusion, women with an anthroposophic lifestyle had higher concentrations of cadmium, cobalt and lead concentrations. Cadmium concentrations might have been influenced by a diet rich in vegetables and/or low iron status of the mothers. - Highlights: • Toxic elements in mother–newborn pairs in relation to anthroposophic lifestyle. • Anthroposophic lifestyle was associated with higher levels of cadmium, cobalt and lead. • A diet rich

  8. Altered gene expression in human placenta after suspected preterm labour.

    Science.gov (United States)

    Oros, D; Strunk, M; Breton, P; Paules, C; Benito, R; Moreno, E; Garcés, M; Godino, J; Schoorlemmer, J

    2017-07-01

    Suspected preterm labour occurs in around 9% of pregnancies. However, almost two-thirds of women admitted for threatened preterm labour ultimately deliver at term and are considered risk-free for fetal development. We examined placental and umbilical cord blood samples from preterm or term deliveries after threatened preterm labour as well as term deliveries without threatened preterm labour. We quantitatively analysed the mRNA expression of inflammatory markers (IL6, IFNγ, and TNFα) and modulators of angiogenesis (FGF2, PGF, VEGFA, VEGFB, and VEGFR1). A total of 132 deliveries were analysed. Preterm delivery and term delivery after suspected preterm labour groups showed similar increases in TNFα expression compared with the term delivery control group in umbilical cord blood samples. Placental samples from preterm and term deliveries after suspected preterm labour exhibited significantly increased expression of TNFα and IL6 and decreased expression of IFNγ. Suspected preterm labour was also associated with altered expression of angiogenic factors, although not all differences reached statistical significance. We found gene expression patterns indicative of inflammation in human placentas after suspected preterm labour regardless of whether the deliveries occurred preterm or at term. Similarly, a trend towards altered expression of angiogeneic factors was not limited to preterm birth. These findings suggest that the biological mechanisms underlying threatened preterm labour affect pregnancies independently of gestational age at birth. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Kinetics of silica nanoparticles in the human placenta

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Mose, Tina; Maroun, Lisa Leth;

    2015-01-01

    choriocarcinoma cell line and the ex vivo perfused human placenta. Nanotoxicity in BeWo cells was examined by the MTT assay which demonstrated decreased cell viability at concentrations >100 µg/mL. In the placental perfusion experiments, antipyrine crossed the placenta rapidly, with a foetal:maternal ratio of 0...

  10. Optoacoustic measurements of human placenta and umbilical blood oxygenation

    Science.gov (United States)

    Nanovskaya, T. N.; Petrov, I. Y.; Petrov, Y.; Patrikeeva, S. L.; Ahmed, M. S.; Hankins, G. D. V.; Prough, D. S.; Esenaliev, R. O.

    2016-03-01

    Adequate oxygenation is essential for normal embryogenesis and fetal growth. Perturbations in the intrauterine oxidative environment during pregnancy are associated with several pathophysiological disorders such as pregnancy loss, preeclampsia, and intrauterine growth restriction. We proposed to use optoacoustic technology for monitoring placental and fetal umbilical blood oxygenation. In this work, we studied optoacoustic monitoring of oxygenation in placenta and umbilical cord blood ex vivo using technique of placenta perfusion. We used a medical grade, nearinfrared, tunable, optoacoustic system developed and built for oxygenation monitoring in blood vessels and in tissues. First, we calibrated the system for cord blood oxygenation measurements by using a CO-Oximeter (gold standard). Then we performed validation in cord blood circulating through the catheters localized on the fetal side of an isolated placental lobule. Finally, the oxygenation measurements were performed in the perfused placental tissue. To increase or decrease blood oxygenation, we used infusion of a gas mixture of 95% O2 + 5% CO2 and 95% N2 + 5% CO2, respectively. In placental tissue, up to four cycles of changes in oxygenation were performed. The optoacoustically measured oxygenation in circulating cord blood and in placental lobule closely correlated with the actual oxygenation data measured by CO-Oximeter. We plan to further test the placental and cord blood oxygenation monitoring with optoacoustics in animal and clinical studies.

  11. D2-40/podoplanin expression in the human placenta.

    Science.gov (United States)

    Wang, Y; Sun, J; Gu, Y; Zhao, S; Groome, L J; Alexander, J S

    2011-01-01

    Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.

  12. Placenta-on-a-chip: a novel platform to study the biology of the human placenta.

    Science.gov (United States)

    Lee, Ji Soo; Romero, Roberto; Han, Yu Mi; Kim, Hee Chan; Kim, Chong Jai; Hong, Joon-Seok; Huh, Dongeun

    2016-01-01

    Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was

  13. Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads.

    Science.gov (United States)

    Hurtado, Christine Waasdorp; Golden-Mason, Lucy; Brocato, Megan; Krull, Mona; Narkewicz, Michael R; Rosen, Hugo R

    2010-08-30

    Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.

  14. Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads.

    Directory of Open Access Journals (Sweden)

    Christine Waasdorp Hurtado

    Full Text Available Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6% is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44 on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.

  15. Expression and tissue localization of collectin placenta 1 (CL-P1, SRCL) in human tissues

    DEFF Research Database (Denmark)

    Sellman, Lana; Skjødt, Karsten; Nielsen, Ole;

    2008-01-01

    cells. It binds via its lectin domain to desialyated Lewis X containing glycoproteins and it is able to facilitate internalization of bound ligands. Via positively charged residues in the collagen-like region it binds to negatively charged components of microbial membranes. It has previously been......-like and stromal cells of the tonsils. By real-time RT-PCR we verified that the placenta is also the main organ of CL-P1 synthesis. The only source of endothelial cells whereto CL-P1 associates are umbilical cord vein endothelial cells (human umbilical vein endothelial cells, HUVEC). In vitro cultured HUVECs...

  16. Estimation of the total number of mast cells in the human umbilical cord. A methodological study

    DEFF Research Database (Denmark)

    Engberg Damsgaard, T M; Windelborg Nielsen, B; Sørensen, Flemming Brandt

    1992-01-01

    The aim of the present study was to estimate the total number of mast cells in the human umbilical cord. Using 50 microns-thick paraffin sections, made from a systematic random sample of umbilical cord, the total number of mast cells per cord was estimated using a combination of the optical...... disector and fractionated sampling. The mast cell of the human umbilical cord was found in Wharton's jelly, most frequently in close proximity to the three blood vessels. No consistent pattern of variation in mast cell numbers from the fetal end of the umbilical cord towards the placenta was seen....... The total number of mast cells found in the umbilical cord was 5,200,000 (median), range 2,800,000-16,800,000 (n = 7), that is 156,000 mast cells per gram umbilical cord (median), range 48,000-267,000. Thus, the umbilical cord constitutes an adequate source of mast cells for further investigation...

  17. Purification and characterization of a soluble calnexin from human placenta

    DEFF Research Database (Denmark)

    Olsen, Dorthe T; Peng, Li; Træholt, Sofie D;

    2013-01-01

    Calreticulin (Crt) and calnexin (Cnx) are homologous endoplasmic reticulum (ER) chaperones involved in protein folding and quality control. Crt is a soluble ER luminal Mr 46 kDa protein and Cnx is a Mr 67kDa ER membrane protein. During purification of Crt from human placenta a soluble form of Cnx...

  18. Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China.

    Science.gov (United States)

    Zhang, Xiaolan; Li, Xiaojing; Jing, Ye; Fang, Xiangming; Zhang, Xinyu; Lei, Bingli; Yu, Yingxin

    2017-03-01

    Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a high-priority public health concern. However, maternal to fetal transplacental transfer of PAHs has not been systematically studied. To investigate the transplacental transfer of PAHs from mother to fetus and determine the influence of lipophilicity (octanol-water partition coefficient, KOW) on transfer process, in the present study, we measured the concentrations of 15 PAHs in 95 paired maternal and umbilical cord serum, and placenta samples (in total 285 samples) collected in Shanghai, China. The average concentration of total PAHs was the highest in maternal serums (1290 ng g(-1) lipid), followed by umbilical cord serums (1150 ng g(-1) lipid). The value was the lowest in placenta samples (673 ng g(-1) lipid). Low molecular weight PAHs were the predominant compounds in the three matrices. Increases in fish and meat consumption did not lead to increases in maternal PAH levels, and no obvious gender differences in umbilical cord serums were observed. The widespread presence of PAHs in umbilical cord serums indicated the occurrence of transplacental transfer. The ratios of PAH concentrations in umbilical cord serum to those in maternal serum (F/M) and the concentrations in placenta to those in maternal serum (P/M) of paired samples were analyzed to characterize the transfer process of individual PAHs. Most F/M ratios on lipid basis were close to one (range: 0.79 to 1.36), which suggested that passive diffusion may control the transplacental transfer of PAHs from maternal serum to the fetal circulation. The P/M and F/M values calculated on lipid basis showed that PAHs with lower KOW were more likely to transfer from mother to fetus via the placenta. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Analytical theory of oxygen transport in the human placenta.

    Science.gov (United States)

    Serov, A S; Salafia, C M; Filoche, M; Grebenkov, D S

    2015-03-07

    We propose an analytical approach to solving the diffusion-convection equations governing oxygen transport in the human placenta. We show that only two geometrical characteristics of a placental cross-section, villi density and the effective villi radius, are needed to predict fetal oxygen uptake. We also identify two combinations of physiological parameters that determine oxygen uptake in a given placenta: (i) the maximal oxygen inflow of a placentone if there were no tissue blocking the flow and (ii) the ratio of transit time of maternal blood through the intervillous space to oxygen extraction time. We derive analytical formulas for fast and simple calculation of oxygen uptake and provide two diagrams of efficiency of oxygen transport in an arbitrary placental cross-section. We finally show that artificial perfusion experiments with no-hemoglobin blood tend to give a two-orders-of-magnitude underestimation of the in vivo oxygen uptake and that the optimal geometry for such setup alters significantly. The theory allows one to adjust the results of artificial placenta perfusion experiments to account for oxygen-hemoglobin dissociation. Combined with image analysis techniques, the presented model can give an easy-to-use tool for prediction of the human placenta efficiency.

  20. Kinetics of gold nanoparticles in the human placenta.

    Science.gov (United States)

    Myllynen, Päivi K; Loughran, Michael J; Howard, C Vyvyan; Sormunen, Raija; Walsh, Adrian A; Vähäkangas, Kirsi H

    2008-10-01

    We studied the transfer of PEGylated gold nanoparticles through perfused human placenta. In 'once-through' perfusions using 15 and 30nm nanoparticles both maternal and fetal outflows were collected. Recirculating perfusions using 10 or 15nm nanoparticles lasted 6h. The gold concentration in samples was analysed on ICP-MS. The reference compound antipyrine crossed the placenta rapidly, as expected. In open perfusions nanoparticles were detected in maternal but not in fetal outflow, suggesting the lack of placental transfer. During 6h re-circulating perfusions, no particles were detected in fetal circulation. Using transmission electron microscopy (TEM) and silver enhancement, nanoparticles could be visualized in the placental tissue mainly in the trophoblastic cell layer. In in vitro experiments, nanoparticles were taken up by BeWo choriocarcinoma cells and retained inside the cells for an extended period of 48h. In conclusion, PEGylated gold nanoparticles of the size 10-30nm did not cross the perfused human placenta in detectable amounts into the fetal circulation within 6h. Whether PEGylated gold nanoparticles eventually are able to cross placenta and whether nanoparticles affect placental functions needs to be further studied.

  1. In Vitro Differentiation Potential of Human Placenta Derived Cells into Skin Cells

    Directory of Open Access Journals (Sweden)

    Ruhma Mahmood

    2015-01-01

    Full Text Available Skin autografting is the most viable and aesthetic technique for treatment of extensive burns; however, this practice has potential limitations. Harvesting cells from neonatal sources (such as placental tissue is a simple, inexpensive, and noninvasive procedure. In the current study authors sought to evaluate in vitro potential of human placenta derived stem cells to develop into skin-like cells. After extensive washing, amniotic membrane and umbilical cord tissue were separated to harvest amniotic epithelial cells (AECs and umbilical cord mesenchymal stem cells (UC-MSCs, respectively. Both types of cells were characterized for the expression of embryonic lineage markers and their growth characteristics were determined. AECs and UC-MSCs were induced to differentiate into keratinocytes-like and dermal fibroblasts-like cells, respectively. After induction, morphological changes were detected by microscopy. The differentiation potential was further assessed using immunostaining and RT-PCR analyses. AECs were positive for cytokeratins and E-Cadherin while UC-MSCs were positive for fibroblast specific makers. AECs differentiated into keratinocytes-like cells showed positive expression of keratinocyte specific cytokeratins, involucrin, and loricrin. UC-MSCs differentiated into dermal fibroblast-like cells indicated expression of collagen type 3, desmin, FGF-7, fibroblast activation protein alpha, procollagen-1, and vimentin. In conclusion, placenta is a potential source of cells to develop into skin-like cells.

  2. Endothelial and lipoprotein lipases in human and mouse placenta

    DEFF Research Database (Denmark)

    Lindegaard, Marie L S; Olivecrona, Gunilla; Christoffersen, Christina;

    2005-01-01

    Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin......-Sepharose affinity chromatography, the EL protein eluted as a single peak without detectable phospholipid or triglyceride (TG) lipase activity. The major portion of LPL protein eluted slightly after EL. This peak also had no lipase activity and most likely contained monomeric LPL. Fractions eluting at a higher Na......Cl concentration contained small amounts of LPL protein (most likely dimeric LPL) and had substantial TG lipase activity. In situ hybridization studies showed EL mRNA expression in syncytiotrophoblasts and endothelial cells and LPL mRNA in syncytiotrophoblasts. In contrast, immunohistochemistry showed EL and LPL...

  3. Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Xiaokui eZhang

    2013-05-01

    Full Text Available Recent clinical studies suggest that adoptive transfer of donor-derived natural killer (NK cells may improve clinical outcome in hematological malignancies and some solid tumors by direct antitumor effects as well as by reduction of graft versus host disease (GVHD. NK cells have also been shown to enhance transplant engraftment during allogeneic hematopoietic stem cell transplantation (HSCT for hematological malignancies. The limited ex vivo expansion potential of NK cells from peripheral blood (PB or umbilical cord blood (UCB has however restricted their therapeutic potential. Here we define methods to efficiently generate NK cells from donor matched, full-term human placenta perfusate (termed Human Placenta-Derived Stem Cell, HPDSC and UCB. Following isolation from cryopreserved donor-matched HPDSC and UCB units, CD56+CD3- placenta-derived NK cells, termed pNK cells, were expanded in culture for up to 3 weeks to yield an average of 1.2 billion cells per donor that were >80% CD56+CD3-, comparable to doses previously utilized in clinical applications. Ex vivo-expanded pNK cells exhibited a marked increase in anti-tumor cytolytic activity coinciding with the significantly increased expression of NKG2D, NKp46 and NKp44 (p < 0.001, p < 0.001, and p < 0.05, respectively. Strong cytolytic activity was observed against a wide range of tumor cell lines in vitro. pNK cells display a distinct microRNA (miRNA expression profile, immunophenotype and greater antitumor capacity in vitro compared to PB NK cells used in recent clinical trials. With further development, pNK may represent a novel and effective cellular immunotherapy for patients with high clinical needs and few other therapeutic options.

  4. Stereological Analysis of Human Placenta in Cases of Placenta Previa in Comparison with Normally Implanted Controls

    Science.gov (United States)

    Heidari, Zahra; Sakhavar, Nahid; Mahmoudzadeh-Sagheb, Hamidreza; Ezazi-Bojnourdi, Tahmine

    2015-01-01

    Background Placenta previa (PP) is an obstetric complication that can affect maternal and fetal morbidity and mortality. Its prevalence is rising due to cesarean sections. There is no quantitative data of placenta in PP. In this study, quantitative parameters of placenta in cases with PP in comparison with normally implanted controls were investigated. Methods In this quasi experimental study, placentas from pregnancies with PP and normally implanted controls (n = 10) were obtained from women who underwent cesarean section. Three full-thickness columns of each placenta were sampled using systematic uniform random sampling (SURS). Columns were cut into slices and slices were sectioned with 4 µm thickness. SURS selected sections were stained by Masson's trichrome. Stereological analysis was done on 8-10 SURS microscopic fields of each section. Absolute volume and volume density of chorionic villi, intervillous space, syncytiotrophoblast, fibrin and blood vessels in chorionic villi were estimated in both groups. Statistical analysis was done using Mann Whitney-U test and significant level was set at p placenta. These changes probably can be influential on the evolution and survival of fetus. PMID:25927025

  5. Location of the placenta or the umbilical cord insertion site in the lowest uterine segment is associated with low maternal blood pressure.

    Science.gov (United States)

    Hasegawa, J; Sekizawa, A; Farina, A; Nakamura, M; Matsuoka, R; Ichizuka, K; Okai, T

    2011-11-01

    To evaluate whether placental abnormalities and umbilical cord insertion site affect the occurrence of pre-eclampsia and maternal blood pressure. Case-control study. Showa University Hospital, Tokyo, Japan. A total of 5722 consecutive women who delivered singleton infants were included in the study. The associations of placental abnormalities, the location of the placenta, the location of the cord insertion site, and maternal background with the occurrence of pre-eclampsia and maternal blood pressure at the term of pregnancy were analysed. Pre-eclampsia and maternal blood pressure at the term of pregnancy. Pre-eclampsia was observed in 236 women (4.1%). Pre-eclampsia was frequently observed in women with placental form abnormalities (odds ratio 3.0) and infarction of the placenta (odds ratio 5.3). Pre-eclampsia was observed in 0 and 4.1% of women with and without placenta praevia, respectively (P = 0.004), and in 0 and 2.5% of women with and without low cord insertion during the first trimester, respectively (P = 0.018). After adjustment for confounding variables, the multivariate regression analyses revealed reductions of 8.4 and 5.0 mmHg in systolic and diastolic blood pressure, respectively, in women with placenta praevia compared with women without placenta praevia, and reductions of 4.3 and 3.1 mmHg in systolic and diastolic blood pressure, respectively, in women with low cord insertion during the first trimester compared with women without low cord insertion. Not only placenta praevia but also low cord insertion are associated with low frequencies of pre-eclampsia and low maternal blood pressure. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  6. Drug interactions at the human placenta: what is the evidence?

    Directory of Open Access Journals (Sweden)

    Miriam eRubinchik-Stern

    2012-07-01

    Full Text Available Pregnant women (and their fetuses are treated with a significant number of prescription and nonprescription medications. Interactions among those drugs may affect their efficacy and toxicity in both mother and fetus. Whereas interactions that result in altered drug concentrations in maternal plasma are detectable, those involving modulation of placental transfer mechanisms are rarely reflected by altered drug concentrations in maternal plasma. Therefore, they are often overlooked. Placental-mediated interactions are possible because the placenta is not only a passive diffusional barrier, but also expresses a variety of influx and efflux transporters and drug metabolizing enzymes. Current data on placental-mediated drug interactions are limited. In rodents, pharmacological or genetic manipulations of placental transporters significantly affect fetal drug exposure. In contrast, studies in human placentae suggest that the magnitude of such interactions is modest in most cases. Nevertheless, under certain circumstances, such interactions may be of clinical significance. This review describes currently known mechanisms of placental-mediated drug interactions and the potential implications of such interactions in humans. Better understanding of those mechanisms is important for minimizing fetal toxicity from drugs while improving their efficacy when directed to treat the fetus.

  7. STUDY OF MORPHOLOGICAL VARIATIONS OF 50 PLACENTAE WITH UMBILICAL CORDS AND ITS DEVELOPMENTAL RELEVANCE

    OpenAIRE

    Asra Anjum; D.Suseelamma; S. Saritha; T V Ramani; D. Nagajyothi

    2015-01-01

    Introduction: The word “Placenta” is a Latin word and the Greek equivalent word is “Plakons” which means “Flat cake on a plate”. The placenta is a complex multifunctional organ. It provides nutrition, gas exchange, waste removal, endocrine function and immune support. Placenta is a special circulating system to the developing foetus. Being an organ of vital importance for continuation of pregnancy and foetal nutrition it has evolved great interest among the anatomists, embryologists, patholog...

  8. Placenta Maps: In Utero Placental Health Assessment of the Human Fetus.

    Science.gov (United States)

    Miao, Haichao; Mistelbauer, Gabriel; Karimov, Alexey; Alansary, Amir; Davidson, Alice; Lloyd, David; Damodaram, Mellisa; Story, Lisa; Hutter, Jana; Hajnal, Joseph; Rutherford, Mary; Preim, Bernhard; Kainz, Bernhard; Groller, M Eduard

    2017-02-24

    The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using ultrasound (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. Magnetic resonance imaging (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.

  9. Glucose metabolism in cultured trophoblasts from human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H. (Washington Univ., St. Louis, MO (United States))

    1990-02-26

    The development of appropriate placental trophoblast isolation and culture techniques enables the study of pathways of glucose utilization by this important cell layer in vitro. Trophoblasts from normal term placentas were isolated and cultured 24 hours and 72 hours in uncoated polystyrene culture tubes or tubes previously coated with a fibrin matrix. Trophoblasts cultured on fibrin are morphologically distinct from those cultured on plastic or other matrices and generally resemble in vivo syncytium. Cells were incubated up to 3 hours with {sup 14}C-labeled glucose and reactions were stopped by addition of perchloric acid. {sup 14}CO{sub 2} production by trophoblasts increased linearly with time however the largest accumulation of label was in organic acids. Trophoblasts cultured in absence of fibrin utilized more glucose and accumulated more {sup 14}C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO{sub 2} by the phosphogluconate (PG) pathway was estimated from specific yields of {sup 14}CO{sub 2} from (1-{sup 14}C)-D-glucose and (6-{sup 14}C)-D-glucose. Approximately 6% of glucose oxidation was by the PG pathway when cells were cultured on fibrin compared to approximately 1% by cells cultured in the absence of fibrin. The presence of a fibrin growth matrix appears to modulate the metabolism of glucose by trophoblast from human placenta in vitro.

  10. Expression of the Thomsen-Friedenreich (TF) tumor antigen in human abort placentas.

    Science.gov (United States)

    Richter, D U; Jeschke, U; Bergemann, C; Makovitzky, J; Lüthen, F; Karsten, U; Briese, V

    2005-01-01

    The Thomsen-Friedenreich antigen (TF), or more precisely epitope, has been known as a pancarcinoma antigen. It consists of galactose-beta1-3-N-acetylgalactose. We have already described the expression of TF in the normal placenta. TF is expressed by the syncytium and by extravillous trophoblast cells. In this study, we investigated the expression of TF in the abort placenta. Frozen samples of human abort placentas (12 placentas), obtained from the first and second trimesters of pregnancy and, for comparison, samples of normal placentas (17 placentas) from the first, second and third trimesters of pregnancy, were used. Expression of TF was investigated by immunohistochemical methods. For identification of TF-positive cells in abort placentas, immunofluorescence methods were used. Evaluation of simple and double immunofluorescence was performed on a laser scanning microscope. Furthermore, we isolated trophoblast cells from first and third trimester placentas and evaluated cytokeratin 7 and Muc1 expression by immunofluorescence methods. We observed expression of TF antigen in the syncytiotrophoblasts layer of the placenta in all three trimesters of pregnancy in normal and abort placentas evaluated by immunohistochemical methods. There was no expression of TF antigen in the decidua of abort placentas. Immunofluorescence double staining of TF antigen and cytokeratin 7 showed reduced expression of both antigens in the abort decidua and co-expression of both antigens in the syncytiotrophoblast layer of normal and abort placentas. TF expression in the syncytiotrophoblast was reduced in abort placentas. In the isolated trophoblast cells, no TF expression was found, however, Muc1 expression was visualized. Expression of TF antigen was reduced in the first and second trimester abort decidua compared to the normal decidua during the same time of pregnancy. TF antigen was restricted to the syncytiotrophoblast and extravillous trophoblast cells in the decidua. Abort placentas

  11. Barrier Capacity of Human Placenta for Nanosized Materials

    Science.gov (United States)

    Wick, Peter; Malek, Antoine; Manser, Pius; Meili, Danielle; Maeder-Althaus, Xenia; Diener, Liliane; Diener, Pierre-Andre; Zisch, Andreas; Krug, Harald F.; von Mandach, Ursula

    2010-01-01

    Background Humans have been exposed to fine and ultrafine particles throughout their history. Since the Industrial Revolution, sources, doses, and types of nanoparticles have changed dramatically. In the last decade, the rapidly developing field of nanotechnology has led to an increase of engineered nanoparticles with novel physical and chemical properties. Regardless of whether this exposure is unintended or not, a careful assessment of possible adverse effects is needed. A large number of projects have been carried out to assess the consequences of combustion-derived or engineered nanoparticle exposure on human health. In recent years there has been a growing concern about the possible health influence of exposure to air pollutants during pregnancy, hence an implicit concern about potential risk for nanoparticle exposure in utero. Previous work has not addressed the question of whether nanoparticles may cross the placenta. Objective In this study we investigated whether particles can cross the placental barrier and affect the fetus. Methods We used the ex vivo human placental perfusion model to investigate whether nanoparticles can cross this barrier and whether this process is size dependent. Fluorescently labeled polystyrene beads with diameters of 50, 80, 240, and 500 nm were chosen as model particles. Results We showed that fluorescent polystyrene particles with diameter up to 240 nm were taken up by the placenta and were able to cross the placental barrier without affecting the viability of the placental explant. Conclusions The findings suggest that nanomaterials have the potential for transplacental transfer and underscore the need for further nanotoxicologic studies on this important organ system. PMID:20064770

  12. Purification and characterization of a soluble calnexin from human placenta.

    Science.gov (United States)

    Olsen, Dorthe T; Peng, Li; Træholt, Sofie D; Duus, Karen; Højrup, Peter; Houen, Gunnar

    2013-11-01

    Calreticulin (Crt) and calnexin (Cnx) are homologous endoplasmic reticulum (ER) chaperones involved in protein folding and quality control. Crt is a soluble ER luminal Mr 46 kDa protein and Cnx is a Mr 67kDa ER membrane protein. During purification of Crt from human placenta a soluble form of Cnx (sCnx) was consistently identified in a separate ion exchange chromatography peak. The sCnx was further purified and characterised. This showed that the protein had been cleaved after residue 472 (between Gln and Met), thus liberating it from the transmembrane and cytoplasmic parts of Cnx. The extraction and initial purification steps were carried out in the presence of protease inhibitors, thus ruling out that the cleavage was an artefact of the isolation procedure. This indicates that sCnx may have a physiological chaperone function similar to that of Crt.

  13. GLUT12 expression in human placenta in first trimester and term

    NARCIS (Netherlands)

    Gude, NM; Stevenson, JL; Rogers, S; Best, JD; Kalionis, B; Erwich, JJHM; Timmer, A; King, RG

    2003-01-01

    The aim of this study was to characterize the expression of a novel glucose transporter protein GLUT12 in human placenta. GLUT12 mRNA expression was identified by RT-PCR in extracts from five normal term placentae and in extracts from cultured cells of the JAR, JEG-3 and HTR-8Svneo cell lines. In fu

  14. mRNA related to insulin family in human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Younes, M.A.; D' Agostino, J.B.; Frazier, M.L.; Besch, P.K.

    1986-03-01

    The authors have previously reported that human term placenta contains mRNA displaying sequence homology to a rat preproinsulin I cDNA clone (p119). When placental poly(A/sup +/) RNA was analyzed for homology to p119 by RNA/DNA blot hybridization, prominent hybridization was observed which was found by densitometric analysis to be three-fold higher than control. To further characterize this insulin-like message, a cDNA library was generated (approx.7000 transformants) using normal term cesarean-sectioned tissue to prepare placental poly(A/sup +/) RNA templates. Five hundred transformants were initially screened by colony hybridization using a /sup 32/P-labeled rat preproinsulin I cDNA as probe. Of the ten initial positives obtained, three were found to be true positives based on Southern hybridization analyses of the recombinant plasmids. Using Taq I digested pBr322 as a size marker, the cDNAs were found to be approximately 300 bp in length. Preliminary DNA sequencing using the Sanger dideoxy chain termination method has revealed that one of these clones displays significant homology to the 5' region of human insulin-like growth factors I and II.

  15. A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment

    DEFF Research Database (Denmark)

    Muoth, Carina; Wichser, Adrian; Monopoli, Marco;

    2016-01-01

    and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized...... and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher...

  16. Estimation of the total number of mast cells in the human umbilical cord. A methodological study.

    Science.gov (United States)

    Engberg Damsgaard, T M; Windelborg Nielsen, B; Sørensen, F B; Henriques, U; Schiøtz, P O

    1992-09-01

    The aim of the present study was to estimate the total number of mast cells in the human umbilical cord. Using 50 microns-thick paraffin sections, made from a systematic random sample of umbilical cord, the total number of mast cells per cord was estimated using a combination of the optical disector and fractionated sampling. The mast cell of the human umbilical cord was found in Wharton's jelly, most frequently in close proximity to the three blood vessels. No consistent pattern of variation in mast cell numbers from the fetal end of the umbilical cord towards the placenta was seen. The total number of mast cells found in the umbilical cord was 5,200,000 (median), range 2,800,000-16,800,000 (n = 7), that is 156,000 mast cells per gram umbilical cord (median), range 48,000-267,000. Thus, the umbilical cord constitutes an adequate source of mast cells for further investigation of these cells in the newborn, e.g. for describing their functional and secretory characteristics and possible clinical relevance in relation to the development of allergic, inflammatory and immunological diseases in infancy and childhood.

  17. A comprehensive analysis of the human placenta transcriptome.

    Science.gov (United States)

    Saben, J; Zhong, Y; McKelvey, S; Dajani, N K; Andres, A; Badger, T M; Gomez-Acevedo, H; Shankar, K

    2014-02-01

    As the conduit for nutrients and growth signals, the placenta is critical to establishing an environment sufficient for fetal growth and development. To better understand the mechanisms regulating placental development and gene expression, we characterized the transcriptome of term placenta from 20 healthy women with uncomplicated pregnancies using RNA-seq. To identify genes that were highly expressed and unique to the placenta we compared placental RNA-seq data to data from 7 other tissues (adipose, breast, hear, kidney, liver, lung, and smooth muscle) and identified several genes novel to placental biology (QSOX1, DLG5, and SEMA7A). Semi-quantitative RT-PCR confirmed the RNA-seq results and immunohistochemistry indicated these proteins were highly expressed in the placental syncytium. Additionally, we mined our RNA-seq data to map the relative expression of key developmental gene families (Fox, Sox, Gata, Tead, and Wnt) within the placenta. We identified FOXO4, GATA3, and WNT7A to be amongst the highest expressed members of these families. Overall, these findings provide a new reference for understanding of placental transcriptome and can aid in the identification of novel pathways regulating placenta physiology that may be dysregulated in placental disease.

  18. Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

    OpenAIRE

    Alwarfaly, Samy; Abdulsid, Akrem; Hanretty, Kevin; Lyall, Fiona

    2014-01-01

    Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON...

  19. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta

    OpenAIRE

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L.; Perdomo, Germán

    2013-01-01

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase...

  20. Human Placenta: a Source of Progenitor/Stem Cells?

    Directory of Open Access Journals (Sweden)

    Parolini O

    2006-01-01

    Full Text Available Regenerative medicine based on cell therapy and tissue engineering methodologies is a newly emerging, multidisciplinary field involving biology, medicine, and genetic manipulation. This type of therapy is aimed at maintaining, restoring, or enhancing tissue and organ function, and is intended to assist in the treatment of a number of human conditions which range in severity from chronic to life threatening. In diseases where tissue or organ function is compromised, stem cell research holds great promise for providing an efficient avenue for regenerative therapy. However, the application of this type of research to the treatment of human disease will not be possible until much more is known about the biological properties of all types of stem cells. In the context of disease treatment, decisions will need to be made as to which is the best type of stem cell to use. Whether it is better to identify a stem cell able to differentiate into all tissue and organ types as opposed to using committed, lineage-specific stem cells, or perhaps embryonic cells are better than adult-derived stem cells, as well as the possible clinical applications of these cells. For some time, these questions have not only required significant scientific and medical consideration, but have also posed important social and ethical questions. There is no doubt that stem cells hold great therapeutic potential, however there is still much research required before their use can be accepted as a valuable tool in disease treatment. In particular, it is necessary to identify a source of stem cells that is easily accessible, provides a high cell yield and for which cell recovery does not provoke serious ethical debate. The aim of this review is to consider and discuss the findings regarding a new source of "adult" stem cells isolated from human term placenta tissue. So far, the placental tissue has generally been discarded post partum, but it is now becoming recognised as a potential

  1. The human placenta--an alternative for studying foetal exposure

    DEFF Research Database (Denmark)

    Myren, Maja; Mose, Tina; Mathiesen, Line;

    2007-01-01

    , and though its main task is to act as a barrier and transport nutrients and oxygen to the foetus, many foreign compounds are transported across the placenta to some degree and may therefore influence the unborn child. Foetal exposures to environmental and medicinal products may have impact on the growth...

  2. The metallome of the human placenta in gestational diabetes mellitus.

    Science.gov (United States)

    Roverso, Marco; Berté, Chiara; Di Marco, Valerio; Lapolla, Annunziata; Badocco, Denis; Pastore, Paolo; Visentin, Silvia; Cosmi, Erich

    2015-07-01

    Obtaining the knowledge of the "omics" and therefore of the metallomics of gestational diabetes mellitus (GDM) appears to be a necessary task to obtain information about the molecular causes of this disease. In this study, the metallome of GDM and of other types of diabetes mellitus was first reviewed. The comparative analysis of the published data revealed that no GDM elemental markers could be identified with sufficient reliability in blood or in the other considered samples, with the partial exception of selenium. The placenta was chosen as an alternative target organ for the analysis of the GDM metallome. The full elemental average composition of 19 healthy placentas was obtained by ICP-MS. Analyses were then performed on 28 placentas from women affected by GDM. The statistical tests and the principal component analysis evidenced that cadmium was found in lower concentrations and selenium was found in higher concentrations in GDM placentas than in those of the control group. These results were interpreted in light of literature data, and they attract attention on two key elements for understanding the molecular pathways of GDM.

  3. Changes of Leptin Level in Serum, Cord Venous Blood and Placenta in Women with Gestational Diabetes Mellitus and Correlations with Insulin and C-Peptide

    Institute of Scientific and Technical Information of China (English)

    Jin-ming ZHU; Li SHI; Xiao-yuan LU; Rong-rong ZHANG; Min LI; Xiao-ning ZHANG

    2014-01-01

    ObjectiveTo investigate the changes of leptin levels in serum, cord venous blood and placenta and examine the possible relationships among them in women with gestational diabetes mellitus (GDM).Methods This case-control study was performed in 40 women with GDM and 40 normal women. The women with GDM received dietary advice, blood glucose monitoring and insulin treatment when necessary. Maternal serum and venous cord blood leptin, insulin and C-peptide levels were detected by ELISA. The expression level of leptin in placenta was measured by an immunohistochemical method. Results1. Leptin, insulin and C-peptide levels in serum of the women with GDM were significantly higher than those of the normal women (P<0.01,P<0.05, P<0.01). 2. Cord venous blood leptin and insulin in GDM group were significantly higher than in the normal group (P<0.01,P<0.05). No significant difference was found in cord venous blood C-peptide between two groups. 3. The expression of placenta leptin protein was significantly higher in GDM women than in normal women (P<0.01). There were positive correlations between placental leptin, cord venous leptin and insulin, birth weight, ponderal index in GDM women (r=0.37,P<0.05;r=0.39,P<0.05;r=0.53,P<0.01;r=0.54,P<0.01). However, there was no correlation between placental leptin and serum leptin.Conclusion The women with GDM and their fetuses suffer from hyperleptinaemia and hyperinsulinaemia. In the women with GDM, there was disorder in the interaction between leptin and insulin. The GDM women and their fetuses may be prone to insulin resistance and leptin resistance in late pregnancy.

  4. Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 1: physiology, function and sampling of placenta for elemental characterisation.

    Science.gov (United States)

    Iyengar, G V; Rapp, A

    2001-12-03

    Choice of specimen from human subjects for monitoring pollutants proven to be detrimental to human health depends on the criteria chosen, namely real-time monitoring (RTM) or long-term monitoring (LTM). Specimens such as whole blood, urine, saliva and breast milk are commonly used from living subjects for RTM of toxic metals. However, sampling blood requires an invasive procedure. On the other hand, hair (with some limitations), bone (especially for the assessment of bone seeking elements), adipose tissue (mainly for organic pollutants) and liver (for both organic and inorganic toxicants) are used as specimens for LTM. With the exception of hair, generally these specimens are obtained at post-mortem. In context of health-related biomonitoring, placenta as a specimen has not received as much attention as it deserves. It is a unique sample requiring no invasive procedure, and offers possibilities for RTM, in particular as a dual purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. Obtaining representative samples of placenta for elemental composition studies is a difficult task, because of heterogeneous mix of placental cells and decidual matter tainted with maternal and fetal blood. Therefore, the present sampling practices for placental tissue, and guidelines to safeguard the validity of the sampled material have been reviewed in part 1 with the following conclusions: medico-legal and ethical matters should be properly addressed before collecting the placenta; it is advisable to collect the entire placenta even if it includes the umbilical cord; further preparatory work is to be carried out in a clean laboratory and depends upon the purpose of the investigation; homogenising the entire sample may prove to be technically challenging but this step is crucial to obtain representative samples, handling the entire sample may be unavoidable; and an alternative method of procuring representative samples would require random

  5. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction.

    Science.gov (United States)

    Loubière, L S; Vasilopoulou, E; Bulmer, J N; Taylor, P M; Stieger, B; Verrey, F; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S-Y

    2010-04-01

    Thyroid hormones (TH) are important for the development of the human fetus and placenta from very early gestation. The transplacental passage of TH from mother to fetus and the supply of TH into trophoblasts require the expression of placental TH plasma membrane transporters. We describe the ontogeny of the TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 in a large series (n = 110) of normal human placentae across gestation and describe their expression changes with intrauterine fetal growth restriction (IUGR n = 22). Quantitative RT-PCR revealed that all the mRNAs encoding TH transporters are expressed in human placenta from 6 weeks gestation and throughout pregnancy. MCT8, MCT10, OATP1A2 and LAT1 mRNA expression increased with gestation. OATP4A1 and CD98 (LATs obligatory associated protein) mRNA expression reached a nadir in mid-gestation before increasing towards term. LAT2 mRNA expression did not alter throughout gestation. Immunohistochemistry localised MCT10 and OATP1A2 to villous cytotrophoblasts and syncytiotrophoblasts, and extravillous trophoblasts while OATP4A1 was preferentially expressed in the villous syncytiotrophoblasts. Whilst MCT8 protein expression was increased, MCT10 mRNA expression was decreased in placentae from IUGR pregnancies delivered in the early 3rd trimester compared to age matched appropriately grown for gestational age controls. No significant change was found in the mRNA expression of the other transporters with IUGR. In conclusion, several TH transporters are present in the human placenta from early 1st trimester with varying patterns of expression throughout gestation. Their coordinated effects may regulate both transplacental TH passage and TH supply to trophoblasts, which are critical for the normal development of the fetus and placenta. Increased MCT8 and decreased MCT10 expression within placentae of pregnancies complicated by IUGR may contribute to aberrant development of the fetoplacental unit.

  6. Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction.

    Science.gov (United States)

    Chan, S-Y; Franklyn, J A; Pemberton, H N; Bulmer, J N; Visser, T J; McCabe, C J; Kilby, M D

    2006-06-01

    Thyroid hormones (THs) are essential for normal fetal development, with even mild perturbation in maternal thyroid status in early pregnancy being associated with neurodevelopmental delay in children. Transplacental transfer of maternal THs is critical, with increasing evidence suggesting a role for 3,3',5-tri-iodothyronine (T3) in development and function of the placenta itself, as well as in development of the central nervous and other organ systems. Intrauterine growth restriction (IUGR) is associated with fetal hypothyroxinaemia, a factor that may contribute to neurodevelopmental delay. The recent description of monocarboxylate transporter 8 (MCT8) as a powerful and specific TH membrane transporter, and the association of MCT8 mutations with profound neurodevelopmental delay, led us to explore MCT8 expression in placenta. We describe the expression of MCT8 in normal human placenta throughout gestation, and in normal third-trimester placenta compared with that associated with IUGR using quantitative reverse transcriptase PCR. MCT8 mRNA was detected in placenta from early first trimester, with a significant increase with advancing gestation (P=0.007). In the early third trimester, MCT8 mRNA was increased in IUGR placenta compared with normal samples matched for gestational age (PMCT8 immunostaining was demonstrated in villous cytotrophoblast and syncytiotrophoblast as well as extravillous trophoblast cells from the first trimester onwards with increasingly widespread immunoreactivity seen with advancing gestation. In conclusion, expression of MCT8 in placenta from early gestation is compatible with an important role in TH transport during fetal development and a specific role in placental development. Altered expression in placenta associated with IUGR may reflect a compensatory mechanism attempting to increase T3 uptake by trophoblast cells.

  7. The Human Placenta Project: placental structure, development, and function in real time.

    Science.gov (United States)

    Guttmacher, A E; Maddox, Y T; Spong, C Y

    2014-05-01

    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time.

  8. The Human Placenta Project: Placental Structure, Development, and Function in Real Time

    Science.gov (United States)

    Guttmacher, Alan E.; Maddox, Yvonne T.; Spong, Catherine Y.

    2014-01-01

    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated “Human Placenta Project,” with the ultimate goal of understanding human placental structure, development, and function in real time. PMID:24661567

  9. Manufacturing and use of human placenta-derived mesenchymal stromal cells for phase I clinical trials: Establishment and evaluation of a protocol

    Directory of Open Access Journals (Sweden)

    Ilić Nina

    2014-01-01

    Full Text Available Background/Aim. Mesenchymal stromal cells (MSCs have been utilised in many clinical trials as an experimental treatment in numerous clinical settings. Bone marrow remains the traditional source tissue for MSCs but is relatively hard to access in large volumes. Alternatively, MSCs may be derived from other tissues including the placenta and adipose tissue. In an initial study no obvious differences in parameters such as cell surface phenotype, chemokine receptor display, mesodermal differentiation capacity or immunosuppressive ability, were detected when we compared human marrow derived- MSCs to human placenta-derived MSCs. The aim of this study was to establish and evaluate a protocol and related processes for preparation placenta-derived MSCs for early phase clinical trials. Methods. A full-term placenta was taken after delivery of the baby as a source of MSCs. Isolation, seeding, incubation, cryopreservation of human placentaderived MSCs and used production release criteria were in accordance with the complex regulatory requirements applicable to Code of Good Manufacturing Practice manufacturing of ex vivo expanded cells. Results. We established and evaluated instructions for MSCs preparation protocol and gave an overview of the three clinical areas application. In the first trial, MSCs were co-transplanted iv to patient receiving an allogeneic cord blood transplant as therapy for treatmentrefractory acute myeloid leukemia. In the second trial, MSCs were administered iv in the treatment of idiopathic pulmonary fibrosis and without serious adverse effects. In the third trial, MSCs were injected directly into the site of tendon damage using ultrasound guidance in the treatment of chronic refractory tendinopathy. Conclusion. Clinical trials using both allogeneic and autologous cells demonstrated MSCs to be safe. A described protocol for human placenta-derived MSCs is appropriate for use in a clinical setting, relatively inexpensive and can be

  10. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

    OpenAIRE

    Loubière, L S; Vasilopoulou, E.; Bulmer, J N; Taylor, P. M.; Stieger, B.; Verrey, F.; McCabe, C. J.; Franklyn, J.A.; Kilby, M. D.; Chan, S-Y

    2010-01-01

    Thyroid hormones (TH) are important for the development of the human fetus and placenta from very early gestation. The transplacental passage of TH from mother to fetus and the supply of TH into trophoblasts require the expression of placental TH plasma membrane transporters. We describe the ontogeny of the TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 in a large series (n = 110) of normal human placentae across gestation and describe their expression changes with intrauterine ...

  11. [Procedure for purifying RNA polymerase II from human placenta].

    Science.gov (United States)

    Kandyba, L V; Matsanova, V R; Shamovskiĭ, I V; Raĭt, V K

    1994-12-01

    DNA-dependent RNA polymerase IIB having a specific activity of 320 u./mg has been isolated from the term placenta homogenate using extraction performed at 4-6 degrees C in the presence of 75 mM ammonium sulfate and 1.5% nonidet P40, fractionation on DEAE-cellulose DE 23, desalting and heparin-agarose chromatography, resulting in 330-fold purification and a 18% yield. Technical details have been determined which are of crucial importance for reproducibility of affinity chromatography. The possibility of proteolysis of the IIc subunit during enzyme purification has been demonstrated.

  12. Levels of DDT and its metabolites in placenta, maternal and cord blood and their potential influence on neonatal anthropometric measures

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saleh, Iman, E-mail: iman@kfshrc.edu.sa [Environmental Health Section, Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh (Saudi Arabia); Al-Doush, Inaam; Alsabbaheen, Ammar [Environmental Health Section, Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh (Saudi Arabia); Mohamed, Gamal El Din [Biostatistics, Epidemiology and Scientific Computing Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh (Saudi Arabia); Rabbah, Abdullah [Department of Pediatrics, King Khalid Hospital, Al-Kharj (Saudi Arabia)

    2012-02-01

    Previous studies of in utero exposure to dichlorodiphenyltrichloroethane (DDT) have shown mixed results for the harmful effects on fetal growth and development. This cross-sectional study was designed to: (1) examine the extent of DDT exposure in 1578 women, aged 28.5 {+-} 6.0 who delivered between June 2005 and 2006 in the area of Al-Kharj, Saudi Arabia; and (2) assess its influence on neonatal anthropometric measurement of newly born babies. DDT and its metabolites, namely 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p Prime -DDE), 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane (p,p Prime -DDD) and 1,1,1-trichloro-2,2 Prime bis (p-chlorophenyl) ethane (p,p Prime -DDT) were measured in cord and maternal serum as well as placenta by Gas Chromatography coupled with an Electron Capture Detector (GC/ECD). p,p Prime -DDE was detected in 28.3% of cord and 54.4% of maternal serum, reflecting past exposure, whereas the p,p Prime -DDT was only found in 0.46% cord and 1.2% maternal samples. As expected the p,p Prime -DDE cord levels (0.197 {+-} 0.961 {mu}g/L) were 2.8 times lower than the maternal levels (0.551 {+-} 1.778 {mu}g/L), and both were significantly correlated (r = 0.517) suggesting its transplacental transfer. The picture was different in placental tissues. p,p Prime -DDE and p,p Prime -DDT were detected in 84% and 99% of placental tissues, with the highest p,p Prime -DDT in placental tissues (29.62 {+-} 158.282 Micro-Sign g/kg dry wt.) compare to p,p Prime -DDE (10.167 {+-} 18.851 {mu}g/kg dry wt.). In general, the presence of DDT metabolites in our participants indicates that these chemicals are still relevant despite the fact that they have been banned or restricted in the study area for many years. Our results support the view for an association between low in utero exposure to DDT and the anthropometric development of the fetus leading to a reduction in its head circumference, crown-heel length, birth weight and birth height. Since the reduction in these

  13. Impaired mitochondrial function in human placenta with increased maternal adiposity.

    Science.gov (United States)

    Mele, James; Muralimanoharan, Sribalasubashini; Maloyan, Alina; Myatt, Leslie

    2014-09-01

    The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18.5 to 45 following C-section at term with no labor. Increasing maternal adiposity was associated with excessive production of reactive oxygen species and a significant reduction in placental ATP levels in placentae with male and female fetuses. To explore the potential mechanism of placental mitochondrial dysfunction, levels of transcription factors regulating the expression of genes involved in electron transport and mitochondrial biogenesis were measured. Our in vitro studies showed significant reduction in mitochondrial respiration in cultured primary trophoblasts with increasing maternal obesity along with an abnormal metabolic flexibility of these cells. This reduction in placental mitochondrial respiration in pregnancies complicated by maternal obesity could compromise placental function and potentially underlie the increased susceptibility of these pregnancies to fetal demise in late gestation and to developmental programming.

  14. Comparison of mesenchymal stem cells from human placenta and bone marrow

    Institute of Scientific and Technical Information of China (English)

    张毅; 李长东; 江小霞; 李荷莲; 唐佩弦; 毛宁

    2004-01-01

    Background Nowadays bone marrow represents the main source of mesenchymal stem cells (MSCs). We identified a new population of MSCs derived from human placenta and compared its biological characterization with bone marrow derived MSCs.Methods Mononucleated cells (MNC) were isolated from the human placenta tissue perfusate by density gradient fractionation. Individual colonies were selected and cultured in tissue dishes. At the same time, human bone marrow derived MSCs were identified. Culture-expanded cells were characterized by immune phenotyping and cultured under conditions promoting differetiation to osteoblasts or adipocytes. The hematopoietic cytokines were assayed using reverse transcriptase polymerase chain reaction (RT-PCR). Results Human placental MSCs exhibited fibroblastoid morphology. Flow cytometric analyses showed that the placental MSC were CD29, CD44, CD73, CD105, CD166, HLA-ABC positive; but were negative for CD34, CD45, and HLA-DR. Functionally, they could be induced into adipocytes or osteocytes. Moreover, several hematopoietic cytokine mRNA was found in placenta-derived MSCs by RT-PCR analysis, including IL-6, M-CSF, Flt3-ligand and SCF. These results were consistent with the properties of bone marrow derived MSCs.Conclusion These observations implicate the postpartum human placenta as an important and novel source of multipotent stem cells that could potentially be used for investigating mesenchymal differentiation and regulation of hematopoiesis.

  15. Human endogenous retrovirus-FRD envelope protein (syncytin 2 expression in normal and trisomy 21-affected placenta

    Directory of Open Access Journals (Sweden)

    Handschuh Karen

    2008-01-01

    Full Text Available Abstract Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT. During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies.

  16. Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta

    Science.gov (United States)

    Malassiné, André; Frendo, Jean-Louis; Blaise, Sandra; Handschuh, Karen; Gerbaud, Pascale; Tsatsaris, Vassilis; Heidmann, Thierry; Evain-Brion, Danièle

    2008-01-01

    Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT). During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies. PMID:18215254

  17. Transplacental transfer of acrylamide and glycidamide are comparable to that of antipyrine in perfused human placenta.

    Science.gov (United States)

    Annola, Kirsi; Karttunen, Vesa; Keski-Rahkonen, Pekka; Myllynen, Päivi; Segerbäck, Dan; Heinonen, Seppo; Vähäkangas, Kirsi

    2008-11-10

    Most drugs can penetrate the placenta but there are only a few studies on placental transfer of environmental toxic compounds. In this study, we used dual recirculating human placental perfusion to determine the transfer rate through the placenta of a neurotoxic and carcinogenic compound found in food, acrylamide and its genotoxic metabolite glycidamide. Putative acrylamide metabolism into glycidamide during the 4-h perfusions and acrylamide-derived DNA adducts in placental DNA after perfusions were also analyzed. Placentas were collected immediately after delivery and kept physiologically functional as confirmed by antipyrine kinetics, glucose consumption and leak from fetal to maternal circulation. Acrylamide (5 or 10 microg/ml) or glycidamide (5 microg/ml), both with antipyrine (100 microg/ml), was added to maternal circulation. Acrylamide and glycidamide were analyzed in the perfusion medium by liquid chromatography/mass spectrometry. Acrylamide and glycidamide crossed the placenta from maternal to fetal circulation with similar kinetics to antipyrine, suggesting fetal exposure if the mother is exposed. The concentrations in maternal and fetal circulations equilibrated within 2h for both studied compounds and with both concentrations. Acrylamide metabolism into glycidamide was not detected during the 4-h perfusions. Moreover, DNA adducts were undetectable in the placentas after perfusions. However, fetuses may be exposed to glycidamide after maternal metabolism. Although not found in placental tissue after 4h of perfusion, it is possible that glycidamide adducts are formed in fetal DNA.

  18. Review: A high capacity of the human placenta for genetic and epigenetic variation: implications for assessing pregnancy outcome.

    Science.gov (United States)

    Yuen, R K C; Robinson, W P

    2011-03-01

    Genetic and epigenetic studies of the human placenta can help to clarify the underlying mechanisms of placenta-associated diseases. However, such studies have also revealed a considerable degree of within- and between-placenta variability, which can be attributed to a variety of influences. We illustrate the inherent heterogeneity in the placenta using examples from two types of studies: 1) chromosomal mosaicism and 2) DNA methylation variation. We discuss the factors that may influence the distribution of variation and how, understanding the source of this variation is important for interpreting data used to investigate and predict clinical outcomes.

  19. First isolation and molecular characterization of Toxoplasma gondii from a human placenta in Argentina.

    Science.gov (United States)

    Pardini, Lais; Carral, Liliana A; Bernstein, Mariana; Gos, María L; Olejnik, Patricia; Unzaga, Juan M; Kaufer, Federico J; Freuler, Cristina B; Durlach, Ricardo A; Venturini, María C

    2014-04-01

    Blood sample and placenta were taken from a 37-week pregnant woman; serologic results indicated acute toxoplasmosis. Placenta was inoculated into mice. Seropositive mice were sacrificed and tissue cysts from brain were inoculated into new mice. Specific DNA was detected by PCR, and the isolate was characterized as Type II by nPCR-RFLP for nSAG2, SAG3, BTUB, GRA6, c29-2, c22-8, L358, PK1 and Apico markers. This is the first isolation and molecular characterization of Toxoplasma gondii from humans in Argentina. © 2013.

  20. Alteration in Expression and Methylation of IGF2/H19 in Placenta and Umbilical Cord Blood Are Associated with Macrosomia Exposed to Intrauterine Hyperglycemia.

    Science.gov (United States)

    Su, Rina; Wang, Chen; Feng, Hui; Lin, Li; Liu, Xinyue; Wei, Yumei; Yang, Huixia

    2016-01-01

    Macrosomia is one of the most common complications in gestational diabetes mellitus. Insulin-like growth factor 2 and H19 are two of the imprinted candidate genes that are involved in fetal growth and development. Change in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 has been proved to be an early event related to the programming of metabolic profile, including macrosomia and small for gestational age in offspring. Here we hypothesize that alteration in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 is associated with macrosomia induced by intrauterine hyperglycemia. The expression of insulin-like growth factor 2 is significant higher in gestational diabetes mellitus group (GDM group) compared to normal glucose tolerance group (NGT group) both in umbilical cord blood and placenta, while the expression of H19 is significant lower in GDM group in umbilical cord blood. The expression of insulin-like growth factor 2 is significant higher in normal glucose tolerance with macrosomia group (NGT-M) compared to normal glucose tolerance with normal birthweight group (NGT-NBW group) both in placenta and umbilical cord blood. A model with interaction term of gene expression of IGF2 and H19 found that IGF2 and the joint action of IGF2 and H19 in placenta showed significantly relationship with GDM/NGT and GDM-NBW/NGT-NBW. A borderline significant association was seen among IGF2 and H19 in cord blood and GDM-M/NGT-M. The methylation level at different CpG sites of insulin-like growth factor 2 and H19 in umbilical cord blood was also significantly different among groups. Based on the multivariable linear regression analysis, the methylation of the insulin-like growth factor 2 / H19 is closely related to birth weight and intrauterine hyperglycemia. We confirmed the existence of alteration in DNA methylation in umbilical cord blood exposed to intrauterine hyperglycemia and reported a

  1. Alteration in Expression and Methylation of IGF2/H19 in Placenta and Umbilical Cord Blood Are Associated with Macrosomia Exposed to Intrauterine Hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Rina Su

    Full Text Available Macrosomia is one of the most common complications in gestational diabetes mellitus. Insulin-like growth factor 2 and H19 are two of the imprinted candidate genes that are involved in fetal growth and development. Change in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 has been proved to be an early event related to the programming of metabolic profile, including macrosomia and small for gestational age in offspring. Here we hypothesize that alteration in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 is associated with macrosomia induced by intrauterine hyperglycemia.The expression of insulin-like growth factor 2 is significant higher in gestational diabetes mellitus group (GDM group compared to normal glucose tolerance group (NGT group both in umbilical cord blood and placenta, while the expression of H19 is significant lower in GDM group in umbilical cord blood. The expression of insulin-like growth factor 2 is significant higher in normal glucose tolerance with macrosomia group (NGT-M compared to normal glucose tolerance with normal birthweight group (NGT-NBW group both in placenta and umbilical cord blood. A model with interaction term of gene expression of IGF2 and H19 found that IGF2 and the joint action of IGF2 and H19 in placenta showed significantly relationship with GDM/NGT and GDM-NBW/NGT-NBW. A borderline significant association was seen among IGF2 and H19 in cord blood and GDM-M/NGT-M. The methylation level at different CpG sites of insulin-like growth factor 2 and H19 in umbilical cord blood was also significantly different among groups. Based on the multivariable linear regression analysis, the methylation of the insulin-like growth factor 2 / H19 is closely related to birth weight and intrauterine hyperglycemia.We confirmed the existence of alteration in DNA methylation in umbilical cord blood exposed to intrauterine hyperglycemia and

  2. Enantiomeric ratios as an indicator of exposure processes for persistent pollutants in human placentas

    DEFF Research Database (Denmark)

    Shen, Heqing; Virtanen, H E; Main, Katharina M

    2006-01-01

    The enantiomeric ratios (ER) of alpha-HCH and o,p'-DDT ((+)-isomer concentration/(-)-isomer concentration) and o,p'-DDD (first eluting enantiomer/second enantiomer) were investigated in 112 human placentas from Finnish boys collected 1997-2001. Both o,p'-DDD and alpha-HCH showed changes in their ER...

  3. Effects of netrin-1 and netrin-1 knockdown on human umbilical vein endothelial cells and angiogenesis of rat placenta.

    Science.gov (United States)

    Xie, H; Zou, L; Zhu, J; Yang, Y

    2011-08-01

    Angiogenesis is an important process essential for the development of placenta. Netrin-1 was first discovered in nervous system and was later found to play roles in angiogenesis. In order to better understand the functional relevance of netrin-1 in placental angiogenesis, we investigated the effect of netrin-1 on human umbilical vein endothelial cells (HUVECs) and rat placenta by employing up-regulation and down-regulation strategies. HUVECs and rat placenta were treated with recombinant netrin-1, and netrin-1 expression in the cells and placenta was reduced by short hairpin RNA (shRNA) in vitro and in vivo. The inhibition efficiency was determined by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting. The expression of netrin-1 was immunohistochemically located. The results demonstrated that netrin-1 promoted viability, proliferation, migration and tube formation of HUVECs. A strong reduction in cell capability was observed in vitro after netrin-1 expression was inhibited with shRNA. Netrin-1 accelerated neovascularization of placenta in pregnant rats. Suppression of netrin-1 expression in placenta resulted in reduced vascular sprouting in vivo. These findings suggest that netrin-1 is essential for the proper functioning of HUVECs and angiogenesis of rat placenta, and it is involved in the development of placenta and fetus. The proangiogenic effect of netrin-1 might offer an alternative therapeutic approach for the treatment of vascular disease of placenta.

  4. Increased levels of cell-free human placental lactogen mRNA at 28-32 gestational weeks in plasma of pregnant women with placenta previa and invasive placenta.

    Science.gov (United States)

    Kawashima, Akihiro; Sekizawa, Akihiko; Ventura, Walter; Koide, Keiko; Hori, Kyouko; Okai, Takashi; Masashi, Yoshida; Furuya, Kenichi; Mizumoto, Yoshifumi

    2014-02-01

    We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive placenta (n = 5), and normal pregnancies (n = 92). Median (range) hPL mRNA was significantly higher in women with placenta previa, 782 (10-2301) copies/mL of plasma, and in those with invasive placenta, 615 (522-2102) copies/mL of plasma, when compared to normal pregnancies, 90 (4-4407) copies/mL of plasma, P placenta among women with placenta previa. In conclusion, expression of hPL mRNA is increased in plasma of women with placenta previa and invasive placenta at 28 to 32 weeks of gestation.

  5. Regenerative efficacy of mesenchymal stromal cells from human placenta in sensorineural hearing loss.

    Science.gov (United States)

    Kil, Kicheol; Choi, Mi Young; Kong, Ji Sun; Kim, Woo Jin; Park, Kyoung Ho

    2016-12-01

    Hearing loss is a common chronic disorder characterized by decline of auditory function. The global population have suffered from deafness and the transplantation of stem cells is regarded as a therapeutic strategy for this disease. We collected placenta from a total of 13 samples of full term pregnant women and isolated MSCs derived from human placenta and transplanted MSCs on deaf animal model. The normal group and the sensorineural hearing loss (SNHL) group and the experimental (transplanted MSCs) group were compared and estimated hearing level using auditory brainstem response (ABR) recordings and the otoacoustic emission (OAE) test. ABR threshold value and DPOAE level showed that MSCs transplantation groups was improved than the SNHL group. And the number of spiral ganglion neurons were increased in all turn of the cochlea. And there was no evidence of acute immunological rejection and inflammation response was not observed. This study is to evaluate regenerative efficacy of hearing loss by transplanting mesenchymal stromal cells (MSCs) derived from human placenta (amnion and chorion) in deaf animal model. We identified that MSCs transplantation restored auditory impairment and promoted cell regeneration. We hope to overcome sensorineural hearing loss by transplanting stem cells such as mesenchymal stromal cells (MSCs) from easily accessible adult stem cell source in placenta. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting.

    Directory of Open Access Journals (Sweden)

    Marta Sanchez-Delgado

    2016-11-01

    Full Text Available Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans. With the exception of a few known paternally methylated germline differentially methylated regions (DMRs associated with known imprinted domains, we demonstrate that sperm-derived methylation is reprogrammed by the blastocyst stage of development. In contrast a large number of oocyte-derived methylation differences survive to the blastocyst stage and uniquely persist as transiently methylated DMRs only in the placenta. Furthermore, we demonstrate that this phenomenon is exclusive to primates, since no placenta-specific maternal methylation was observed in mouse. Utilizing single cell RNA-seq datasets from human preimplantation embryos we show that following embryonic genome activation the maternally methylated transient DMRs can orchestrate imprinted expression. However despite showing widespread imprinted expression of genes in placenta, allele-specific transcriptional profiling revealed that not all placenta-specific DMRs coordinate imprinted expression and that this maternal methylation may be absent in a minority of samples, suggestive of polymorphic imprinted methylation.

  7. Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting

    Science.gov (United States)

    Court, Franck; Martin-Trujillo, Alex; Tayama, Chiharu; Kondova, Ivanela; Bontrop, Ronald; Poo-Llanillo, Maria Eugenia; Nakabayashi, Kazuhiko; Simón, Carlos; Monk, David

    2016-01-01

    Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans. With the exception of a few known paternally methylated germline differentially methylated regions (DMRs) associated with known imprinted domains, we demonstrate that sperm-derived methylation is reprogrammed by the blastocyst stage of development. In contrast a large number of oocyte-derived methylation differences survive to the blastocyst stage and uniquely persist as transiently methylated DMRs only in the placenta. Furthermore, we demonstrate that this phenomenon is exclusive to primates, since no placenta-specific maternal methylation was observed in mouse. Utilizing single cell RNA-seq datasets from human preimplantation embryos we show that following embryonic genome activation the maternally methylated transient DMRs can orchestrate imprinted expression. However despite showing widespread imprinted expression of genes in placenta, allele-specific transcriptional profiling revealed that not all placenta-specific DMRs coordinate imprinted expression and that this maternal methylation may be absent in a minority of samples, suggestive of polymorphic imprinted methylation. PMID:27835649

  8. Natural killer cells and HLA-G expression in the basal decidua of human placenta adhesiva.

    NARCIS (Netherlands)

    Beekhuizen, H.J. van; Joosten, I.; Lotgering, F.K.; Bulten, J.; Kempen, L.C.L.T. van

    2010-01-01

    Retained placenta is caused by abnormal adherence of the placenta to the uterine wall, leading to delayed expulsion of the placenta and causing postpartum haemorrhage. The mildest form of retained placenta is the placenta adhesiva (PA), of which the cause is unknown. The aim of our study was to expl

  9. In vitro and in vivo human herpesvirus 8 infection of placenta.

    Directory of Open Access Journals (Sweden)

    Mariantonietta Di Stefano

    Full Text Available Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8 infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women.

  10. Saline obtaining and time standardization of prothrombin using thromboplastin of human placenta.

    Directory of Open Access Journals (Sweden)

    María de Jesús Sánchez Bouza

    2003-07-01

    Full Text Available Background: Determining prothombine ‘s time is an important lab test in the study of coagulation disorders. To develop this essay the main reactive was thromboplastin , a substance that is presented in tissue and that has been obtained habitually from the human brain or certain animals but its extraction in labs or its commercial acquisition is difficult at present. Objective: To obtain Thromboplastin throughout the extraction of human placenta and to standardise the determination of pro-time into the obtained reactive Method: Placenta from normal delivery was used from which thromboplastin was obtained using a saline extraction. The reactive was compared with thromboplastin from human brain from ¨Dr. Hermanos Ameijeiras¨ Hospital in Havana City in a group of patients with and without anticoagulant treatment . With the extracted thromplastin similar or compatible results were obtained than with the habitual reactives by using easier and cheaper process.

  11. MOUSE ANTIBODY RESPONSE FOLLOWING REPETITIVE INJECTIONS OF GAMMA-IRRADIATED HUMAN PLACENTA COLLAGENA

    Institute of Scientific and Technical Information of China (English)

    刘秉慈; MelvinSpira; 许增禄

    1994-01-01

    Injectable bovine collagen has been used clinically for years.But both the necessity of repeated injections to maintain corrections and the question of adverse allergic reactions developing from the use of a xenogenic collagen have been an area of serious concern.To overoome these adyerse effects,we have developed injectable collagen preparations from human placenta.Gamma irradiation was used for sterilization and crosslinking of the collagen.We observed the mouse immune respose to gamma-irradiated human placenta soluble and insoluble collagen follow-ing multiple injections.After six injections of these materials,no total IgG level increase was found,nor was anti-body specifically directed against human collagen found.Mouse antibody levels were also observed following Zyderm Ⅱ and Zyplast repetitive injections and follow-ing repetitive implantations of coated vicryl and chromic gut.No humoral immune response was found in this het-erologous type system.

  12. Leptin and its Receptors in Human Placenta of Small, Adequate, and Large for Gestational Age Newborns.

    Science.gov (United States)

    Lazo-de-la-Vega-Monroy, Maria-Luisa; González-Domínguez, Martha I; Zaina, Silvio; Sabanero, Myrna; Daza-Benítez, Leonel; Malacara, Juan Manuel; Barbosa-Sabanero, Gloria

    2017-05-01

    Alterations in birth weight impact postnatal outcome and adult metabolic health. Therefore, fetal growth regulation is crucial for preventing chronic metabolic diseases. Leptin has been suggested to play an important role in placental and fetal growth, albeit its specific mechanisms of action have not been elucidated. The aim of this study was to analyze leptin concentrations in placenta, cord blood, and maternal blood of SGA, AGA, and LGA (small, adequate and large for gestational age, respectively) newborns, as well as placental leptin receptor (LEPRa and LEPRb) protein expression. We performed a cross-sectional comparative study in 3 groups of healthy mothers and their term newborns at delivery (SGA, AGA, and LGA, n=20 per group). Placental, maternal blood, and cord blood leptin content were measured by ELISA. Placental LEPRa and LEPRb protein expression were determined by Western Blot. Maternal leptin concentrations correlated positively with maternal weight before and at the end of gestation, without differences between groups. Cord leptin is higher in LGA and lower in SGA, whereas placental leptin is higher in SGA. Placental leptin was inversely correlated with placental weight, independently from maternal weight and gestational age. Both LEPRa and LEPRb expression are lower in SGA, while LEPRa positively correlated with placental weight and birthweight. The current findings indicate that placental leptin and its receptors are differentially expressed in SGA, AGA, and LGA newborns. We suggest that placental leptin and LEPR protein expression may influence placental growth and thus, birth weight. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Cord Blood

    Directory of Open Access Journals (Sweden)

    Saeed Abroun

    2014-05-01

    Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

  14. Adhering maternal platelets can contribute to the cytokine and chemokine cocktail released by human first trimester villous placenta.

    Science.gov (United States)

    Blaschitz, A; Siwetz, M; Schlenke, P; Gauster, M

    2015-11-01

    Placental villous explant culture has been increasingly recognized as suitable model to study secretion of inflammatory and immune modulating factors by human placenta. Most of these factors likely derive from the syncytiotrophoblast, whereas extraplacental sources such as maternal peripheral blood cells are rarely considered. Due to their small size and absence of a nucleus, platelets adhering to perivillous fibrinoid of normal placenta are frequently ignored in routine immunohistochemistry. Here we demonstrate adhering maternal platelets on first trimester placental villi after explant culture and point out that platelet-derived factors must be considered when analyzing the inflammatory secretion profile of human placenta.

  15. Human placenta expresses both peripheral and neuronal isoform of tryptophan hydroxylase.

    Science.gov (United States)

    Laurent, Laetitia; Deroy, Kathy; St-Pierre, Joey; Côté, Francine; Sanderson, J Thomas; Vaillancourt, Cathy

    2017-09-01

    The role of placental serotonin has been an active topic of research notably because of its crucial role in brain development. However, which cell types synthesize serotonin in human placenta remains unknown. Moreover, it is not known if the two tryptophan hydroxylase isoforms (TPH1 and TPH2), the rate-limiting enzymes in serotonin biosynthesis, are expressed in placenta. Human placentas were obtained in first trimester or at term, and trophoblast cells were isolated and purified using a magnetic cell sorter and placed in primary culture. The tissue sublocalization of each TPH was determined by immunohistochemistry. TPH expression in primary villous trophoblasts was determined by PCR and immunoblotting, and serotonin secretion by LC-MS/MS. Villous cytotrophoblasts, syncytiotrophoblast, fetal capillaries, extravillous cytotrophoblasts, and decidual cells co-expressed TPH1 and TPH2. Moreover, mRNA and protein levels of both TPHs were detected in human primary trophoblast as well as in mouse placental tissues. Finally, human trophoblast cells were shown to produce serotonin de novo. This study demonstrates that both TPH1 and TPH2 are expressed in human and mouse placenta throughout pregnancy and helps to better understand the placental serotonin system, which is crucial for healthy pregnancy and fetal development. It is therefore important to further understand regulation of the placental serotonin system and how its disruption during pregnancy may impact the developing fetus and subsequent child programming. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  16. Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour.

    Science.gov (United States)

    Alwarfaly, Samy; Abdulsid, Akrem; Hanretty, Kevin; Lyall, Fiona

    2014-01-01

    Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1-3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role.

  17. Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.

    Science.gov (United States)

    Shekhawat, Prem; Bennett, Michael J; Sadovsky, Yoel; Nelson, D Michael; Rakheja, Dinesh; Strauss, Arnold W

    2003-06-01

    The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.

  18. In vivo quantification of {sup 18}F-Fdg uptake in human placenta during early pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, P.; Jan, S.; Trebossen, R.; Maroy, R. [CEA, DSV, I2BM, SHFJ, F-91401 Orsay (France); Champion, C. [Univ Paul Verlaine Metz, Lab Phys Mol et Collis, Inst Phys, Metz (France); Hindie, E. [Hop St Antoine, AP-HP, F-75571 Paris (France); Hindie, E. [Univ Paris 07, IMDCT, IUH, Ecole Doctorale B2T, F-75221 Paris (France)

    2008-07-01

    {sup 18}F-FDG is the most widely used PET radiopharmaceutical. Nevertheless, no data for {sup 18}F-FDG uptake in the human placenta have been reported. We recently reported on embryo dosimetry in a woman who underwent an {sup 18}F-FDG PET/CT scan during early pregnancy. In the present work we attempt an in vivo quantification of the {sup 18}F-FDG uptake by the placenta. The 27-y-old woman received 320 MBq of {sup 18}F-FDG for a follow-up study for Hodgkin's lymphoma and was later discovered to be pregnant (embryo age 8 wk). Imaging started 1 h after injection. The maximum placental tissue uptake (SUVmax) was 2.5. This value was conservatively attributed to the entire placental volume, i.e., 45 mL, a value representative of the average dimensions of a normal placenta at 8 wk. On the basis of these measurements, placenta {sup 18}F-FDG uptake in our patient was 0.19% of the injected activity. A Monte Carlo simulation was used to derive the photon dose to the embryo from the placenta (0.022 * 10{sup -2} mGy per MBq of injected {sup 18}F-FDG) and from the surrounding amniotic fluid (0.017 * 10{sup -2} mGy MBq{sup -1}). This increases our previously calculated dose (3.3 * 10{sup -2} mGy MBq{sup -1}) by only a small fraction (1.18%), which does not justify modifying the previous estimate given the overall uncertainties. (authors)

  19. The development of a dynamic model for microvascular research and practice using human placenta: a preliminary report.

    Science.gov (United States)

    Waterhouse, N; Moss, A L; Townsend, P L

    1985-07-01

    Human placenta has been investigated in an attempt to develop a non-animal model for microvascular research and practice, with a dynamic artificial circulation. Initial work has been encouraging and further development is in progress.

  20. Expression and localization of the omega-3 fatty acid receptor GPR120 in human term placenta.

    Science.gov (United States)

    Lager, S; Ramirez, V I; Gaccioli, F; Jansson, T; Powell, T L

    2014-07-01

    Fatty acids can function as signaling molecules, acting through receptors in the cytosol or on the cell surface. G-Protein Receptor (GPR)120 is a membrane-bound receptor mediating anti-inflammatory and insulin-sensitizing effects of the omega-3 fatty acid docohexaenoic acid (DHA). GPR120 dysfunction is associated with obesity in humans. Cellular localization of GPR120 and the influence of maternal obesity on GPR120 protein expression in the placenta are unknown. Herein we demonstrate that GPR120 is predominantly expressed in the microvillous membrane (MVM) of human placenta and that the expression level of this receptor in MVM is not altered by maternal body mass index (BMI).

  1. Oxytocinase-immunohistochemical demonstration in the immature and term human placenta.

    Science.gov (United States)

    Small, C W; Watkins, W B

    1975-10-27

    Oxytocinase (cystine aminopeptidase) was purified from human retroplacental serum by a combination of fractional precipitation, hydroxylapatite chromatography and gel exlusion chromatography on Sephadex G-200. The purified enzyme possessed a specific activity of 980 mIU/mg using L-cystine-di-p-nitroanilide as substrate. This represented a 3200 fold concentration from the starting material in an overall yield of 12%. Antibodies against oxytocinase were raised in rabbits and the gamma-globulins fraction labelled with fluorescein isothiocyanate prior to its use in the immunofluorescence histochemical localization of the enzyme in human placental tissue. Oxytocinase was confined to the syncytiotrophoblastic cells of normal term, and immature placentas as well as in placentas from patients suffering from severe toxaemia. Specific immunofluorescence was also present in the outer margins of the chorion and to a lesser extent in the amnion.

  2. Human umbilical cord mesenchymal stem cells and the treatment of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    CAO Fu-jiang; FENG Shi-qing

    2009-01-01

    Objective To review the recent studies about human umbilical cord mesenchymal stem cells (hUCMSCs) and advances in the treatment of spinal cord injury, Data sources Published articles (1983-2007) about hUCMSCs and spinal cord injury were selected using Medline. Study selection Articles selected were relevant to development of mesenchymal stem cells (MSCs) for transplantation in spinal cord injury therapy. Of 258 originally identifiied arises 51 were selected that specifically addressed the stated purpose. Results Recent work has revealed that hUCMSCs share most of the characteristics with MSCs derived from bone marrow and are more appropriate to transplantation for cell based therapies. Conclusions Human umbilical cord could be regarded as a source of MSCs for experimental and clinical needs. In addition, as a peculiar source of stem cells, hUCMSCs may play an important role in the treatment of spinal cord injury.

  3. Effect of human neural progenitor cells on injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    XU Guang-hui; BAI Jin-zhu; CAI Qin-lin; LI Xiao-xia; LI Ling-song; SHEN Li

    2005-01-01

    Objective: To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats.Methods: Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan (BBB) locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry.Results: Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats.Conclusions: Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.

  4. Increased Levels of Cell-Free Human Placental Lactogen mRNA at 28-32 Gestational Weeks in Plasma of Pregnant Women With Placenta Previa and Invasive Placenta

    OpenAIRE

    2014-01-01

    We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive place...

  5. Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta

    DEFF Research Database (Denmark)

    Storm, Tina; Christensen, Erik I; Christensen, Julie Nelly

    2016-01-01

    The membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital...... nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly...... clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal...

  6. Placenta abruptio

    Science.gov (United States)

    ... Philadelphia, PA: Elsevier; 2017:chap 18. Hull AD, Resnik R. Placenta previa, placenta accreta, abruptio placentae, and vasa previa. In: Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR, Greene ...

  7. Total reflection X-ray fluorescence as a fast multielemental technique for human placenta sample analysis

    Science.gov (United States)

    Marguí, E.; Ricketts, P.; Fletcher, H.; Karydas, A. G.; Migliori, A.; Leani, J. J.; Hidalgo, M.; Queralt, I.; Voutchkov, M.

    2017-04-01

    In the present contribution, benchtop total reflection X-ray fluorescence spectrometry (TXRF) has been evaluated as a cost-effective multielemental analytical technique for human placenta analysis. An easy and rapid sample preparation consisting of suspending 50 mg of sample in 1 mL of a Triton 1% solution in deionized water showed to be the most suitable for this kind of samples. However, for comparison purposes, an acidic microwave acidic digestion procedure was also applied. For both sample treatment methodologies, limits of detection for most elements were in the low mg/kg level. Accurate and precise results were obtained using internal standardization as quantification approach and applying a correction factor to compensate for absorption effects. The correction factor was based on the proportional ratio between the slurry preparation results and those obtained for the analysis of a set of human placenta samples analysed by microwave acidic digestion and ICP-AES analysis. As a study case, the developed TXRF methodology was applied for multielemental analysis (K, Ca, Fe, Cu, Zn, As, Se, Br, Rb and Sr) of several healthy women's placenta samples from two regions in Jamaica.

  8. Expression of Adiponectin Receptors in Human Placenta and Its Possible Implication in Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Naglaa F. Al Husseini

    2010-01-01

    Full Text Available Problem statement: Similar to obese patients and type 2 diabetic patients, adiponectin levels are reduced in former Gestational Diabetes Mellitus (GDM patients and are lower in GDM women during late pregnancy compared with pregnant control subjects matched for BMI. Diabetic insult at later stages in gestation, such as may occur in gestational diabetes, will foremost lead to short-term changes in a variety of molecules for key functions including gene expression in the placenta. Approach: In this study we assessed the expression of adiponectin receptors in human placenta to identify the site (s of expression and to clarify the effect of gestational diabetes in this expression. This study was carried on 10 normoglycemic pregnant women and 20 GDM women. The placental tissue was collected immediately after delivery and tissue biopsies were taken from both fetal and maternal sides of each placenta. One step-RT-PCR for ADIPOR1 and ADIPOR2 was done by Real Time PCR using Syber Green technique. Relative quantification of mRNA of the ADIPOR1 and ADIPOR2 genes was measured using ABI7900 Real Time machine. Results: Both types of Adiponectin Receptors (ADIPOR1 and ADIPOR2 are expressed in human placenta. ADIPOR1 is more highly expressed than ADIPOR2 in both fetal and maternal sides of GDM cases and normal pregnant women. ADIPOR1 mRNA expression was significantly up regulated in GDM women compared to normal pregnant women, whereas no significant difference in the expression of ADIPOR2 was detected between the two groups. There was no evidence of maternal-fetal side difference in the expression of adiponectin receptors in GDM cases but in normal pregnant women there is a statistically significant difference between both sides in the expression of both ADIPOR1 and ADIPOR2. Conclusion: We concluded that adiponectin plays an important role in mediation the glucose metabolism in fetal tissues through its receptors, mainly Adiponectin Receptor 1 (ADIPOR1.

  9. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... of lipid transfer from the mother to the developing fetus....

  10. Progesterone receptor B promoter hypermethylation in human placenta after labor onset.

    Science.gov (United States)

    Zhuang, Yanyan; Cui, Hong; Liu, Sishi; Zheng, Dongming; Liu, Caixia

    2015-03-01

    To determine the methylation status of progesterone receptor B (PR-B) promoter and how PR-B regulates progesterone action in placenta during human pregnancy. Placentas were obtained from the pregnancy women at term who underwent cesarean delivery and vaginal delivery. The methylation status of the PR-B promoter was analyzed using the methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing PCR. And the messenger RNA (mRNA) and protein expression of the PR-B and DNA methyltransferases (DNMTs) were determined by quantitative real-time PCR and Western blot. Compared with the cesarean group, the placentas of vaginal delivery group had greater levels of PR-B DNA methylation, and the PR-B, DNMT1, DNMT3a, and DNMT3b mRNA and protein expression were significantly decreased. Progesterone receptor B methylation occurs with high frequency after labor onset and may play an important epigenetic mechanism of labor-related PR-B negative expression, thereby mediating the biological process of functional progesterone withdrawal at term for parturition. © The Author(s) 2014.

  11. Transfer in vitro of three benzodiazepines across the human placenta.

    Science.gov (United States)

    Guerre-Millo, M; Rey, E; Challier, J C; Turquais, J M; d'Athis, P; Olive, G

    1979-04-17

    A comparative study of the placental transfer to the foetus of three benzodiazepines was performed using a dual perfusion system of the human placental lobule. A transport fraction was calculated for each benzodiazepine and was compared with reference substances. Relative to antipyrine, the transport fraction of diazepam was 85%, and that of nordiazepam was 84%. The transport fraction of clorazepate represented only 20% of that of tritiated water. The relatively high transfer of diazepam and nordiazepam can be attributed to their high lipid solubility, and the lower transfer of clorazepate is due to its polar nature. It is suggested that in certain instances this benzodiazepine may be of especial value to obstetricians.

  12. Micro- and Nano-vesicles from First Trimester Human Placentae Carry Flt-1 and Levels Are Increased in Severe Preeclampsia.

    Science.gov (United States)

    Tong, Mancy; Chen, Qi; James, Joanna L; Stone, Peter R; Chamley, Lawrence W

    2017-01-01

    Preeclampsia is a life-threatening hypertensive disease affecting 3-5% of pregnancies. While the pathogenesis of preeclampsia remains unclear, it is known that placenta-derived factors trigger the disease by activating maternal endothelial cells prior to the onset of clinical symptoms. Extracellular vesicles (EVs) of different sizes extruded by the placenta may be one factor. The truncated/secreted form of Flt-1 (sFlt-1) has also been implicated in the pathogenesis of preeclampsia. We investigated whether placental EV production is altered in preeclampsia such that they induce endothelial cell activation, and whether (s)Flt-1 is involved. Macro-, micro-, and nano-vesicles were collected from normal and preeclamptic (PE) placental explants, and separated by differential centrifugation. The number and size of micro- and nano-vesicles was measured by nanoparticle tracking analysis and their ability to activate endothelial cells was quantified by endothelial cell intercellular adhesion molecule 1 expression and monocyte adhesion. The levels of Flt-1 were measured by western blots and ELISA. PE placentae extruded significantly more micro- and nano-vesicles than control placentae and the extruded micro-vesicles were larger than those from control placentae. Micro- and nano-vesicles from both first trimester and term human placentae carried Flt-1 and levels were significantly increased in EVs from severe, but not mild, PE compared to normotensive placentae. All fractions of EVs from PE placentae activated endothelial cells, and for micro- and nano-vesicles, activation was reduced in the presence of exogenous vascular endothelial growth factor (VEGF), a Flt-1 neutralizing antibody, or by pre-treatment with VEGF. While EV-bound VEGF constituted over 20% of the total detected VEGF secreted by PE and normotensive placentae, EV-bound Flt-1 did not significantly contribute to the total level of sFlt-1/Flt-1 released by human third trimester placentae. Micro- and nano

  13. The effects of pravastatin on the normal human placenta: Lessons from ex-vivo models

    Science.gov (United States)

    Swissa, Shani S.; Feinshtein, Valeria; Huleihel, Mahmoud; Holcberg, Gershon; Dukler, Doron

    2017-01-01

    Introduction Research in animal models and preliminary clinical studies in humans support the use of pravastatin for the prevention of preeclampsia. However, its use during pregnancy is still controversial due to limited data about its effect on the human placenta and fetus. Methods In the present study, human placental cotyledons were perfused in the absence or presence of pravastatin in the maternal reservoir (PraM). In addition, placental explants were treated with pravastatin for 5, 24 and 72 h under normoxia and hypoxia. We monitored the secretion of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), endothelial nitric oxide synthase (eNOS) expression and activation and the fetal vasoconstriction response to angiotensin-II. Results The concentrations of PlGF, sFlt-1 and sEng were not significantly altered by pravastatin in PraM cotyledons and in placental explants compared to control. Under hypoxic conditions, pravastatin decreased sFlt-1 concentrations. eNOS expression was significantly increased in PraM cotyledons but not in pravastatin-treated placental explants cultured under normoxia or hypoxia. eNOS phosphorylation was not significantly affected by pravastatin. The feto-placental vascular tone and the fetal vasoconstriction response to angiotensin-II, did not change following exposure of the maternal circulation to pravastatin. Conclusion We found that pravastatin does not alter the essential physiological functions of the placenta investigated in the study. The relevance of the study lays in the fact that it expands the current knowledge obtained thus far regarding the effect of the drug on the normal human placenta. This data is reassuring and important for clinicians that consider the treatment of high-risk patients with pravastatin, a treatment that exposes some normal pregnancies to the drug. PMID:28199380

  14. Probable preventive effects of placenta from oxidative stress; Evaluation of total antioxidant status, total oxidant status and oxidative stress index in fetal cord blood during the delivery.

    Science.gov (United States)

    Camkurt, Mehmet Akif; Fındıklı, Ebru; Tolun, Fatma İnanç; Bakacak, Murat; Bal, Nilay Gül; Sakallı, Hilal; Güneş, Mehmet

    2016-06-30

    Depression in pregnancy may have negative effects on birth outcomes. It may also effect the intrauterine environment of the fetus. The umbilical cord is the conduit between the fetus and placenta, and functions in the transport between fetus and mother. Investigating biochemical parameters in fetal cord blood (FCB) during delivery may be helpful to understanding to what the fetus is exposed to, at least in the last trimester. In this study, we aimed to investigate total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in the FCB of depressed mothers and healthy controls during delivery. Our study included 33 depressed mothers and 37 healthy controls. TAS, TOS, and OSI were measured according to Erel's method. We found that TAS, TOS, and OSI levels were similar in patients and healthy controls; however, the birth weights of depressed patients were significantly lower than those of healthy controls. Our results suggest that the placental barrier may prevent from oxidative stress. Future studies should include blood samples collected simultaneously from mothers during delivery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Susceptibility of human placenta derived mesenchymal stromal/stem cells to human herpesviruses infection.

    Directory of Open Access Journals (Sweden)

    Simone Avanzi

    Full Text Available Fetal membranes (FM derived mesenchymal stromal/stem cells (MSCs are higher in number, expansion and differentiation abilities compared with those obtained from adult tissues, including bone marrow. Upon systemic administration, ex vivo expanded FM-MSCs preferentially home to damaged tissues promoting regenerative processes through their unique biological properties. These characteristics together with their immune-privileged nature and immune suppressive activity, a low infection rate and young age of placenta compared to other sources of SCs make FM-MSCs an attractive target for cell-based therapy and a valuable tool in regenerative medicine, currently being evaluated in clinical trials. In the present study we investigated the permissivity of FM-MSCs to all members of the human Herpesviridae family, an issue which is relevant to their purification, propagation, conservation and therapeutic use, as well as to their potential role in the vertical transmission of viral agents to the fetus and to their potential viral vector-mediated genetic modification. We present here evidence that FM-MSCs are fully permissive to infection with Herpes simplex virus 1 and 2 (HSV-1 and HSV-2, Varicella zoster virus (VZV, and Human Cytomegalovirus (HCMV, but not with Epstein-Barr virus (EBV, Human Herpesvirus-6, 7 and 8 (HHV-6, 7, 8 although these viruses are capable of entering FM-MSCs and transient, limited viral gene expression occurs. Our findings therefore strongly suggest that FM-MSCs should be screened for the presence of herpesviruses before xenotransplantation. In addition, they suggest that herpesviruses may be indicated as viral vectors for gene expression in MSCs both in gene therapy applications and in the selective induction of differentiation.

  16. Diagnostic insonation of extra uteri human placentas: no effect of lymphocytic sister chromatid exchange

    Energy Technology Data Exchange (ETDEWEB)

    Brulfert, A.; Ciaravino, V.; Miller, M.W.; Maulik, D.; Carstensen, E.L.

    1984-01-01

    Freshly delivered human placentas were exposed to ultrasound for 30 min using a diagnostic linear array unit. Blood was then drawn and cultured in the presence of bromodeoxyuridine, and the frequencies of sister chromatid exchanges (SCE) in the lymphocytes determined. There was no statistically significant difference in SCE frequencies between control and exposed cells; the frequencies of SCEs per cell ranged from 4.50 to 6.02 for control and from 4.66 to 6.10 for exposed cells in five separate experiments. Positive control mitomycin C treated cells were significantly affected, with more than 50 SCEs per cell. 20 references, 1 table.

  17. Construction of tissue-engineered cartilage using human placenta-derived stem cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the cartilage formation was observed by implantation into nude mice.Results showed that hPDSCs featured mesenchymal stem cells and maintained proliferation in vitro for over 30 passages while remaining undifferentiated.All results indicated that hPDSCs have the potential to differentiate into functional cartilage cells in vitro when combined with collagen sponge,which provided experimental evidence for prospective clinical application.

  18. Phospholipid scramblase 1 (PLSCR1) in villous trophoblast of the human placenta.

    Science.gov (United States)

    Berghold, Veronika M; Gauster, Martin; Hemmings, Denise G; Moser, Gerit; Kremshofer, Julia; Siwetz, Monika; Sundl, Monika; Huppertz, Berthold

    2015-04-01

    A crucial factor for effective villous trophoblast fusion in the human placenta is the transient deregulation of plasma membrane phospholipid asymmetry leading to externalization of phosphatidylserine to the outer membrane leaflet. Screening of scramblase family members implicated in the collapse of phospholipid asymmetry revealed that phospholipid scramblase 1 (PLSCR1) is strongly expressed in villous trophoblast. Therefore, we assessed the putative role of PLSCR1 in villous trophoblast fusion. Spatio-temporal analysis in first trimester and term placenta showed abundant expression of PLSCR1 in syncytiotrophoblast, macrophages and endothelial cells, while it was virtually absent in villous cytotrophoblasts. For functional studies, BeWo cells, isolated primary term trophoblasts and first trimester villous explants were used. During forskolin-mediated BeWo cell differentiation, neither PLSCR1 mRNA nor protein levels showed significant changes. In contrast, when primary trophoblasts were stimulated with Br-cAMP, a decrease in PLSCR1 mRNA and protein expression was observed. To elucidate a role for PLSCR1 in syncytialization, we used RNA interference and a chemical scramblase inhibitor, R5421 (ethanedioic acid). Silencing of PLSCR1 using siRNA had no effects while inhibition of scramblase activity by R5421 increased GCM-1 mRNA expression, beta-hCG protein secretion and fusion rates of BeWo cells. In primary trophoblasts and villous explants, no effects of siRNA or R5421 treatment on fusion were detected. This study provides data on PLSCR1 localization and general expression in the human placenta. The data make it tempting to speculate on a role of PLSCR1 in negatively regulating trophoblast fusion.

  19. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

    Science.gov (United States)

    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  20. Segmentation of the human spinal cord.

    Science.gov (United States)

    De Leener, Benjamin; Taso, Manuel; Cohen-Adad, Julien; Callot, Virginie

    2016-04-01

    Segmenting the spinal cord contour is a necessary step for quantifying spinal cord atrophy in various diseases. Delineating gray matter (GM) and white matter (WM) is also useful for quantifying GM atrophy or for extracting multiparametric MRI metrics into specific WM tracts. Spinal cord segmentation in clinical research is not as developed as brain segmentation, however with the substantial improvement of MR sequences adapted to spinal cord MR investigations, the field of spinal cord MR segmentation has advanced greatly within the last decade. Segmentation techniques with variable accuracy and degree of complexity have been developed and reported in the literature. In this paper, we review some of the existing methods for cord and WM/GM segmentation, including intensity-based, surface-based, and image-based methods. We also provide recommendations for validating spinal cord segmentation techniques, as it is important to understand the intrinsic characteristics of the methods and to evaluate their performance and limitations. Lastly, we illustrate some applications in the healthy and pathological spinal cord. One conclusion of this review is that robust and automatic segmentation is clinically relevant, as it would allow for longitudinal and group studies free from user bias as well as reproducible multicentric studies in large populations, thereby helping to further our understanding of the spinal cord pathophysiology and to develop new criteria for early detection of subclinical evolution for prognosis prediction and for patient management. Another conclusion is that at the present time, no single method adequately segments the cord and its substructure in all the cases encountered (abnormal intensities, loss of contrast, deformation of the cord, etc.). A combination of different approaches is thus advised for future developments, along with the introduction of probabilistic shape models. Maturation of standardized frameworks, multiplatform availability, inclusion

  1. Motoneuron differentiation of immortalized human spinal cord cell lines.

    Science.gov (United States)

    Li, R; Thode, S; Zhou, J; Richard, N; Pardinas, J; Rao, M S; Sah, D W

    2000-02-01

    Human motoneuron cell lines will be valuable tools for spinal cord research and drug discovery. To create such cell lines, we immortalized NCAM(+)/neurofilament(+) precursors from human embryonic spinal cord with a tetracycline repressible v-myc oncogene. Clonal NCAM(+)/neurofilament(+) cell lines differentiated exclusively into neurons within 1 week. These neurons displayed extensive processes, exhibited immunoreactivity for mature neuron-specific markers such as tau and synaptophysin, and fired action potentials upon current injection. Moreover, a clonal precursor cell line gave rise to multiple types of spinal cord neurons, including ChAT(+)/Lhx3(+)/Lhx4(+) motoneurons and GABA(+) interneurons. These neuronal restricted precursor cell lines will expedite the elucidation of molecular mechanisms that regulate the differentiation, maturation and survival of specific subsets of spinal cord neurons, and the identification and validation of novel drug targets for motoneuron diseases and spinal cord injury.

  2. Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta.

    Science.gov (United States)

    Dubé, Evemie; Gravel, Ariane; Martin, Coralie; Desparois, Guillaume; Moussa, Issa; Ethier-Chiasson, Maude; Forest, Jean-Claude; Giguère, Yves; Masse, André; Lafond, Julie

    2012-07-01

    Knowledge of the consequences of maternal obesity in human placental fatty acids (FA) transport and metabolism is limited. Animal studies suggest that placental uptake of maternal FA is altered by maternal overnutrition. We hypothesized that high maternal body mass index (BMI) affects human placental FA transport by modifying expression of key transporters. Full-term placentas were obtained by vaginal delivery from normal weight (BMI, 18.5-24.9 kg/m(2)) and obese (BMI > 30 kg/m(2)) women. Blood samples were collected from the mother at each trimester and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Lipoprotein lipase (LPL) activity was evaluated using enzyme fluorescence. In vitro linoleic acid transport was studied with isolated trophoblasts. Our results demonstrated that maternal obesity is associated with increased placental weight, decreased gestational age, decreased maternal high-density lipoprotein (HDL) levels during the first and third trimesters, increased maternal triglyceride levels during the second and third trimesters, and increased maternal T3 levels during all trimesters, and decreased maternal cholesterol (CHOL) and low-density lipoprotein (LDL) levels during the third trimester; and increased newborn CHOL, LDL, apolipoprotein B100, and T3 levels. Increases in placental CD36 mRNA and protein expression levels, decreased SLC27A4 and FABP1 mRNA and protein and FABP3 protein expression, and increased LPL activity and decreased villus cytotrophoblast linoleic acid transport were also observed. No changes were seen in expression of PPARA, PPARD, or PPARG mRNA and protein. Overall this study demonstrated that maternal obesity impacts placental FA uptake without affecting fetal growth. These changes, however, could modify the fetus metabolism and its predisposition to develop diseases later in life.

  3. Identification of Goodpasture target antigens in basement membranes of human glomeruli, lung, and placenta.

    Science.gov (United States)

    Weber, M; Köhler, H; Manns, M; Baum, H P; Meyer zum Büschenfelde, K H

    1987-01-01

    Collagenase-digests of human glomerular (GBM), alveolar (ABM), and placenta basement membranes (PBM) were separated by gel filtration columns and the pools rich in Goodpasture antigens (GP) were identified by an antibody inhibition-ELISA. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting on nitrocellulose membranes was performed with each basement membrane preparation. Sera from patients with florid GP-syndrome and antibodies to glomerular basement membrane (anti-GBM antibodies) were incubated with nitrocellulose strips of GBM, ABM, and PBM. Immunoperoxidase staining revealed reactivity with target antigens of 24, 26, 44, and 50 kD in the GBM and of 44 and 50 kD in the ABM and PBM, respectively. No corresponding reactivity was observed using convalescent GP-sera, sera from patients with other immunological diseases or sera from healthy blood donors. The antigens were sensitive to reduction. We conclude, that antigens of similar molecular-weights can be identified by anti-GBM positive sera in human glomerular, alveolar and placenta basement membranes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3608225

  4. /sup 125/I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

    1988-01-01

    Specific binding of /sup 125/I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class AB diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more /sup 125/I-hEGF than did fetal membranes (P<0.0001). There was no significant differnce in /sup 125/I-hEGF binding to fetal membranes from the various pregnancy states (P<0.05). /sup 125/I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P<0.05). The binding to placentas from pregnancies complicated by White class AB diabetes or large for gestational age infants, on the other hand, was not significantly different from that to placentas from normal and appropriate for gestational age pregnancies. /sup 125/I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P<0.05). Placental and fetal membrane /sup 125/I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P<0.05). Placental but not fetal membrane /sup 125/I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone.

  5. Ultrasound, color - normal umbilical cord (image)

    Science.gov (United States)

    ... is a normal color Doppler ultrasound of the umbilical cord performed at 30 weeks gestation. The cord is ... the cord, two arteries and one vein. The umbilical cord is connected to the placenta, located in the ...

  6. Natural killer cells and HLA-G expression in the basal decidua of human placenta adhesiva.

    Science.gov (United States)

    van Beekhuizen, H J; Joosten, I; Lotgering, F K; Bulten, J; van Kempen, L C

    2010-12-01

    Retained placenta is caused by abnormal adherence of the placenta to the uterine wall, leading to delayed expulsion of the placenta and causing postpartum haemorrhage. The mildest form of retained placenta is the placenta adhesiva (PA), of which the cause is unknown. The aim of our study was to explore possible differences in immune response in the basal decidua between PA and control placentas (CP). We performed a descriptive analysis of immunohistochemical differences in 17 PA and 10 CP. Our results show that in PA the amount of uterine natural killer (uNK) cells is significantly reduced (0.2 uNK cell/standardised area) as compared to CP (9.8 uNK cell/standardised area, p placenta.

  7. Human cytomegalovirus-induces cytokine changes in the placenta with implications for adverse pregnancy outcomes.

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    Stuart T Hamilton

    Full Text Available Human cytomegalovirus (CMV infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2 and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007, which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71 (n = 7 per group. Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001 (n = 25 per group. Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml, caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017. Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury.

  8. Elevated soluble CD163 in gestational diabetes mellitus: secretion from human placenta and adipose tissue.

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    Muhammad Furqan Bari

    Full Text Available Recently soluble CD163 (sCD163, a cleaved form of the macrophage receptor CD163, was identified as a macrophage-specific risk-predictor for developing Type 2 Diabetes. Here, we investigate circulating levels of sCD163 in gestational diabetes mellitus (GDM. Furthermore, given the role of the placenta in the pathogenesis of GDM, we assessed placental contribution to sCD163 secretion. Paired maternal (venous and umbilical vein blood samples from GDM (n = 18 and Body Mass Index (BMI matched control women (n = 20 delivered by caesarean section at 39-40 week gestation were assessed for circulating levels of sCD163, Tumour necrosis factor alpha (TNF-α and Interleukin 6 (IL-6. Media from explant culture of maternal subcutaneous fat and corresponding placental tissues were assayed for these same molecules. CD163 positive cell numbers were determined in placental and adipose tissues of GDM and control women. We found significantly elevated circulating sCD163 levels in GDM mothers (688.4±46.9 ng/ml vs. 505.6±38.6 ng/ml and their offspring (418.2±26.6 ng/ml vs. 336.3±24.4 ng/ml [p<0.05 for both] as compared to controls, together with elevated circulating TNF-α and IL-6 levels. Moreover, both GDM placentae (268.1±10.8 ng/ml/mg vs. 187.6±20.6 ng/ml/mg and adipose explants (41.1±2.7 ng/ml/mg vs. 26.6±2.4 ng/ml/mg released significantly more sCD163 than controls. Lastly, significantly more CD163 positive cells were observed in GDM placentae (25.7±1.1 vs. 22.1±1.2 and adipose tissue (19.1±1.1 vs 12.7±0.9 compared to controls. We describe elevated sCD163 levels in GDM and identify human placenta as a novel source of sCD163 suggesting that placental tissues might contribute to the increased levels of circulating sCD163 in GDM pregnancies.

  9. Corticotropin releasing hormone- and adreno-corticotropin-like immunoreactivity in human placenta, peripheral and uterine vein plasma.

    Science.gov (United States)

    Schulte, H M; Healy, D L

    1987-01-01

    The presence of corticotropin releasing hormone (CRH)-like immunoreactivity (IR) in human placenta and maternal peripheral blood has been reported by many investigators. However, its physiological role has not yet been defined. We investigated plasma and placental tissue from women at different times of pregnancy and performed peripheral and uterine vein sampling during caesarean section before and after removal of the placenta. Beside IR-CRH, IR-GRF and -GnRH as well as -ACTH and cortisol were measured. The highest content of CRH was found in placental extracts from end term (40 weeks) pregnancies and lower levels at an earlier stage (10 weeks). Plasma CRH from peripheral blood could be detected in some samples and was higher as pregnancy advanced. Thirty minutes after removal of the placenta CRH levels dropped in peripheral plasma and could not be detected in uterine vein samples. IR-ACTH plasma levels were within the range of normals, cortisol was elevated. Gel- and HPLC-chromatographie revealed that placental extracts coeluted with synthetic human CRH. The material from endterm placenta showed full bioactivity in the rat pituitary bio-assay. IR-GRF could only be detected in 10 weeks placental tissue and no IR-GnRH was measured. We conclude that CRH from the placenta is biologically active, however, cannot stimulate the maternal pituitary-adrenal-axis.

  10. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

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    Yajing Huang

    2016-01-01

    Full Text Available Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

  11. Mercury concentration in maternal serum, cord blood, and placenta in patients with amalgam dental fillings: effects on fetal biometric measurements.

    Science.gov (United States)

    Bedir Findik, Rahime; Celik, Huseyin Tugrul; Ersoy, Ali Ozgur; Tasci, Yasemin; Moraloglu, Ozlem; Karakaya, Jale

    2016-11-01

    We aimed to determine the extent to which mercury is transmitted from the mother to fetus via the umbilical cord in patients with amalgam dental fillings, and its effect on fetal biometric measurements. Twenty-eight patients as the study group with amalgam fillings, and 32 of them as the control group were included in this prospective case-control study. The mercury levels were measured in the maternal and cord venous sera, and the placental samples. Two groups were compared in terms of these and the fetal/neonatal biometric measurements. In the study group, the maternal and umbilical cord mercury levels were found to be significantly higher than those from the control group (p = 0.006 and p = 0.010, respectively). These high levels did not affect the fetal biometric measurements. The presence of high serum mercury levels in pregnant women with amalgam fillings is important, and warrants further long-term studies in order to investigate the fetal neurological effects as well.

  12. Analysis of Genomic DNA Methylation Levels in Human Placenta using Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry

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    Sulistyo Emantoko Dwi Putra

    2014-03-01

    Full Text Available Background: DNA-methylation is a common epigenetic tool which plays a crucial role in gene regulation and is essential for cell differentiation and embryonic development. The placenta is an important organ where gene activity can be regulated by epigenetic DNA modifications, including DNA methylation. This is of interest as, the placenta is the interface between the fetus and its environment, the mother. Exposure to environmental toxins and nutrition during pregnancy may alter DNA methylation of the placenta and subsequently placental function and as a result the phenotype of the offspring. The aim of this study was to develop a reliable method to quantify DNA methylation in large clinical studies. This will be a tool to analyze the degree of DNA methylation in the human placenta in relationship to clinical readouts. Methods: Liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MS technique was used for the quantification of the 5dmC/dG ratio in placentas from 248 healthy pregnancies. We were able to demonstrate that this method is a reliable and stable way to determine global placental DNA methylation in large clinical trials. Results/Conclusion: The degree of placental DNA methylation seen in our pilot study varies substantially from 2% to 5%. The clinical implications of this variation need to be demonstrated in adequately powered large studies.

  13. TNF-α alters the inflammatory secretion profile of human first trimester placenta.

    Science.gov (United States)

    Siwetz, Monika; Blaschitz, Astrid; El-Heliebi, Amin; Hiden, Ursula; Desoye, Gernot; Huppertz, Berthold; Gauster, Martin

    2016-04-01

    Implantation and subsequent placental development depend on a well-orchestrated interaction between fetal and maternal tissues, involving a fine balanced synergistic cross-talk of inflammatory and immune-modulating factors. Tumor necrosis factor (TNF)-α has been increasingly recognized as pivotal factor for successful pregnancy, although high maternal TNF-α levels are associated with a number of adverse pregnancy conditions including gestational hypertension and gestational diabetes mellitus. This study describes effects of exogenously applied TNF-α, mimicking increased maternal TNF-α levels, on the secretion profile of inflammation associated factors in human first trimester villous placenta. Conditioned culture media from first trimester villous placental explants were analyzed by inflammation antibody arrays and ELISA after 48 h culture in the presence or absence of TNF-α. Inflammation antibody arrays identified interleukin (IL)-6, IL-8, chemokine (C-C motif) ligand 2 (CCL2), CCL4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most abundantly secreted inflammation-associated factors under basal culture conditions. In the presence of TNF-α, secretion of GM-CSF, CCL5, and IL-10 increased, whereas IL-4 and macrophage CSF levels decreased compared with controls. ELISA analysis verified antibody arrays by showing significantly increased synthesis and release of GM-CSF and CCL5 by placental explants in response to TNF-α. Immunohistochemistry localized GM-CSF in the villous trophoblast compartment, whereas CCL5 was detected in maternal platelets adhering to perivillous fibrin deposits on the villous surface. mRNA-based in situ padlock probe approach localized GM-CSF and CCL5 transcripts in the villous trophoblast layer and the villous stroma. Results from this study suggest that the inflammatory secretion profile of human first trimester placenta shifts towards increased levels of GM-CSF, CCL5, and IL10 in response to elevated maternal

  14. Fractionation of cystine aminopeptidases ('oxytocinase') from term human placenta and maternal serum.

    Science.gov (United States)

    Gopalaswamy, G; Balasubramaniam, N; Kanagasabapathy, A S

    1984-12-15

    Cystine aminopeptidase (EC 3.4.11.3) enzymes, present in term human placenta and maternal serum, were compared with respect to their behaviour on ion-exchange columns, Km and pH optima, chelator, metal ion and L-methionine effects, Sepharose 6B elution profiles and molecular weights. From placental extracts two activity peaks (CAS I and II) hydrolysing S-benzyl L-cysteine paranitroanilide were separated on DEAE Sephacel. Differences in properties between the two forms were evident. Maternal serum enzyme eluted from the DEAE Sephacel column in a position similar to that of placental CAS I. In addition, the maternal serum enzyme was similar in properties to placental CAS I. It is possible that of all the different cystyl aminopeptidase enzyme systems present in placental tissue, only one appears in maternal blood.

  15. Antioxidants activities and concentration of selenium, zinc and copper in preterm and IUGR human placentas.

    Science.gov (United States)

    Zadrozna, Monika; Gawlik, Małgorzata; Nowak, Barbara; Marcinek, Antoni; Mrowiec, Halina; Walas, Stanisław; Wietecha-Posłuszny, Renata; Zagrodzki, Paweł

    2009-01-01

    The aim of this study was to examine changes in activities of cytochrome c oxidase (CCO), glucose-6-phosphate dehydrogenase (G6PDH), Cu-Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), glutathione (GSH) levels and copper (Cu), zinc (Zn) and selenium (Se) concentrations, and to assess the possible differences between preterm placentas, placentas from term pregnancies complicated by intrauterine growth restriction (IUGR) and full-term control placentas. The enzyme activities and the level of GSH decreased in IUGR and preterm placentas in comparison with the control group. CCO activity and GSH level in preterm placentas were markedly lower compared with the IUGR (P<0.01; P<0.05) and control (P<0.01; P<0.05) placentas, respectively. In IUGR placentas the level of Cu was reduced by 23% (P<0.05) and Zn by 37%. In preterm placentas the level of Cu was reduced by 19% and Zn by 42%. Se level in IUGR and preterm placentas was higher (P<0.05) by 28% and 32% than in control group, respectively. The strong relation was observed between birth weight and CCO activity, birth weight and Cu-Zn SOD activity, and a low level of Zn and Cu influenced the birth weight especially in IUGR cases. Moreover, the strong inverse correlation between Se level and birth weight, Se level and placental weight and Se level and CCO activity are new findings.

  16. Myelin water fraction in human cervical spinal cord in vivo.

    Science.gov (United States)

    Wu, Yijing; Alexander, Andrew L; Fleming, John O; Duncan, Ian D; Field, Aaron S

    2006-01-01

    The noninvasive discrimination of myelin disease from axonal loss and other pathologic confounds remains an unsolved problem in multiple sclerosis but may be possible through magnetic resonance quantitation of the intramyelinic water compartment. Technical challenges have limited the study of this approach in the spinal cord, a common site of involvement in multiple sclerosis. This technical note reports the test-retest reproducibility of a short T2-based estimate of myelin content in human spinal cord in vivo.

  17. Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model

    Science.gov (United States)

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F.; Wick, Peter; von Mandach, Ursula

    2013-01-01

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1. Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3, can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. PMID:23851364

  18. Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model.

    Science.gov (United States)

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F; Wick, Peter; von Mandach, Ursula

    2013-06-18

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ (1). Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 (2) and continuously modified by Schneider et al. in 1972 (3), can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data.

  19. Vasculogenesis and angiogenesis in the first trimester human placenta: An innovative 3D study using an immersive Virtual Reality system

    NARCIS (Netherlands)

    R.H.F. van Oppenraaij; A.H.J. Koning; B.A. Lisman; K. Boer; M.J.B. van den Hoff; P.J. van der Spek; E.A.P. Steegers; N. Exalto

    2009-01-01

    First trimester human villous vascularization is mainly studied by conventional two-dimensional (2D) microscopy. With this (2D) technique it is not possible to observe the spatial arrangement of the haemangioblastic cords and vessels, transition of cords into vessels and the transition of vasculogen

  20. Trypanosoma cruzi (Chagas' disease agent reduces HIV-1 replication in human placenta

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    Cappa Stella

    2008-07-01

    Full Text Available Abstract Background Several factors determine the risk of HIV mother-to-child transmission (MTCT, such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level. Results Simple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain, either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues. Conclusion Our results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence

  1. Chimerism of placenta-derived cells with maternal blood and umbilical cord blood cells%胎盘来源细胞与母血、脐血细胞的嵌合

    Institute of Scientific and Technical Information of China (English)

    莫峥; 盛宏霞; 韩忠朝; 徐曼; 田宠; 张斌; 陈虎

    2014-01-01

    背景:胎盘中含有丰富的细胞群,因其中 CD34+细胞含量高而受到越来越多学者的关注,有望成为临床造血干细胞移植治疗血液病及其他恶性疾病的新来源。  目的:探索胎盘来源细胞的数量、集落形成能力及其与母体的嵌合程度。  方法:采用健康足月剖腹产妇的胎盘,灌注法及组织块消化法收集胎盘中细胞;流式细胞仪检测胎盘及脐血中 CD34+细胞比例;培养细胞集落,定期观察集落形态并计数;序列特异性引物 PCR 扩增技术及序列特异性寡核苷酸探针方法检测胎盘、脐血和母亲外周血的HLA类型;短串联重复PCR方法检测胎盘细胞、脐血细胞和母亲外周血细胞的嵌合情况。  结果与结论:胎盘中 CD34+细胞数量明显优于脐血,且胎盘具有体外多种集落形成能力,集落形成良好,同时胎盘提取细胞中含有母体来源成分。提示胎盘中细胞数量及其基本生物学特性使其有潜力成为临床造血干细胞移植的新来源。%BACKGROUND:There are abundant cel populations in the placenta that attracts more and more attentions because of high content of CD34+cel s. It is expected to become a new source of hematopoietic stem cel s for the treatment of hematologic diseases and other malignant diseases. OBJECTIVE:To investigate the amount of cel s derived from placenta, their colony forming ability, and their chimerism analysis. METHODS:Five placentas obtained from five healthy ful-term cesarean women were treated with perfusion method and tissue digestion for the cel col ection. Flow cytometry was used to detect the proportion of CD34+cel s in the placenta and cord blood, fol owed by the culture of cel colonies as wel as regular observation of cel morphology and counting. PCR amplification with sequence-specific primers and sequence-specific oligonucleotide probes were used to examine HLA type of placenta, umbilical cord blood, and

  2. Cytokine expression in malaria-infected non-human primate placentas

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    M.M. Gicheru

    2012-06-01

    Full Text Available Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis-Plasmodium knowlesi (P. knowlesi H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA. Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-α and interleukin 12 (IL-12. Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-γ levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

  3. Ultrasound diagnosis and abnormal placenta and umbilical cord%胎盘和脐带及其异常的超声诊断

    Institute of Scientific and Technical Information of China (English)

    齐红梅

    2015-01-01

    胎盘是胎儿与母体之间进行营养和物质交换的重要器官,超声可以检查到胎盘的内部结构、胎盘与子宫壁的关系。%Placenta is important organs between fetal and maternal nutrition and material exchange, ultrasound can examine the relationship between the internal structure of the placenta, the placenta and the uterine wall.

  4. Trisomy 21- affected placentas highlight prerequisite factors for human trophoblast fusion and differentiation.

    Science.gov (United States)

    Malassiné, André; Frendo, Jean-Louis; Evain-Brion, Danièle

    2010-01-01

    Trophoblastic cell fusion is one essential step of the human trophoblast differentiation pathway and is a multifactorial and dynamic process finely regulated and still poorly known. Disturbances of syncytiotrophoblast formation are observed in numerous pathological clinical conditions such as preeclampsia, intrauterine growth retardation and trisomy 21. In this review, we summarize current knowledge of the different membrane proteins directly involved in trophoblastic cell fusion, which we identified by using the physiological model of primary culture of villous trophoblastic cells. Connexin 43 and gap junctional intercellular communication point to the role of molecular exchanges through connexin channels preceding membrane fusion. Zona occludens-1, which can interact with connexin 43, is also directly involved in trophoblast fusion. The recently identified fusogenic membrane retroviral envelop glycoproteins syncytin 1 (encoded by the HERV-W gene) and syncytin 2 (encoded by the FRD gene) and their receptors are major factors involved in human placental development . We describe the increasing number of factors promoting or inhibiting trophoblast fusion and differentiation and emphasize the role of human chorionic gonadotropin (hCG) and its receptor. Indeed, in trisomy 21 the dynamic process leading to membrane fusion is impaired due to an abnormal hCG signaling. This abnormal trophoblast fusion and differentiation in trisomy 21-affected placenta is reversible in vitro. Trisomy 21 trophoblastic cell culture may therefore be useful to identify the possible large number of prerequisite factors involved in trophoblast fusion, the limiting step of trophoblast differentiation.

  5. Establishment of an in vitro model of the human placental barrier by placenta slice culture and ussing chamber.

    Science.gov (United States)

    Song, Dianrong; Guo, Jie; Han, Fang; Zhang, Wei; Wang, Yanan; Wang, Yuhua

    2013-01-01

    Our purpose was to establish an in vitro model of the human placental barrier based on placenta slice culture and Ussing chamber. The villous morphology, beta-human chorionic gonadotropin (β-hCG), mRNA and efflux function of P-glycoprotein (P-gp), and the permeability of the fluorescent marker were confirmed. The results showed that syncytiotrophoblast cells with abundant endoplasmic reticulum and mitochondria were covered with a dense microvillus in the placenta slice. The β-hCG secretion levels in the Ussing chamber were 274.13 ± 13.52 mIU/mL at 5 h, significantly higher than that in the incubator 95.2 ± 13.14 mIU/mL, and β-hCG continued to secrete for 48 h. P-gp mRNA was expressed in the placenta slice. The Rho123 apparent permeability coefficient (Papp) value from maternal side to the fetal side was 26.34 ± 1.87 nm/s, but it was significantly increased, to 289.55 ± 6.02 nm/s after adding verapamil. The Rho123 efflux value was >2. The fluorescein Papp value was (3.42 ± 0.24) × 10(-3) nm/s. In contrast, the fluorescein isothiocyanate-dextran (FD70) Papp value was (3.93 ± 0.08) × 10(-5) nm/s. This indicates that the placenta slice in the Ussing chamber had the activity of a placenta, and can act as a valuable in vitro model of placental barrier.

  6. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts

    Science.gov (United States)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-08-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle-cell interactions itself.

  7. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts

    Science.gov (United States)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-01-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle–cell interactions itself. PMID:27877820

  8. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts.

    Science.gov (United States)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-08-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle-cell interactions itself.

  9. More than clinical waste? Placenta rituals among Australian home-birthing women.

    Science.gov (United States)

    Burns, Emily

    2014-01-01

    The discursive construction of the human placenta varies greatly between hospital and home-birthing contexts. The former, driven by medicolegal discourse, defines the placenta as clinical waste. Within this framework, the placenta is as much of an afterthought as it is considered the "afterbirth." In home-birth practices, the placenta is constructed as a "special" and meaningful element of the childbirth experience. I demonstrate this using 51 in-depth interviews with women who were pregnant and planning home births in Australia or had recently had home births in Australia. Analysis of these interviews indicates that the discursive shift taking place in home-birth practices from the medicalized model translates into a richer understanding and appreciation of the placenta as a spiritual component of the childbirth experience. The practices discussed in this article include the burial of the placenta beneath a specifically chosen plant, consuming the placenta, and having a lotus birth, which refers to not cutting the umbilical cord after the birth of the child but allowing it to dry naturally and break of its own accord. By shifting focus away from the medicalized frames of reference in relation to the third stage of labor, the home-birthing women in this study have used the placenta in various rituals and ceremonies to spiritualize an aspect of birth that is usually overlooked.

  10. [A Nude Mouse Model for Human Umbilical Cord Blood Transplantation

    Science.gov (United States)

    Lan, Jiongcai; Liu, Hongyu; Chen, Qiang; Yang, Chongli; Zhang, Zhimei

    2000-03-01

    To evaluate the hematopoietic potentiality and the migration and homing routine of separated as well as cryopreserved umbilical cord blood hematopoietic cells, the BALB/cnu(+) mice were used to establish a murine model. This can prepare for the clinical transplantation and the establishment of a large-scale cord blood bank. The result indicated that the hydroxyethyl starch (HES) sedimentation and DMSO step-by-step cryopreservation procedure resulted in only less losses of hematopoietic progenitor cells and also unharmful to the hematopietic potentiality. We can found evidence for successful transplantation in each mouse which received (1.0 - 2.0) x 10(7) separated or cryopresered hematopoietic cells from cord blood, which lasted for about fifty days. The results demonstrated that (1) HES sedimentation and DMSO cryopreservation procedure can keep the hematopoietic potentiality of cord blood, and so can be used to clinical transplantation or establishment of a cord blood bank; (2) Rich hematopoietic stem cells in human cord blood can cross the xenogenetic barriers and successfully engraft mice; (3) The hematopoietic cells migrated among bone marrow, liver, spleen, lung and kidney in the mice and homed to bone marrow by the end. Cryopreservation may influence the adhesion molecule on the hematopoietic cells and the homing behaviour, but not influence their hematopoietic potentiality.

  11. Effect of Exercise Training on Enos Expression, NO Production and Oxygen Metabolism in Human Placenta

    Science.gov (United States)

    Ramírez-Vélez, Robinson; Bustamante, Juanita; Czerniczyniec, Analia; Aguilar de Plata, Ana C.; Lores-Arnaiz, Silvia

    2013-01-01

    Objective To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS), nitric oxide (NO) production and oxygen metabolism in human placenta. Methods The study included 20 nulliparous in gestational week 16–20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10) took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55–75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each) using barbells (1–3 kg/exercise) and low-to-medium resistance bands. The control group (n = 10) undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. Results Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05). Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05). Conclusion Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of

  12. Comparison of the levels of the growth factors in umbilical cord serum and human milk and its clinical significance.

    Science.gov (United States)

    Patki, Satish; Patki, Ujjwala; Patil, Rajendra; Indumathi, S; Kaingade, Pankaj; Bulbule, Akshata; Nikam, Amar; Pishte, Amit

    2012-08-01

    The process of the growth of the fetus begins in the uterus and gets further accelerated following the birth, especially during initial few months. The role of the growth factors in the physiology of the cellular growth is already well established. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) seem to be imperative for angiogenesis, cell development and proliferation as well as maintenance of the tissues. The levels of these factors in the maternal serum during pregnancy as well as during postpartum period are insignificant. Consequently, we hypothesized that the fetus receives moderate supply of these growth factors from the placenta during its stay in the uterus. This supply gets further augmented during the postpartum period through the different source, i.e. mother's milk. To study this physiological transition of the source of the growth factors from the placenta to the breast milk, the concentrations of VEGF and HGF in the cord serum of full term neonates and that in the breast milk of the corresponding mothers were analyzed during ELISA. The human milk, especially the colostrum revealed significantly higher levels of VEGF and HGF (1541.759 ± 119.349 pg/ml and 7129.249 ± 273.472 pg/ml) than cord serum (16.632 ± 0.773 pg/ml and 2581.6 ± 108.275 pg/ml) respectively. The multifold higher levels of VEGF observed in colostrum probably correlates with its high neonatal requirement for the maturation of the gastrointestinal epithelium following birth. The higher levels of both the growth factors in the breast milk than those observed in the cord serum probably explain their higher needs by the neonates for immunological protection, protein synthesis and neurocognitive development. The observations of the present study strengthen the policy of the colostrum feeding, which is promoted by organizations like World Health Organization (WHO). This study further documents the fact that the commercial milk formulae cannot replace the human

  13. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts.

    Science.gov (United States)

    Chen, Baosheng; Tuuli, Methodius G; Longtine, Mark S; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D

    2012-05-15

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.

  14. Expression of Androgen Receptor in Human Placentas from Normal and Preeclamptic Pregnancies

    Directory of Open Access Journals (Sweden)

    Te-Yao Hsu

    2009-09-01

    Conclusion: These data suggest that the increased AR expression may alter AR-mediated function on syncytiotrophoblasts and stromal cells in PE placentas, and be a possible mechanism for its association with preeclampsia.

  15. Morphological study of human heart and placenta in the first trimester of prenatal period of ontogenesis

    OpenAIRE

    Abdul-Ogly L.V.

    2008-01-01

    Probability of abnormal development is high in certain periods when the increased sensitiveness of embryo and fetus takes place. Influence of damaging factors as maternal infection and, consequently, fetal infection is a reason of abnormal development. Morphological characteristics of heart and placenta were studied during the first trimester of prenatal period of ontogenesis. 17 embryos, fetuses and placenta of 4-12 weeks were used. Abortions were made according to medical statements or mate...

  16. High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta

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    Clark Taane G

    2010-04-01

    Full Text Available Abstract Background Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. Results Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%. Conclusions Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes

  17. Detection of vitamin D binding protein on the surface of cytotrophoblasts isolated from human placentae

    Energy Technology Data Exchange (ETDEWEB)

    Nestler, J.E.; McLeod, J.F.; Kowalski, M.A.; Strauss, J.F. 3d.; Haddad, J.G. Jr.

    1987-05-01

    Vitamin D binding protein (DBP), a Mr 56,000-58,000 alpha 2-glycoprotein, is the major serum protein involved in the transport of vitamin D sterols. Recently it has been suggested that DBP may also be involved in immunoglobulin G binding to cells. Because the trophoblast is involved in the transport of molecules such as vitamin D and immunoglobulin G to the fetus, we asked whether DBP could be detected on the surface of human placental trophoblast cells. Cytotrophoblasts purified from human term placentae were fixed and made permeant with Triton X-100 and examined by indirect immunofluorescence after incubation with a monoclonal antibody to DBP. Greater than 90% of these cells stained positively, whereas no staining was observed with nonimmune antiserum. The presence of DBP on/in the surface of cytotrophoblasts could also be demonstrated by fluorescent cytometry. When cell surface-associated proteins of cytotrophoblasts were radioiodinated, a Mr 57,000 radiolabeled protein could be immunoisolated from the cell lysate with a purified monospecific polyclonal antibody to DBP. Immunoisolation of this radiolabeled protein was prevented by the addition of excess unlabeled human DBP to the cell lysate before incubation with antibody. This Mr 57,000 radiolabeled protein could also be isolated by affinity chromatography selecting for proteins that bind to globular actin. When cytotrophoblasts were incubated with (/sup 35/S)methionine for 3 or 18 h, active synthesis of DBP could not be demonstrated by immunoisolation techniques. These studies demonstrate the presence of DBP on the surface of well washed, human cytotrophoblasts. This DBP may be maternally derived, since active synthesis of DBP could not be demonstrated.

  18. Expansion of human cord blood hematopoietic stem cells for transplantation.

    Science.gov (United States)

    Chou, Song; Chu, Pat; Hwang, William; Lodish, Harvey

    2010-10-08

    A recent Science paper reported a purine derivative that expands human cord blood hematopoietic stem cells in culture (Boitano et al., 2010) by antagonizing the aryl hydrocarbon receptor. Major problems need to be overcome before ex vivo HSC expansion can be used clinically.

  19. Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats.

    Science.gov (United States)

    Chung, Hyo-jin; Chung, Wook-hun; Lee, Jae-Hoon; Chung, Dai-Jung; Yang, Wo-Jong; Lee, A-Jin; Choi, Chi-Bong; Chang, Hwa-Seok; Kim, Dae-Hyun; Suh, Hyun Jung; Lee, Dong-Hun; Hwang, Soo-Han; Do, Sun Hee; Kim, Hwi-Yool

    2016-03-01

    We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.

  20. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Machaalani, R., E-mail: rita.machaalani@sydney.edu.au [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Ghazavi, E. [Bosch Institute, The University of Sydney, NSW 2006 (Australia); School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Hinton, T. [School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Waters, K.A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Hennessy, A. [School of Medicine, University of Western Sydney, NSW 2751 (Australia); Heart Research Institute, 7 Eliza St Newtown, NSW 2042 (Australia)

    2014-05-01

    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.

  1. Stereological Changes of Human Placenta in Systemic Lupus Erythematosus Compared with Healthy Controls

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    Zahra Heidari

    2013-07-01

    Full Text Available Background: Systemic lupus erythematosus (SLE is a chronic autoimmune disease that can cause changes in the placenta. In this study, quantitative changes of placenta were investigated using stereological methods.Materials and Methods: In this case-control study, 10 placentas from systemic lupus erythematosus pregnancy (antinuclear antibody>10, and 10 placentas from normal uncomplicated pregnancy were obtained from Imam Ali Hospital. Volume of placentas was estimated using Cavalieri's principle. 3 full-thickness columns of each placenta were taken using systematic uniform random sampling (SURS. After fixation in modified Lillie's solution, they were cut into 5 mm slices. 5-7 sections selected from each slice using SURS and stained by Masson’s trichrome. Then stereological analyses were done on 8-10 SURS fields of each section. Placental volume, absolute volume and volume density of chorionic villi, intervillous space, syncytiotrophoblast, fibrin and blood vessels in chorionic villi were estimated in both groups. The Mann Whitney-U test was employed to determine statistically significant differences between the means. Significant level was set at p<0.05.Results: Total volume and volume density of fibrin and total volume and volume density of blood vessels significantly increased in SLE group in comparison with control group (p<0.01. Volume density of syncytiotrophoblast increased 50% in SLE group in comparison with control group, this increase was statistically significant (p<0.01.Conclusion: Results showed that systemic lupus erythematosus disease can cause significant changes in the structure of placenta that may be influential on the evolution and survival of fetus.

  2. GESTATIONAL DIABETES MELLITUS ALTERS APOPTOTIC AND INFLAMMATORY GENE EXPRESSION OF TROPHOBASTS FROM HUMAN TERM PLACENTA

    Science.gov (United States)

    MAGEE, Thomas R.; ROSS, Michael G.; WEDEKIND, Lauren; DESAI, Mina; KJOS, Siri; BELKACEMI, Louiza

    2014-01-01

    AIM Increased placental growth secondary to reduced apoptosis may contribute to the development of macrosomia in GDM pregnancies. We hypothesize that reduced apoptosis in GDM placentas is caused by dysregulation of apoptosis related genes from death receptors or mitochondrial pathway or both to enhance placental growth in GDM pregnancies. METHODS Newborn and placental weights from women with no pregnancy complications (controls; N=5), or with GDM (N=5) were recorded. Placental villi from both groups were either fixed for TUNEL assay, or snap frozen for gene expression analysis by apoptosis PCR microarrays and qPCR. RESULTS Maternal, placental and newborn weights were significantly higher in the GDM group vs. Controls. Apoptotic index of placentas from the GDM group was markedly lower than the Controls. At a significant threshold of 1.5, seven genes (BCL10, BIRC6, BIRC7, CASP5, CASP8P2, CFLAR, and FAS) were down regulated, and 13 genes (BCL2, BCL2L1, BCL2L11, CASP4, DAPK1, IκBκE, MCL1, NFκBIZ, NOD1, PEA15, TNF, TNFRSF25, and XIAP) were unregulated in the GDM placentas. qPCR confirmed the consistency of the PCR microarray. Using Western blotting we found significantly decreased placental pro-apoptotic FAS receptor and FAS ligand (FASL), and increased mitochondrial anti-apoptotic BCL2 post GDM insult. Notably, caspase-3, which plays a central role in the execution-phase of apoptosis, and its substrate poly (ADP-ribose) polymerase (PARP) were significantly down regulated in GDM placentas, as compared to non-diabetic Control placentas. CONCLUSION . Women with gestational diabetes (GDM) are at increased risk for having macrosomic newborns, and larger placentas with reduced apoptosis. Decreased apoptosis subsequent to alterations in apoptotic and inflammatory genes may promote elevated weight in the GDM placentas. PMID:24768206

  3. Isolation of cellular lipid droplets: two purification techniques starting from yeast cells and human placentas.

    Science.gov (United States)

    Mannik, Jaana; Meyers, Alex; Dalhaimer, Paul

    2014-04-01

    Lipid droplets are dynamic organelles that can be found in most eukaryotic and certain prokaryotic cells. Structurally, the droplets consist of a core of neutral lipids surrounded by a phospholipid monolayer. One of the most useful techniques in determining the cellular roles of droplets has been proteomic identification of bound proteins, which can be isolated along with the droplets. Here, two methods are described to isolate lipid droplets and their bound proteins from two wide-ranging eukaryotes: fission yeast and human placental villous cells. Although both techniques have differences, the main method-- density gradient centrifugation--is shared by both preparations. This shows the wide applicability of the presented droplet isolation techniques. In the first protocol, yeast cells are converted into spheroplasts by enzymatic digestion of their cell walls. The resulting spheroplasts are then gently lysed in a loose-fitting homogenizer. Ficoll is added to the lysate to provide a density gradient, and the mixture is centrifuged three times. After the first spin, the lipid droplets are localized to the white-colored floating layer of the centrifuge tubes along with the endoplasmic reticulum (ER), the plasma membrane, and vacuoles. Two subsequent spins are used to remove these other three organelles. The result is a layer that has only droplets and bound proteins. In the second protocol, placental villous cells are isolated from human term placentas by enzymatic digestion with trypsin and DNase I. The cells are homogenized in a loose-fitting homogenizer. Low-speed and medium-speed centrifugation steps are used to remove unbroken cells, cellular debris, nuclei, and mitochondria. Sucrose is added to the homogenate to provide a density gradient and the mixture is centrifuged to separate the lipid droplets from the other cellular fractions. The purity of the lipid droplets in both protocols is confirmed by Western Blot analysis. The droplet fractions from both preps

  4. Influence of low temperature storage on the properties of human placenta extracts

    Directory of Open Access Journals (Sweden)

    Ekaterina D. Rozanova

    2012-06-01

    Full Text Available Objective: This research represents the results of comparative investigations of the composition and biological activity of aqueous-saline extracts, obtained from fresh and stored at –196ºC human placental tissues. Methods: The studying of quantitative composition of proteins in human placenta extract (HPE was performed with gel-chromatography method. Content of lipid peroxidation products and catalase activity in the extracts were evaluated using spectrophotometric assay. Biological activity of extracts was evaluated by studying the modifications of structural and functional parameters of erythrocytes after exposure with the extracts. Results: Our researches have shown that properties of HPE from the stored at –196ºС tissues slightly differ from those of fresh tissues. In extract of frozen tissues the content of high-molecular proteins is relatively higher. Content of malonyldialdehyde in extracts of the tissues stored at –196ºC does not change. Catalase activity decreases. For evaluation of biological effect of the extract on erythrocytes we have analyzed the following structural and functional parameters of red blood cells: spontaneous hemolysis, osmotic, and low-pH resistances, which characterize mechanical properties and stability of cellular membranes; relative content of main forms of hemoglobin (oxy-, deoxy-, and met-Hb, which elucidate the functioning of biochemical systems; and cytosol microviscosity, which reflects structure-dynamical state, determined, first of all, by interaction of cytosol and components of cytoskeleton with membranes. Conclusion: It was shown that distinctions between the effects of extracts on erythrocytes were mainly manifested at cellular membrane level, not affecting main vital parameters. [J Exp Integr Med 2012; 2(3.000: 213-217

  5. Endoplasmic reticulum stress is induced in the human placenta during labour.

    Science.gov (United States)

    Veerbeek, J H W; Tissot Van Patot, M C; Burton, G J; Yung, H W

    2015-01-01

    Placental endoplasmic reticulum (ER) stress has been postulated in the pathophysiology of pre-eclampsia (PE) and intrauterine growth restriction (IUGR), but its activation remains elusive. Oxidative stress induced by ischaemia/hypoxia-reoxygenation activates ER stress in vitro. Here, we explored whether exposure to labour represents an in vivo model for the study of acute placental ER stress. ER stress markers, GRP78, P-eIF2α and XBP-1, were significantly higher in laboured placentas than in Caesarean-delivered controls localised mainly in the syncytiotrophoblast. The similarities to changes observed in PE/IUGR placentas suggest exposure to labour can be used to investigate induction of ER stress in pathological placentas. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. The multidrug resistance 1 gene Abcb1 in brain and placenta: comparative analysis in human and guinea pig.

    Science.gov (United States)

    Pappas, Jane J; Petropoulos, Sophie; Suderman, Matthew; Iqbal, Majid; Moisiadis, Vasilis; Turecki, Gustavo; Matthews, Stephen G; Szyf, Moshe

    2014-01-01

    The Multidrug Resistance 1 (MDR1; alternatively ABCB1) gene product P-glycoprotein (P-gp), an ATP binding cassette transporter, extrudes multiple endogenous and exogenous substrates from the cell, playing an important role in normal physiology and xenobiotic distribution and bioavailability. To date, the predominant animal models used to investigate the role of P-gp have been the mouse and rat, which have two distinct genes, Abcb1a and Abcb1b. In contrast, the human has a single gene, ABCB1, for which only a single isoform has been validated. We and others have previously shown important differences between Abcb1a and Abcb1b, limiting the extrapolation from rodent findings to the human. Since the guinea pig has a relatively long gestation, hemomonochorial placentation and neuroanatomically mature offspring, it is more similar to the human, and may provide a more comparable model for investigating the regulation of P-gp in the brain and placenta, however, to date, the Abcb1 gene in the guinea pig remains to be characterized. The placenta and fetal brain are barrier sites that express P-gp and that play a critical role of protection of the fetus and the fetal brain from maternally administered drugs and other xenobiotics. Using RNA sequencing (RNA-seq), reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR (QPCR) to sequence the expressed isoforms of guinea pig Abcb1, we demonstrate that like the human, the guinea pig genome contains one gene for Abcb1 but that it is expressed as at least three different isoforms via alternative splicing and alternate exon usage. Further, we demonstrate that these isoforms are more closely related to human than to rat or mouse isoforms. This striking, overall similarity and evolutionary relatedness between guinea pig Abcb1 and human ABCB1 indicate that the guinea pig represents a relevant animal model for investigating the function and regulation of P-gp in the placenta and brain.

  7. HISTOPATHOLOGICAL AND GROSS ANATOMICAL STUDY OF HUMAN PLACENTA IN PATIENTS WITH PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Vimla Kumari

    2016-07-01

    Full Text Available BACKGROUND The beginning reason for preeclampsia is the placenta. Preeclampsia starts to lessen with the conveyance of the placenta and can happen without a baby, however, with the nearness of trophoblast tissue with hydatidiform moles. In perspective of this, investigation of the placenta ought to give knowledge into the pathophysiology of preeclampsia. In this presentation, we look at placental pathological and anatomical changes with preeclampsia and Foetal Development Limitation (FGR. No doubt, this examination ought to enlighten as both conditions are associated with comparably unusual placentation yet just in preeclampsia is there a maternal pathophysiological disorder. Comparative bits of knowledge about ahead of schedule and late onset preeclampsia ought to likewise be given by such information. METHODS A prospective study was led in the Department of Obstetrics and Gynaecology, Government Medical College, Bettiah. 250 instances of pregnancy actuated hypertension were concentrated on. The cases with systolic circulatory strain more prominent than 130 mmHg, diastolic pulse more noteworthy than 90 mmHg on two estimations dismantled 6 hours in relationship with histological finding were incorporated into the study. These cases were further separated as mild preeclampsia if the diastolic circulatory strain was ≤100 mmHg and as moderate preeclampsia if the diastolic pulse was 110 mmHg. Extreme cases were characterised if the systolic pulse - ≥160 mmHg, diastolic circulatory strain ≥110 mmHg. Maternal and foetal result was considered and post conveyance placenta was sent for histopathologic examination. Gross anatomical and microscopic examination was done and discoveries were connected with the seriousness of PIH. RESULTS Out of 250 cases, there were 156 instances of mild PIH, 53 moderate and 41 were of severe PIH. On gross examination (Table 1, the mean weight of placenta was 429.9 gm in gentle instances of PIH, 364 gm in moderate

  8. Transplacental transfer of monomethyl phthalate and mono(2-ethylhexyl) phthalate in a human placenta perfusion system

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E; Hedegaard, Morten;

    2007-01-01

    and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 microg/L, respectively. The placental transfer was followed...... plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended....

  9. Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation

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    C. M. Raynaud

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC and fetal membrane (Mb-MSC through morphological and fluorescent-activated cell sorting (FACS. MSC frequency is higher in membrane than placenta (2.14%  ± 0.65 versus 15.67%  ± 0.29%. Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.

  10. IGF-IR signal transduction protein content and its activation by IGF-I in human placentas: relationship with gestational age and birth weight.

    Science.gov (United States)

    Iñiguez, Germán; Castro, Juan José; Garcia, Mirna; Kakarieka, Elena; Johnson, M Cecilia; Cassorla, Fernando; Mericq, Verónica

    2014-01-01

    The human placenta expresses the IGF-I and IGF-IR proteins and their intracellular signal components (IRS-1, AKT and mTOR). The aim of this study was to assess the IGF-IR content and activation of downstream signaling molecules in placentas from newborns who were classified by gestational age and birth weight. We studied placentas from 25 term appropriate (T-AGA), 26 term small (T-SGA), 22 preterm AGA (PT-AGA), and 20 preterm SGA (PT-SGA) newborns. The total and phosphorylated IGF-IR, IRS-1, AKT, and mTOR contents were determined by Western Blot and normalized by actin or with their respective total content. The effect of IGF-I was determined by stimulating placental explants with recombinant IGF-I 10-8 mol/L for 15, 30, and 60 minutes. The IGF-IR content was higher in T-SGA compared to T-AGA placentas, and the IRS-1 content was higher in PT-placentas compared with their respective T-placentas. The effect of IGF-I on the phosphorylated forms of IGF-IR was increased in T-SGA (150%) and PT-SGA (300%) compared with their respective AGA placentas. In addition, AKT serine phosphorylation was higher in PT-SGA compared to PT-AGA and T-SGA placentas (90% and 390% respectively). The higher protein content and response to IGF-I of IGF-IR, IRS-1, and AKT observed in SGA placentas may represent a compensatory mechanism in response to fetal growth restriction.

  11. IGF-IR signal transduction protein content and its activation by IGF-I in human placentas: relationship with gestational age and birth weight.

    Directory of Open Access Journals (Sweden)

    Germán Iñiguez

    Full Text Available The human placenta expresses the IGF-I and IGF-IR proteins and their intracellular signal components (IRS-1, AKT and mTOR. The aim of this study was to assess the IGF-IR content and activation of downstream signaling molecules in placentas from newborns who were classified by gestational age and birth weight. We studied placentas from 25 term appropriate (T-AGA, 26 term small (T-SGA, 22 preterm AGA (PT-AGA, and 20 preterm SGA (PT-SGA newborns. The total and phosphorylated IGF-IR, IRS-1, AKT, and mTOR contents were determined by Western Blot and normalized by actin or with their respective total content. The effect of IGF-I was determined by stimulating placental explants with recombinant IGF-I 10-8 mol/L for 15, 30, and 60 minutes.The IGF-IR content was higher in T-SGA compared to T-AGA placentas, and the IRS-1 content was higher in PT-placentas compared with their respective T-placentas. The effect of IGF-I on the phosphorylated forms of IGF-IR was increased in T-SGA (150% and PT-SGA (300% compared with their respective AGA placentas. In addition, AKT serine phosphorylation was higher in PT-SGA compared to PT-AGA and T-SGA placentas (90% and 390% respectively.The higher protein content and response to IGF-I of IGF-IR, IRS-1, and AKT observed in SGA placentas may represent a compensatory mechanism in response to fetal growth restriction.

  12. Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum.

    Science.gov (United States)

    Naruki, M; Mizutani, S; Goto, K; Tsujimoto, M; Nakazato, H; Itakura, A; Mizuno, K; Kurauchi, O; Kikkawa, F; Tomoda, Y

    1996-01-01

    The hydrolysis of oxytocin (OT) by human placental subcellular fractions and pregnant sera was studied in the presence of bestatin, a potent inhibitor of aminopeptidases, and the antibody against pregnant serum oxyotocinase (P-LAP)(EC 3.4 11.3) by measuring liberated amino acids by high performance liquid chromatography (HPLC). Our immunotitration study and the effect of bastatin on the oxytocin-degrading protease showed that the initiating and responsible protease in oxyotocin degradation in human placenta and pregnant serum is P-LAP.

  13. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy.

    Science.gov (United States)

    Morales, Eva; Vilahur, Nadia; Salas, Lucas A; Motta, Valeria; Fernandez, Mariana F; Murcia, Mario; Llop, Sabrina; Tardon, Adonina; Fernandez-Tardon, Guillermo; Santa-Marina, Loreto; Gallastegui, Mara; Bollati, Valentina; Estivill, Xavier; Olea, Nicolas; Sunyer, Jordi; Bustamante, Mariona

    2016-10-01

    We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach. Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [false discovery rate (FDR) < 0.05]. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight. We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International

  14. Characteristics of glucose transport across the microvillous membranes of human term placenta

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    Ravinderjit Kaur Anand

    Full Text Available Transport characteristics of D-glucose were studied in the microvillous vesicles isolated from the human term placenta. Transport occurred by selective and rapid facilitated diffusion system which was inhibitable by phloretin and HgCl2. The transport was dependent on a transmembrane. Na+-gradient indicating a "secondary active transport" system operating. The transport influx was saturable and the kinetic analysis based on Hanes-Woolf plot produced a kt and Jmax value of 1.2 mM and 34 nmoles. mgprotein-1.min-1, respectively. The efflux of D-glucose from the membrane vesicles in a pre-equilibrated assay conditions showed a distinct biphasic pattern differing significantly in the half time efflux. The t1/2 of the fast and slow components was found to be 15 sec and 660 sec, respectively. The transport showed distinct sensitivity to temperature and the Ea values both below and above the transition temperature of 37 ºC, as calculated from the Arrhenius plot were found to be 7600 and 5472 kCa1.mol-1, respectively. Inhibition studies with a number of sugars for hexose transport pathway showed that the glucose epimers, phosphorylated sugars, and even the disaccharides and the pentose sugars competed effectively with D-glucose. The influx was also inhibited by a number of steroids such as progesterone, 17α-hydroxyprogesterone, testosterone and estrogen. Insulin was found to increase glucose transport in a dose- dependent fashion at a concentration of 0.2-1 unit.ml-1. Ouabain, dinitrophenoi and nicotine strongly inhibited D-glucose uptake in the membrane vesicles.

  15. Identification and localization of netrin-4 and neogenin in human first trimester and term placenta.

    Science.gov (United States)

    Dakouane-Giudicelli, M; Duboucher, C; Fortemps, J; Salama, S; Brulé, A; Rozenberg, P; de Mazancourt, P

    2012-09-01

    We describe here for the first time the characterization of family member of netrins, netrin-4 and its receptor neogenin, during the development of the placenta. By using western blots and RT-PCR, we demonstrated the presence of netrin-4 and its receptor neogenin protein as well as their transcripts. Using immunohistochemistry, we studied the distribution of netrin-4 and neogenin in both the first trimester and term placenta. We observed staining of netrin-4 in villous and extravillous cytotrophoblasts, syncytiotrophoblast, and endothelial cells whereas staining in stromal cells was faint. In decidua, we observed netrin-4 labelling in glandular epithelial cells, perivascular decidualized cells, and endothelial cells. However, neogenin was absent in villous and extravillous cytotrophoblasts and was expressed only on syncytiotrophoblast and placental stromal cells in the first trimester and at term placenta. The pattern of distribution suggests that a functional netrin-4-neogenin pathway might be restricted to syncytiotrophoblasts, mesenchymal cells, and villous endothelial cells. This pathway function might vary with its localization in the placenta. It is possibly involved in angiogenesis, morphogenesis, and differentiation.

  16. Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone

    Science.gov (United States)

    Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

    2011-01-01

    Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

  17. Low expression of soluble human leukocyte antigen G in early gestation and subsequent placenta-mediated complications of pregnancy.

    Science.gov (United States)

    Marozio, Luca; Garofalo, Anna; Berchialla, Paola; Tavella, Anna Maria; Salton, Loredana; Cavallo, Franco; Benedetto, Chiara

    2017-07-10

    Abnormal placentation is a common pathogenic mechanism of many placenta-mediated complications of late pregnancy, including pre-eclampsia, fetal growth restriction, stillbirth, and placental abruption. During successful placentation, the trophoblast (which is a semi-allograft) is not rejected by decidual immune cells because of maternal immune tolerance, mainly induced by human leukocyte antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the development of complications of pregnancy. The aim of this study was to determine whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of pregnancy may be associated with subsequent placenta-mediated complications. For this retrospective case-control study, 117 cases of placenta-mediated complications of pregnancy and 234 controls with uneventful pregnancy were selected. Plasma sHLA-G levels were measured at 11-13 weeks' gestation by the enzyme-linked immunosorbent assay method in blood samples previously obtained at first-trimester prenatal screening for chromosomal fetal abnormalities. Women who subsequently developed placenta-mediated complications had significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08 IU/mL) than controls (median, 49.10 IU/mL; P = 0.008). An sHLA-G level lower than 43.50 IU/mL at the end of the first trimester was associated with a twofold increased risk of developing a pregnancy complication (odds ratio, 1.82; 95% confidence interval, 1.22-2.73). The strongest association, although only moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95% confidence interval, 1.08-6.56). Placenta-mediated complications of pregnancy may be associated with low sHLA-G levels in the first trimester, suggesting a potential role of sHLA-G in the early stages of placentation. © 2017 Japan Society of Obstetrics and Gynecology.

  18. Traumatic spinal cord injury in mice with human immune systems.

    Science.gov (United States)

    Carpenter, Randall S; Kigerl, Kristina A; Marbourg, Jessica M; Gaudet, Andrew D; Huey, Devra; Niewiesk, Stefan; Popovich, Phillip G

    2015-09-01

    Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rg(null) (NSG) mice engrafted with human CD34(+) hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in the blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI

  19. Nuclear factor-κB mediates placental growth factor induced pro-labour mediators in human placenta.

    Science.gov (United States)

    Lappas, Martha

    2012-07-01

    Prostaglandins, pro-inflammatory cytokines, extracellular matrix remodelling enzymes and nuclear factor-kappa B (NF-κB) are involved in the mechanisms of term and preterm parturition. Recent studies have reported an increase in angiogenesis-related genes during term and preterm labour, including placental growth factor (PLGF). In non-gestational tissues, PLGF induces inflammation via NF-κB. The aim of this study was to determine the effect of PLGF on the gene expression and release of pro-labour mediators in human placenta. Samples were obtained from normal pregnancies at the time of Caesarean section. Human placenta was incubated in the absence (basal control) or presence of a 10 ng/ml PLGF for 24 h. Inflammatory gene expression was analysed by quantitative RT-PCR, concentration of pro-inflammatory cytokines and prostaglandins was quantified by ELISA, and secretory matrix metalloproteinases (MMPs) activity by zymography. NF-κB DNA-binding activity and IκB-α (inhibitor of NF-κB) protein degradation were analysed by ELISA and Western blotting, respectively. PLGF significantly increased interleukin (IL)-6 and IL-8 gene expression and secretion, cyclooxygenase-2 expression and resultant prostaglandin (PG) E(2) and PGF(2α) release, and MMP-9 gene expression and enzyme production. PLGF induced the degradation of IκB-α whilst increasing NF-κB p65 DNA-binding activity. The PLGF-induced pro-labour responses were abrogated by co-treatment with the NF-κB inhibitor BAY 11-7082. In summary, the pro-inflammatory and pro-labour effects of PLGF in human placenta are mediated by NF-κB.

  20. Dynamic change of Adamalysin 19 (ADAM19) in human placentas and its effects on cell invasion and adhesion in human trophoblastic cells

    Institute of Scientific and Technical Information of China (English)

    SANG; QingXiang; Amy

    2009-01-01

    Human ADAM19 is a recently identified member of the ADAM family.It is highly expressed in human placentas,but its dynamic change and function at the human feto-maternal interface during placentation remain to be elucidated.In this present study,the spatial and temporal expression and cellular localization of ADAM19 in normal human placentas were first demonstrated,and the effects of ADAM19 on trophoblast cell adhesion and invasion were further investigated by using a human choriocarcinoma cell line(JEG-3) as an in vitro model.The data demonstrated that ADAM19 was widely distributed in villous cytotrophoblast cells,syncytiotrophoblast cells,column trophoblasts,and villous capillary endothelial cells during early pregnancy.The mRNA and protein level of ADAM19 in placentas was high at gestational weeks 8-9,but diminished significantly at mid-and term pregnancy.In JEG-3 cells,the overexpression of ADAM19 led to diminished cell invasion,as well as increases in cell adhesiveness and the expression of E-cadherin,with no changes in β-catenin expression observed.These data indicate that ADAM19 may participate in the coordinated regulation of human trophoblast cell behaviors during the process of placentation.

  1. Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle.

    Science.gov (United States)

    Tran, Ha T; Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-01-01

    Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

  2. Comparing the Effect of Topical Application of Human Milk and Dry Cord Care on Umbilical Cord Separation Time in Healthy Newborn Infants

    Directory of Open Access Journals (Sweden)

    Azar Aghamohammadi

    2012-06-01

    Full Text Available Objective: Comparing the effect of topical human milk application and dry cord care on cord separation time.Methods: This research was a randomized clinical trial study on 130 singleton and mature newborns.Newborns were placed randomly in groups of topical application of human milk and dry cord care. Theumbilical separation time was compared in the two groups. Data was analyzed by SPSS software. Independent Samples t-Test, χ2, Fisher were used in this study.Findings: Median time of cord separation in human milk application group (150.95±28.68 hours was significantly shorter than dry cord care group (180.93±37.42 hours (P<0.001.Conclusion: Topical application of human milk on the remaining part of the cord reduces the cord separation time and it can be used as an easy, cheap and non invasive way for cord care.

  3. Expression of Hepcidin and Ferroportin in the Placenta, and Ferritin and Transferrin Receptor 1 Levels in Maternal and Umbilical Cord Blood in Pregnant Women with and without Gestational Diabetes

    Science.gov (United States)

    Yang, Anqiang; Zhao, Jun; Lu, Minhua; Gu, Ying; Zhu, Yunlong; Chen, Daozhen; Fu, Jinyan

    2016-01-01

    Background: Regulation of iron transfer from mother to fetus via the placenta is not fully understood and the relationship between stored iron status in the mothers’ serum and gestational diabetes (GDM) in case–control studies is controversial. The present study aimed to detect circulating soluble transferrin receptor (sTfR) and ferritin levels in maternal and umbilical cord blood. We also examined the expression of hepcidin (Hep), transferrin receptor (TfR1), and ferroportin (FPN) in the placenta in pregnant women with and without GDM at full term. Methods: Eighty-two women participated (42 with GDM and 40 without GDM [controls]). Maternal samples were collected at 37–39 weeks’ gestation. Umbilical cord blood was collected at birth. Ferritin and sTfR levels in maternal serum and umbilical cord blood, and Hep, TfR1, and FPN protein expression in plac enta were compared between the GDM and non-GDM groups. Serum ferritin (SF) was measured by electrochemiluminescence assay and sTfR was measured by ELISA. Hep, TfR1, and FPN expression was measured by immunohistochemistry. Results: Maternal serum sTfR levels were significantly elevated in the GDM group compared with the non-GDM group (p = 0.003). SF levels in cord blood in the GDM group were significantly higher than those in the non-GDM group (p = 0.003). However, maternal hemoglobin and SF, and umbilical cord sTfR levels were not different between the groups. In placental tissue, FPN expression was higher and hepcidin expression was lower in the GDM group compared with the non-GDM group (p = 0.000 and p = 0.044, respectively). There was no significant difference in TfR1 between the groups (p = 0.898). Conclusions: Women with GDM transport iron more actively than those without GDM at term pregnancy. Maternal iron metabolism in GDM may play a role in fetal/placental iron demand and in the overall outcome of pregnancy. PMID:27483296

  4. The cellular inflammatory response in human spinal cords after injury.

    Science.gov (United States)

    Fleming, Jennifer C; Norenberg, Michael D; Ramsay, David A; Dekaban, Gregory A; Marcillo, Alexander E; Saenz, Alvaro D; Pasquale-Styles, Melissa; Dietrich, W Dalton; Weaver, Lynne C

    2006-12-01

    Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were 'dead at the scene' or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1-3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil alpha-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1-3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1-3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8(+) lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative

  5. GnRH-II receptor-like antigenicity in human placenta and in cancers of the human reproductive organs.

    Science.gov (United States)

    Eicke, Nicola; Günthert, Andreas R; Viereck, Volker; Siebold, Doreen; Béhé, Martin; Becker, Tamara; Emons, Günter; Gründker, Carsten

    2005-10-01

    We have recently demonstrated that the antiproliferative activity of GnRH-II on human endometrial and ovarian cancer cell lines is not mediated through the GnRH-I receptor. A functional receptor for human GnRH-II has not yet been identified. In this study, we have generated a polyclonal antiserum to the putative human GnRH-II receptor using a peptide (YSPTMLTEVPPC) corresponding to the third extracellular domain coupled to keyhole limpet haemocyanin via the Cys residue. A database search showed no identical peptide sequences in any other human gene. To avoid cross-reactions against two similar amino acid sequences the antiserum was pre-absorbed using these peptides. Immune histological sections of human placenta and human endometrial, ovarian and prostate cancers using rabbit anti-human GnRH-II receptor antiserum showed GnRH-II receptor-like staining. Western blot analysis of cell membrane preparations of human endometrial and ovarian cancer cell lines yielded a band at approximately 43 kDa whereas Western blot analysis of cell membrane preparations of ovaries obtained from the marmoset monkey (Callithrix jacchus) yielded a band at approximately 54 kDa. To identify the GnRH-II receptor-like antigen we used the photo-affinity labelling technique. Photochemical reaction of (125)I-labelled (4-azidobenzoyl)-N-hydroxysuccinimide-[d-Lys(6)]-GnRH-II (10(-9) M) with cell membrane preparations of human endometrial and ovarian cancer cells yielded a band at approximately 43 kDa. In competition experiments, the GnRH-I agonist Triptorelin (10(-7) M) showed a weak decrease of (125)I-labelled (4-azidobenzoyl)-N-hydroxysuccinimide-[d-Lys(6)]-GnRH-II binding to its binding site. The GnRH-I antagonist Cetrorelix (10(-7) M) showed a clearly stronger decrease, whereas GnRH-II agonist [d-Lys(6)]-GnRH-II (10(-7) M) was the most potent competitor. Western blot analysis of the same gel using rabbit anti-human GnRH-II receptor antiserum identified this band as GnRH-II receptor

  6. Comparing the Effect of Topical Application of Human Milk and Dry Cord Care on Umbilical Cord Separation Time in Healthy Newborn Infants

    OpenAIRE

    Aghamohammadi, Azar; Zafari, Mandana; Moslemi, Leila

    2012-01-01

    Objective Comparing the effect of topical human milk application and dry cord care on cord separation time. Methods This research was a randomized clinical trial study on 130 singleton and mature newborns. Newborns were placed randomly in groups of topical application of human milk and dry cord care. The umbilical separation time was compared in the two groups. Data was analyzed by SPSS software. Independent Samples t-Test, χ2, Fisher were used in this study. Findings Median time of cord sepa...

  7. Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta.

    Science.gov (United States)

    Sardesai, Varda S; Shafiee, Abbas; Fisk, Nicholas M; Pelekanos, Rebecca A

    2017-04-01

    Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender-discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi-derived MSC (CV-MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV-MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070-1084.

  8. Isolation and comparative analysis of potential stem/progenitor cells from different regions of human umbilical cord

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    Naimisha Beeravolu

    2016-05-01

    Full Text Available Human umbilical cord (hUC blood and tissue are non-invasive sources of potential stem/progenitor cells with similar cell surface properties as bone marrow stromal cells (BMSCs. While they are limited in cord blood, they may be more abundant in hUC. However, the hUC is an anatomically complex organ and the potential of cells in various sites of the hUC has not been fully explored. We dissected the hUC into its discrete sites and isolated hUC cells from the cord placenta junction (CPJ, cord tissue (CT, and Wharton's jelly (WJ. Isolated cells displayed fibroblastoid morphology, and expressed CD29, CD44, CD73, CD90, and CD105, and showed evidence of differentiation into multiple lineages in vitro. They also expressed low levels of pluripotency genes, OCT4, NANOG, SOX2 and KLF4. Passaging markedly affected cell proliferation with concomitant decreases in the expression of pluripotency and other markers, and an increase in chondrogenic markers. Microarray analysis further revealed the differences in the gene expression of CPJ-, CT- and WJ-hUC cells. Five coding and five lncRNA genes were differentially expressed in low vs. high passage hUC cells. Only MAEL was expressed at high levels in both low and high passage CPJ-hUC cells. They displayed a greater proliferation limit and a higher degree of multi-lineage differentiation in vitro and warrant further investigation to determine their full differentiation capacity, and therapeutic and regenerative medicine potential.

  9. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, L.P. [Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Iglesias, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Nicola, F.C. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Steffens, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Valentim, L.; Witczak, A.; Zanatta, G. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Achaval, M. [Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Pranke, P. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Netto, C.A. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2011-12-23

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10{sup 6} cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10{sup 6} cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

  10. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    Directory of Open Access Journals (Sweden)

    L.P. Rodrigues

    2012-01-01

    Full Text Available Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a 1 h after surgery, into the injury site at a concentration of 5 x 10(6 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group; b into the cisterna magna, 9 days after lesion at a concentration of 5 x 10(6 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group. The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day. The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05. The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

  11. [Effect of homocysteine on the structure and functions of human placenta trophoblasts].

    Science.gov (United States)

    Martseniuk, O P; Romanets', K L; Obolens'ka, M Iu; Huppertz, B

    2009-01-01

    Elevated level of homocysteine in blood serum of pregnant women is the risk factor for placental malfunction and fetal abnormalities. Our study has shown the activation of apoptosis, inhibition of proliferation, destruction of placental trophoblast and activation of the transsulfuration pathway under elevated homocysteine level in the incubation medium in the range of 20-80 microM. The activation of the transsulfuration pathway indicates that placenta may to some extent withstand elevated homocysteine level.

  12. Monocarboxylate transporter 8 expression in the human placenta : the effects of severe intrauterine growth restriction

    OpenAIRE

    Chan, S-Y; Franklyn, J.A.; Pemberton, H. N.; Bulmer, J N; Visser, T.J.; McCabe, C. J.; Kilby, M. D.

    2006-01-01

    Thyroid hormones (THs) are essential for normal fetal development, with even mild perturbation in maternal thyroid status in early pregnancy being associated with neurodevelopmental delay in children. Transplacental transfer of maternal THs is critical, with increasing evidence suggesting a role for T3 in development and function of the placenta itself, as well as in development of the central nervous and other organ systems. Intrauterine growth restriction (IUGR) is associated with fetal hyp...

  13. Heat Shock Protein 70 Expression Is Spatially Distributed in Human Placenta and Selectively Upregulated during Labor and Preeclampsia

    Science.gov (United States)

    Abdulsid, Akrem; Hanretty, Kevin; Lyall, Fiona

    2013-01-01

    Placental oxidative stress is a feature of both human labor and the pregnancy syndrome preeclampsia. Heat shock proteins (HSPs) can be induced in cells as a protective mechanism to cope with cellular stress. We hypothesized that HSP 70 would increase during labor and preeclampsia and that expression would vary in different placental zones. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. Non-labor, labor and preeclampsia were studied. HSP 70 expression was investigated by Western blot analysis. HSP 70 protein expression was increased in the middle compared with the outer area (p = 0.03) in non-labor and in both the inner and middle areas compared with the outer area (p = 0.01 and p = 0.02 respectively) in labor. HSP 70 was increased in the preeclampsia non-labor group compared to the control non-labor group in the inner region (p = 0.003) and in the control labor group compared with the preeclampsia labor group at the middle area (p = 0.001). In conclusion HSP 70 is expressed in a spatial manner in the placenta. Changes in HSP 70 expression occur during labor and preeclampsia but at different zones within the placenta. The physiological and pathological significance of these remains to be elucidated but the results have important implications for how data obtained from studies in placental disease (and other organs) can be influenced by sampling methods. PMID:23382911

  14. Retroviral-mediated transfer and functional expression of multidrug resistance gene in human placenta mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    HAN Li-ying; YE Ming-zhu; LI Ya-ping; WANG Bo-wei; WANG Qiang; ZHAO Shu-hua; LI He-lian

    2008-01-01

    Background Most of gynecologic malignancies are sensitive to chemotherapy. Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdrl) gene is well known for its ability to confer drug resistance. This study aimed to explore the feasibility of expression and resistance of mdrl gene transduction into human placenta mesenchymal stem cells (P-MSCs) by retrovirus vector.Methods Human P-MSCs were isolated from trypsin-digested term placentas, and their immunophenotypes and differentiation potential were evaluated. Human P-MSCs were transduced by reconstructed retroviral vector containing the mdrl gene and green fluorescent protein (GFP) reporter gene. The integration and expression of the mdrl gene were observed indirectly by the expression of GFP, and fluorescence-activated cell sorter was used to evaluate the functional activity of permeability glycoprotein (P-gp) encoded by the mdrl gene. The stimulating test was made in vitro to show pleiotropic drug resistance of transfected cells.Results The isolated, cultured and expanded P-MSCs expressed stem cell markers such as CD29, CD44 and CD73,and showed osteogenic and adipogenic differentiation potentials under appropriate conditions. The expression of P-gp in the non-transfected P-MSCs cells was (0.4±0.1)%, but increased to (28.1±4.7)% after gene transfection (P<0.01). And positive staining of P-gp located mainly at cell membrane and cytoplasm. Accumulation and extrusion assays showed that P-gp expressed by the transfected cells had pump-functional activity and could efflux daunomycin out of cells. The analysis of cell survival confirmed that transfected P-MSCs had a characteristic of multidrug resistance with a significant increase in the resistance to anticancer agents.Conclusions Transfer and expression of human mdrl gene mediated by retrovirus vector conferred P-MSCs drug resistance. It might provide a new alternative to chemoprotection strategies.

  15. Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis

    DEFF Research Database (Denmark)

    Rindsjö, E; Hulthén Varli, I; Ofori, M F

    2006-01-01

    We have shown previously that numerous IgE(+) macrophage-like cells are present in the villous stroma of full term placenta and that there was no difference in the amount of IgE(+) cells between allergic and non-allergic mothers. The presence of such an abundant number of IgE(+) cells...... from Ghana with and without malaria parasites. The immunohistochemical staining pattern for IgE looked similar to our previous study, with the IgE located on Hofbauer-like cells. We could not find any difference in the amount or distribution of IgE(+) cells between malaria-infected and non...

  16. Trace elements determination by energy dispersive X-ray fluorescence (EDXRF) in human placenta and membrane: a comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Custodio, P.J.; Carvalho, M.L. [Centro Fisica Atomica, Universidade de Lisboa, Av. Prof. Gama Pinto, 2, 1649-003, Lisboa (Portugal); Nunes, F. [Hospital Garcia de Orta, Almada (Portugal)

    2003-04-01

    This work is an application of energy dispersive X-ray fluorescence (EDXRF) as an analytical technique for trace elemental determination in human membrane and placenta and elemental concentrations correlations in both tissues. Whole samples were collected during the delivery from healthy mothers and full-term pregnancies. The age of the mother was between 25 and 40 years old, and the weight of the infants ranged from 2.56 to 4.05 kg. Samples were lyophilised and analysed without any chemical treatment. No significant differences in elemental content of placenta and membrane samples were observed except for Ca. Very low levels of Se, As and Pb were observed in all the analysed samples. Zn, considered as one of the key elements in newborn health, was not significantly different in the analysed samples, all of which originated from healthy mothers and healthy babies. The obtained values agree with the literature except for Ca, which is much higher in the studied samples. (orig.)

  17. The pathology of human spinal cord injury: defining the problems.

    Science.gov (United States)

    Norenberg, Michael D; Smith, Jon; Marcillo, Alex

    2004-04-01

    This article reviews the pathology of human spinal cord injury (SCI), focusing on potential differences between humans and experimental animals, as well as on aspects that may have mechanistic or therapeutic relevance. Importance is placed on astrocyte and microglial reactions. These cells carry out a myriad of functions and we review the evidence that supports their beneficial or detrimental effects. Likewise, vascular responses and the role of inflammation and demyelination in the mechanism of SCI are reviewed. Lastly, schwannosis is discussed, highlighting its high frequency and potential role when designing therapeutic interventions. We anticipate that a better understanding of the pathological responses in the human will be useful to investigators in their studies on the pathogenesis and therapy of SCI.

  18. Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta

    Directory of Open Access Journals (Sweden)

    A Kittel

    2009-06-01

    Full Text Available Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/ CD39 is the dominant ecto-nucleotidase of vascular and placental trophoblastic tissues and appears to modulate the functional expression of type-2 purinergic (P2 Gprotein coupled receptors (GPCRs. Hence, this ectoenzyme could regulate nucleotide-mediated signalling events in placental tissue. This immunohistochemical and immuno-electron microscopic study demonstrates the expression of NTPDase1/CD39, P2Y1 and P2Y2 receptors in different cell types of human placenta. Specifically P2Y1 has an exclusive vascular distribution whereas P2Y2 is localized on trophoblastic villi. Co-localization of P2Y1 and NTPDase1/ CD39 are observed in caveolae, membrane microdomains of endothelial cells. The differential localization of these P2 receptors might indicate their unique roles in the regulation of extracellular nucleotide concentrations in human placental tissues and consequent effects on vascular tone and blood fluidity.

  19. Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

    Directory of Open Access Journals (Sweden)

    Frederiksen Marie

    2010-07-01

    Full Text Available Abstract Background Polybrominated diphenyl ethers (PBDEs have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very high concern due to critical windows in fetal development. Methods A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored in the maternal and fetal compartments. In addition, the perfused cotyledon, the surrounding placental tissue as well as pre-perfusion placental tissue and umbilical cord plasma were also analysed. The PBDE analysis included Soxhlet extraction, clean-up by adsorption chromatography and GC-MS analysis. Results and Discussion Placental transfer of BDE-47 was faster and more extensive than for BDE-99. The fetal-maternal ratios (FM-ratio after four hours of perfusion were 0.47 and 0.25 for BDE-47 and BDE-99, respectively, while the indicative permeability coefficient (IPC measured after 60 minutes of perfusion was 0.26 h-1 and 0.10 h-1, respectively. The transport of BDE-209 seemed to be limited. These differences between the congeners may be related to the degree of bromination. Significant accumulation was observed for all congeners in the perfused cotyledon as well as in the surrounding placental tissue. Conclusion The transport of BDE-47 and BDE-99 indicates in utero exposure to these congeners. Although the transport of BDE-209 was limited, however, possible metabolic debromination may lead to products which are both more toxic and transportable. Our study demonstrates fetal exposure to PBDEs, which should be included in risk assessment of PBDE exposure of women of child-bearing age.

  20. Gene expression analysis of the microdissected trophoblast layer of human placenta after the spontaneous onset of labor.

    Science.gov (United States)

    Kim, Soo Hyun; Shim, Sung Han; Sung, Se Ra; Lee, Kyung A; Shim, Jung Yun; Cha, Dong Hyun; Lee, Kyoung Jin

    2013-01-01

    Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown. Our goal in this study was to compare the mRNA expression pattern of the trophoblast layer of normal term placenta between women who had given natural birth (labor group) and those who had undergone an elective cesarean section without labor (non-labor group). We collected placental tissue samples from six pregnant women after term vaginal deliveries (labor group) and from six pregnant women after scheduled Cesarean sections (non-labor group). Frozen sections were made immediately after placental delivery. Because the placenta is a heterogeneous tissue composed of several cell types, we used laser capture microdissection to separate the trophoblast layer from the rest of the placental tissues. A number of genes were differentially expressed in the trophoblast layer when the labor and non-labor groups were compared. The expression of SIRT1, KAP1, and CRH was significantly lower in the trophoblast layer of the labor group than of the non-labor group. The expression of IL-1b, NF-kB1 and TLR 8 in the labor group was significantly higher than that in the non-labor group. Human term labor may be closely associated with inflammatory response. We suggest that downregulation of SIRT1, KAP1, and CRH gene expression in the trophoblast may play a key role in parturition and initiation of labor in pregnant human females.

  1. Gene expression analysis of the microdissected trophoblast layer of human placenta after the spontaneous onset of labor.

    Directory of Open Access Journals (Sweden)

    Soo Hyun Kim

    Full Text Available BACKGROUND: Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown. Our goal in this study was to compare the mRNA expression pattern of the trophoblast layer of normal term placenta between women who had given natural birth (labor group and those who had undergone an elective cesarean section without labor (non-labor group. METHODS: We collected placental tissue samples from six pregnant women after term vaginal deliveries (labor group and from six pregnant women after scheduled Cesarean sections (non-labor group. Frozen sections were made immediately after placental delivery. Because the placenta is a heterogeneous tissue composed of several cell types, we used laser capture microdissection to separate the trophoblast layer from the rest of the placental tissues. RESULTS: A number of genes were differentially expressed in the trophoblast layer when the labor and non-labor groups were compared. The expression of SIRT1, KAP1, and CRH was significantly lower in the trophoblast layer of the labor group than of the non-labor group. The expression of IL-1b, NF-kB1 and TLR 8 in the labor group was significantly higher than that in the non-labor group. CONCLUSIONS: Human term labor may be closely associated with inflammatory response. We suggest that downregulation of SIRT1, KAP1, and CRH gene expression in the trophoblast may play a key role in parturition and initiation of labor in pregnant human females.

  2. Review: Human trophoblast fusion and differentiation: lessons from trisomy 21 placenta.

    Science.gov (United States)

    Pidoux, G; Gerbaud, P; Cocquebert, M; Segond, N; Badet, J; Fournier, T; Guibourdenche, J; Evain-Brion, D

    2012-02-01

    The syncytiotrophoblast layer plays a major role throughout pregnancy, since it is the site of numerous placental functions, including ion and nutrient exchange and the synthesis of steroid and peptide hormones required for fetal growth and development. Inadequate formation and regeneration of this tissue contributes to several pathologies of pregnancy such as intrauterine growth restriction and preeclampsia, which may lead to iatrogenic preterm delivery in order to prevent fetal death and maternal complications. Syncytiotrophoblast formation can be reproduced in vitro using different models. For the last ten years we have routinely purified villous cytotrophoblastic cells (CT) from normal first, second and third trimester placentas and from gestational age-matched Trisomy 21 placentas. We cultured villous CT on plastic dishes to follow the molecular and biochemical aspects of their morphological and functional differentiation. Taking advantage of this unique collection of samples, we here discuss the concept that trophoblast fusion and functional differentiation may be two differentially regulated processes, which are linked but quite distinct. We highlight the major role of mesenchymal-trophoblast cross talk in regulating trophoblast cell fusion. We suggest that the oxidative status of the trophoblast may regulate glycosylation of proteins, including hCG, and thereby modulate major trophoblast cell functions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Expression of Nestin in Embryonic Tissues and its Effects on Clinicopathological Characteristics of Patients with Placenta Previa.

    Science.gov (United States)

    Qiao, Yan-Yan; Chu, Ping

    2017-08-18

    In this study, we examined expression of nestin in the spinal cord, lung, kidney, stomach, colon and intestine tissues at different stages of embryos in patients with placenta previa. Fetuses of 75 patients with placenta previa were assigned to case group and 80 fetuses from healthy pregnant women with normal placenta who voluntarily terminated pregnancy to control group. Clinical data of pregnant women were collected at the time of admission. Blood from elbow vein was collected to determine expression of serum nestin. Tissues from spinal cord, lung, kidney, stomach, colon and intestine in 3-7 months fetuses of the two groups were extracted. Expression of nestin in tissues was detected by immunohistochemistry, western blotting and RT-qPCR. The mRNA expression of nestin in the case group was increased. Nestin expression was correlated with the gestational age, age of foetus and type of placenta previa in patients with placenta previa. Positive nestin expression was detected in the spinal cord, lung, kidney, stomach, intestine and colon tissues in normal and placenta previa embryo at Stage I. The positive cell density and nestin expression decreased at Stage II, and further decreased at Stage III. The case group had higher nestin mRNA and protein levels throughout human fetal development. Findings of this study suggested that, nestin, as a specific marker of neural precursor cells, was expressed in various tissues of the embryo in patients with placenta previa and nestin expression was lower with increased maturation of the embryo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction.

    Science.gov (United States)

    Acosta, Sandra A; Franzese, Nick; Staples, Meaghan; Weinbren, Nathan L; Babilonia, Monica; Patel, Jason; Merchant, Neil; Simancas, Alejandra Jacotte; Slakter, Adam; Caputo, Mathew; Patel, Milan; Franyuti, Giorgio; Franzblau, Max H; Suarez, Lyanne; Gonzales-Portillo, Chiara; Diamandis, Theo; Shinozuka, Kazutaka; Tajiri, Naoki; Sanberg, Paul R; Kaneko, Yuji; Miller, Leslie W; Borlongan, Cesar V

    2013-07-01

    Cell-based therapy is a promising therapy for myocardial infarction. Endogenous repair of the heart muscle after myocardial infarction is a challenge because adult cardiomyocytes have a limited capacity to proliferate and replace damaged cells. Pre-clinical and clinical evidence has shown that cell based therapy may promote revascularization and replacement of damaged myocytes after myocardial infarction. Adult stem cells can be harvested from different sources including bone marrow, skeletal myoblast, and human umbilical cord blood cells. The use of these cells for the repair of myocardial infarction presents various advantages over other sources of stem cells. Among these are easy harvesting, unlimited differentiation capability, and robust angiogenic potential. In this review, we discuss the milestone findings and the most recent evidence demonstrating the therapeutic efficacy and safety of the transplantation of human umbilical cord blood cells as a stand-alone therapy or in combination with gene therapy, highlighting the importance of optimizing the timing, dose and delivery methods, and a better understanding of the mechanisms of action that will guide the clinical entry of this innovative treatment for ischemic disorders, specifically myocardial infarction.

  5. Effect of exercise training on eNOS expression, NO production and oxygen metabolism in human placenta.

    Directory of Open Access Journals (Sweden)

    Robinson Ramírez-Vélez

    Full Text Available OBJECTIVE: To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS, nitric oxide (NO production and oxygen metabolism in human placenta. METHODS: The study included 20 nulliparous in gestational week 16-20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10 took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55-75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each using barbells (1-3 kg/exercise and low-to-medium resistance bands. The control group (n = 10 undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. RESULTS: Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05. Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05. CONCLUSION: Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of exercise on

  6. Placenta abruption - definition

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2014:chap 178. Hull AD, Resnik R. Placenta previa, placenta accreta, abruptio placentae, and ... R, Iams JD, et al, eds. Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. 7th ed. ...

  7. Assessment of three classes of DNA adducts in human placentas from smoking and non-snoking women in the Czech Republic

    Science.gov (United States)

    Three classes of DNA damage were assessed in human placentas collected (2000-2004) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon ...

  8. Uric acid promotes neuronal differentiation of human placenta-derived mesenchymal stem cells in a time- and concentration-dependent manner

    Institute of Scientific and Technical Information of China (English)

    Nailong Yang; Lili Xu; Peng Lin; Jing Cui

    2012-01-01

    Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time- and concentration-dependent manner.

  9. Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors

    Directory of Open Access Journals (Sweden)

    Craig Jeffrey M

    2011-10-01

    Full Text Available Abstract Background The human placenta facilitates the exchange of nutrients, gas and waste between the fetal and maternal circulations. It also protects the fetus from the maternal immune response. Due to its role at the feto-maternal interface, the placenta is subject to many environmental exposures that can potentially alter its epigenetic profile. Previous studies have reported gene expression differences in placenta over gestation, as well as inter-individual variation in expression of some genes. However, the factors contributing to this variation in gene expression remain poorly understood. Results In this study, we performed a genome-wide DNA methylation analysis of gene promoters in placenta tissue from three pregnancy trimesters. We identified large-scale differences in DNA methylation levels between first, second and third trimesters, with an overall progressive increase in average methylation from first to third trimester. The most differentially methylated genes included many immune regulators, reflecting the change in placental immuno-modulation as pregnancy progresses. We also detected increased inter-individual variation in the third trimester relative to first and second, supporting an accumulation of environmentally induced (or stochastic changes in DNA methylation pattern. These highly variable genes were enriched for those involved in amino acid and other metabolic pathways, potentially reflecting the adaptation of the human placenta to different environments. Conclusions The identification of cellular pathways subject to drift in response to environmental influences provide a basis for future studies examining the role of specific environmental factors on DNA methylation pattern and placenta-associated adverse pregnancy outcomes.

  10. Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta

    Science.gov (United States)

    Zhao, Yan; Chen, Jiao; Wang, Xiu; Song, Qi; Xu, Hui-Hui; Zhang, Yun-Hui

    2016-09-01

    Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.

  11. Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta

    Science.gov (United States)

    Zhao, Yan; Chen, Jiao; Wang, Xiu; Song, Qi; Xu, Hui-Hui; Zhang, Yun-Hui

    2016-01-01

    Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth. PMID:27653773

  12. Purification of a Factor from Human Placenta That Stimulates Capillary Endothelial Cell Protease Production, DNA Synthesis, and Migration

    Science.gov (United States)

    Moscatelli, David; Presta, Marco; Rifkin, Daniel B.

    1986-04-01

    A protein that stimulates the production of plasminogen activator and latent collagenase in cultured bovine capillary endothelial cells has been purified 106-fold from term human placenta by using a combination of heparin affinity chromatography, ion-exchange chromatography, and gel chromatography. The purified molecule has a molecular weight of 18,700 as determined by NaDodSO4/PAGE under both reducing and nonreducing conditions. The purified molecule stimulates the production of plasminogen activator and latent collagenase in a dose-dependent manner between 0.1 and 10 ng of protein/ml. The purified protein also stimulates DNA synthesis and chemotaxis in capillary endothelial cells in the same concentration range. Thus, this molecule has all of the properties predicted for an angiogenic factor.

  13. Concentrations of persistent organochlorine compounds in human milk and placenta are higher in Denmark than in Finland

    DEFF Research Database (Denmark)

    Shen, H.; Main, K.M.; Andersson, A.M.

    2008-01-01

    in human milk samples from Finland (n = 65) and Denmark (n = 65) and in placentas from Finland (n = 112) and Denmark (n = 168). RESULTS: 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDE) was the dominant pollutant. beta-Hexa-chloro-cyclohexane (beta-HCH), hexachlorobenzene (HCB), endosulfan-I, dieldrin......, oxychlordane (OXC), cis-heptachloroepoxide (c-HE) and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) were the other main organochlorines detected. Danish samples had significantly higher concentrations of p,p'-DDE, p,p'-DDT, beta-HCH, HCB, dieldrin, c-HE and OXC than did the Finnish samples. Levels...

  14. Expression of Resistin Protein in Normal Human Subcutaneous Adipose Tissue and Pregnant Women Subcutaneous Adipose Tissue and Placenta

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yongming; GUO Tiecheng; ZHANG Muxun; GUO Wei; YU Meixia; XUE Keying; HUANG Shiang; CHEN Yanhong; ZHU Huanli; XU Lijun

    2006-01-01

    The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method.Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905±8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 ± 3818, P < 0.01), non-pregnant women abdomen (38 288±2084, P<0.01), normal human abdomen (39 421±6087, P<0.01)and thigh (14 942 ±6706, P<0. 001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P<0. 001). Pearson analysis revealed that resistin protein was correlated with BMI (r=0.42), fasting insulin concentration (r=0.38),IRI (r=0. 34), BF % (r=0.43) and fasting glucose (r=0. 39), but not with blood pressure,CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher

  15. Bisphenol A Alters β-hCG and MIF Release by Human Placenta: An In Vitro Study to Understand the Role of Endometrial Cells

    Directory of Open Access Journals (Sweden)

    C. Mannelli

    2014-01-01

    Full Text Available A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA. As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2 was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%. After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG and cytokine Macrophage Migration Inhibitory Factor (MIF. The results showed that direct exposure to BPA stimulated the release of both MIF and β-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

  16. Placenta accreta with placenta previa. Case report

    National Research Council Canada - National Science Library

    Hernández-Ojeda, Humberto; Torres-Hernández, Rosa María; Rivera-Hernández, Jorge Onasis

    2014-01-01

    The placenta praevia and acretism placental were concurrently and are conditions of abnormal placenta, in which the villus sampling invade the myometrium at the site of implantation and is associated...

  17. Comparison of the effect of topical application of human milk and dry cord care on the bacterial colonization of umbilical cord in newborn infants

    Directory of Open Access Journals (Sweden)

    Fatemeh Abbaszadeh

    2014-04-01

    Full Text Available Background: Breast milk contains significant amounts of compounds that act as natural antimicrobial agents. This study was conducted to compare the effect of topical application of human milk and dry cord care on bacterial colonization in the umbilical cord of newborn infants. Methods: This clinical trial study was carried out on 174 infants in Kashan. The newborns were randomized to mother's milk group and dry cord care group from the birth. In group 1, the mother rubbed her own milk on the cord stump every 12 hours from 3 hours after birth to 2 days after the umbilical cord separation. In group 2, the mother was recommended not to use any material on the cord. Then, the cord samples were taken four times; 3hours after birth, at days 3 and 7, and 2 days after the umbilical cord separation. Results: The findings of the culture two days after umbilical cord separation indicated that low percentage of neonates in the breast milk (23.1% and dry cord care (28.8% groups had bacterial colonization. Moreover, no significant difference was found between the two groups in terms of growth of pathogenic organisms and normal flora of the skin (P>0.05. Conclusion: Given the low prevalence of pathogenic microorganisms in the two groups, it seems using breast milk and dry cord care are equally effective methods of taking care of umbilical cord.

  18. Saline obtaining and time standardization of prothrombin using thromboplastin of human placenta. Obtención salina y estandarización del tiempo de protrombina utilizando tromboplastina de placenta humana.

    Directory of Open Access Journals (Sweden)

    Deysi González Sarría

    Full Text Available Background: Determining prothombine ‘s time is an important lab test in the study of coagulation disorders. To develop this essay the main reactive was thromboplastin , a substance that is presented in tissue and that has been obtained habitually from the human brain or certain animals but its extraction in labs or its commercial acquisition is difficult at present. Objective: To obtain Thromboplastin throughout the extraction of human placenta and to standardise the determination of pro-time into the obtained reactive Method: Placenta from normal delivery was used from which thromboplastin was obtained using a saline extraction. The reactive was compared with thromboplastin from human brain from ¨Dr. Hermanos Ameijeiras¨ Hospital in Havana City in a group of patients with and without anticoagulant treatment . With the extracted thromplastin similar or compatible results were obtained than with the habitual reactives by using easier and cheaper process.
    Fundamento: La determinación del tiempo de protrombina es un importante examen complementario en el estudio de los trastornos de la coagulación de la sangre. Para la realización del ensayo, se utiliza como reactivo principal tromboplastina, sustancia que se encuentra en varios tejidos y que habitualmente se ha obtenido de cerebro humano o de ciertos animales, pero su extracción en el laboratorio o su adquisición comercial en estos momentos se dificulta. Objetivos: Obtener tromboplastina a través de la extracción salina de placenta humana y estandarizar la determinación del tiempo de protrombina con el reactivo obtenido. Métodos : Se utilizó placenta de partos normales de la cual se obtuvo la tromboplastina utilizando extracción salina. Se comparó el reactivo con una tromboplastina de cerebro humano del Hospital ¨Hermanos Ameijeiras¨ de Ciudad de La Habana

  19. Lotus birth, a holistic approach on physiological cord clamping.

    Science.gov (United States)

    Zinsser, Laura A

    2017-09-04

    The positive effects of delayed cord clamping (DCC) has been extensively researched. DCC means: waiting at least one minute after birth before clamping and cutting the cord or till the pulsation has stopped. With physiological clamping and cutting (PCC) the clamping and cutting can happen at the earliest after the pulsation has stopped. With a Lotus birth, no clamping and cutting of the cord is done. A woman called Clair Lotus Day imitated the holistic approach of PCC from an anthropoid ape in 1974. The chimpanzee did not separate the placenta from the newborn. The aim of this case report is to discuss and learn a different approach in the third stage of labour. Three cases of Lotus birth by human beings were observed. All three women gave birth in an out-of-hospital setting and had ambulant postnatal care. The placenta was washed, salted and herbs were put on 2-3h post partum. The placenta was wrapped in something that absorbs the moisture. The salting was repeated with a degreasing frequency depending on moistness of the placenta. On life day six all three Lotus babies experiences a natural separation of the cord. All three Lotus birth cases were unproblematic, no special incidence occurred. One should differentiate between early cord clamping (ECC), delayed cord clamping (DCC) and physiological cord clamping (PCC). Lotus birth might lead to an optimisation of the bonding and attachment. Research is needed in the areas of both PCC and Lotus birth. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  20. Human Umbilical Cord Blood Cell Transplantation in Neuroregenerative Strategies

    Directory of Open Access Journals (Sweden)

    Luisa R. Galieva

    2017-09-01

    Full Text Available At present there is no effective treatment of pathologies associated with the death of neurons and glial cells which take place as a result of physical trauma or ischemic lesions of the nervous system. Thus, researchers have high hopes for a treatment based on the use of stem cells (SC, which are potentially able to replace dead cells and synthesize neurotrophic factors and other molecules that stimulate neuroregeneration. We are often faced with ethical issues when selecting a source of SC. In addition to precluding these, human umbilical cord blood (hUCB presents a number of advantages when compared with other sources of SC. In this review, we consider the key characteristics of hUCB, the results of various studies focused on the treatment of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, ischemic (stroke and traumatic injuries of the nervous system and the molecular mechanisms of hUCB-derived mononuclear and stem cells.

  1. Generation of induced pluripotent stem cells from human cord blood.

    Science.gov (United States)

    Haase, Alexandra; Olmer, Ruth; Schwanke, Kristin; Wunderlich, Stephanie; Merkert, Sylvia; Hess, Christian; Zweigerdt, Robert; Gruh, Ina; Meyer, Johann; Wagner, Stefan; Maier, Lars S; Han, Dong Wook; Glage, Silke; Miller, Konstantin; Fischer, Philipp; Schöler, Hans R; Martin, Ulrich

    2009-10-02

    Induced pluripotent stem cells (iPSCs) may represent an ideal cell source for future regenerative therapies. A critical issue concerning the clinical use of patient-specific iPSCs is the accumulation of mutations in somatic (stem) cells over an organism's lifetime. Acquired somatic mutations are passed onto iPSCs during reprogramming and may be associated with loss of cellular functions and cancer formation. Here we report the generation of human iPSCs from cord blood (CB) as a juvenescent cell source. CBiPSCs show characteristics typical of embryonic stem cells and can be differentiated into derivatives of all three germ layers, including functional cardiomyocytes. For future therapeutic production of autologous and allogeneic iPSC derivatives, CB could be routinely harvested for public and commercial CB banks without any donor risk. CB could readily become available for pediatric patients and, in particular, for newborns with genetic diseases or congenital malformations.

  2. Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

    Science.gov (United States)

    Emgård, Mia; Piao, Jinghua; Aineskog, Helena; Liu, Jia; Calzarossa, Cinzia; Odeberg, Jenny; Holmberg, Lena; Samuelsson, Eva-Britt; Bezubik, Bartosz; Vincent, Per Henrik; Falci, Scott P; Seiger, Åke; Åkesson, Elisabet; Sundström, Erik

    2014-03-01

    To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

  3. Development of Some Organs Derived from the Three Embryonic Germ Layer in a Degus Ectopic Pregnancy and Presence of a Cytotrophoblast That Mimics Human Chorionic Placenta

    Directory of Open Access Journals (Sweden)

    C. Bosco

    2014-01-01

    Full Text Available This report describes a case of abdominal pregnancy in an adult female degu from which we recovered two large tissular masses from the peritoneal cavity. The bigger one showed a number of thin vascular connections to the serosa layer of the small intestine. It was also directly connected to the smaller mass by a thin membranous process. The surface of the bigger mass facing the small intestine wall showed the presence of chorionic villous that resembled a villous human chorionic placenta, rather than the hemomonochorial labyrinthine placenta, characteristic of this species. This unusual finding leads us to postulate that in the degu’s uterus the cytotrophoblast is exposed to a number of factors that will activate cascades of cellular and molecular events that ultimately will be signaling the cytotrophoblast to develop into a labyrinthine hemomonochorial placenta. In absence of the proper uterine environment, as is the case of the abdominal pregnancy in the peritoneal cavity reported here, the lack of signaling will lead the cytotrophoblast to develop into a villous chorionic placenta, similar to that observed in human.

  4. Profiling gene expression in human placentae of different gestational ages: an OPRU Network and UW SCOR Study.

    Science.gov (United States)

    Mikheev, Andrei M; Nabekura, Tomohiro; Kaddoumi, Amal; Bammler, Theo K; Govindarajan, Rajgopal; Hebert, Mary F; Unadkat, Jashvant D

    2008-11-01

    We used the whole-genome approach to identify major functional categories of genes whose expression depends on gestational age. Using microarray analysis, we compared gene expression profiles in the villous tissues of first (45-59 days) and second trimester (109-115 days) placentae with C-section term placentae. We found that in first trimester placentae, genes related to cell cycle, DNA, amino acids, and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were underrepresented. Among genes involved in organism defense, we identified genes involved in chemical response, metabolism, and transport. Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was changed with gestational age leading to inhibition of beta-catenin protein expression. Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and to compare with gene expression in placentae from complicated pregnancies.

  5. Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

    DEFF Research Database (Denmark)

    Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène;

    2010-01-01

    Human cytomegalovirus (HCMV) contributes to pathogenic processes in immuno-suppressed individuals, in fetuses and in neonates. In the present report by using reporter gene activation assays and confocal microscopy in the presence of specific antagonist we show for the first time that HCMV infection...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness......, as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...

  6. Umbilical cord and preeclampsia.

    Science.gov (United States)

    Olaya-C, M; Salcedo-Betancourt, J; Galvis, S H; Ortiz, A M; Gutierrez, S; Bernal, J E

    2016-01-01

    Preeclampsia is associated with abnormalities in the umbilical cord in several ways: morphological, biochemical and functional. Alteration in blood vessels of the placenta, decidua and circulatory system of the fetus might be related to factors that cause preeclampsia and may be associated with alterations of the umbilical cord. This study aimed to analyze the relationship between each type of umbilical cord abnormality and the different subtypes of hypertensive gestational disorders. We conducted a prospective study on consecutive autopsies and its placentas, looking for abnormalities in the umbilical cord's features and their clinical associations. Umbilical cord abnormalities including length, diameter, insertion, entanglements, knots and coils were associated with maternal gestational hypertension. In women with gestational hypertension, umbilical cord abnormalities are associated with fetal and neonatal consequences.

  7. Expression of adrenomedullin in rats after spinal cord injury and intervention effect of recombinant human erythropoietin

    Science.gov (United States)

    Zhao, Liang; Jing, Yu; Qu, Lin; Meng, Xiangwei; Cao, Yang; Tan, Huibing

    2016-01-01

    The expression of adrenomedullin (ADM) in injured tissue of rat spinal cord was observed and the effect of recombinant human erythropoietin was analyzed. A total of 45 Sprague-Dawley rats were selected and divided into 3 equal groups including, a sham-operation group in which rats received an excision of vertebral plate; a spinal cord injury model group and a recombinant human erythropoietin group in which rats with spinal cord injury received a caudal vein injection of 300 units recombinant human erythropoietin after injury. Hematoxylin and eosin staining was performed to observe the spinal cord injury conditions. Immunohistochemical staining was performed to observe the expression of ADM. Pathologic changes in the group of recombinant human erythropoietin at various times were significantly less severe than those in the group of spinal cord injury model. The expression of ADM was increased particularly in the group of recombinant human erythropoietin (P<0.01). The improved Tarlov scores of the group of spinal cord injury model and the group of recombinant human erythropoietin were lower than those of the sham-operation group at 3, 6 and 9 days (P<0.01). Thus, the recombinant human erythropoietin is capable of alleviating the secondary injury of spinal cord. One of the mechanisms may be achieved by promoting the increase of ADM expression. PMID:28101163

  8. Differential Expression of Collectins in Human Placenta and Role in Inflammation during Spontaneous Labor

    Science.gov (United States)

    Yadav, Ajit Kumar; Chaudhari, Hemangi; Warke, Himangi; Shah, Premanand Keshavlal; Dodagatta-Marri, Eswari; Kishore, Uday; Madan, Taruna

    2014-01-01

    Collectins, collagen-containing Ca2+ dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥37 weeks of gestation), undergoing either elective C-section with no labor (‘NLc’ group, n = 5), or normal vaginal delivery with spontaneous labor (‘SLv’ group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The ‘SLv’ group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the ‘NLc’ group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (pfeto-maternal tissues. PMID:25303045

  9. Changes in the levels of lipoperoxide and antioxidant factors in human placenta during gestation.

    Directory of Open Access Journals (Sweden)

    Takehara,Yoshiki

    1990-04-01

    Full Text Available The concentration of lipoperoxides in maternal blood increases as gestation progresses. The concentration in pregnant women at 40 weeks gestation is 1.6 times higher than in nonpregnant women. The concentration in the cord blood, however, is 70% lower than that in maternal blood. To study the role of placental tissue in the difference in the lipoperoxide concentration between the cord blood and maternal blood, we investigated the lipoperoxide concentration, antioxidant activities and in vitro lipoperoxide formation in placental tissue during pregnancy. The lipoperoxide concentration was 50% lower in placental tissue of 40 weeks gestation than in tissue of 5-11 weeks gestation. Catalase and superoxide dismutase activities in placental tissues increased as gestation progressed, while glutathione peroxidase activity and alpha-tocopherol concentration did not change significantly during the gestational period. The in vitro formation of lipoperoxides in placental tissue decreased as gestation progressed. These results show that placental tissue suppresses lipoperoxide formation in the late gestational age, lowers the concentration of lipoperoxides in the blood and protects the fetus against oxygen toxicity.

  10. Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

    Institute of Scientific and Technical Information of China (English)

    Liqing Yao; Chuan He; Ying Zhao; Jirong Wang; Mei Tang; Jun Li; Ying Wu; Lijuan Ao; Xiang Hu

    2013-01-01

    Stem cell transplantation can promote functional restoration following acute spinal cord injury (injury time 6 months) were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury.

  11. Differential expression of collectins in human placenta and role in inflammation during spontaneous labor.

    Science.gov (United States)

    Yadav, Ajit Kumar; Chaudhari, Hemangi; Warke, Himangi; Shah, Premanand Keshavlal; Dodagatta-Marri, Eswari; Kishore, Uday; Madan, Taruna

    2014-01-01

    Collectins, collagen-containing Ca(2+) dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥ 37 weeks of gestation), undergoing either elective C-section with no labor ('NLc' group, n = 5), or normal vaginal delivery with spontaneous labor ('SLv' group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The 'SLv' group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the 'NLc' group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (pLabor associated cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α and MCP-1 showed significant increase (plabor and SP-D plausibly contributes to the pro-inflammatory immune milieu of feto-maternal tissues.

  12. Optimal transport and the placenta

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, Simon [Los Alamos National Laboratory; Xia, Qinglan [NON LANL; Salafia, Carolym [NON LANL

    2010-01-01

    The goal of this paper is to investigate the expected effects of (i) placental size, (ii) placental shape and (iii) the position of insertion of the umbilical cord on the work done by the foetus heart in pumping blood across the placenta. We use optimal transport theory and modeling to quantify the expected effects of these factors . Total transport cost and the shape factor contribution to cost are given by the optimal transport model. Total placental transport cost is highly correlated with birth weight, placenta weight, FPR and the metabolic scaling factor beta. The shape factor is also highly correlated with birth weight, and after adjustment for placental weight, is highly correlated with the metabolic scaling factor beta.

  13. Statistical Mechanics of the Human Placenta: A Stationary State of a Near-Equilibrium System in a Linear Regime.

    Science.gov (United States)

    Lecarpentier, Yves; Claes, Victor; Hébert, Jean-Louis; Krokidis, Xénophon; Blanc, François-Xavier; Michel, Francine; Timbely, Oumar

    2015-01-01

    All near-equilibrium systems under linear regime evolve to stationary states in which there is constant entropy production rate. In an open chemical system that exchanges matter and energy with the exterior, we can identify both the energy and entropy flows associated with the exchange of matter and energy. This can be achieved by applying statistical mechanics (SM), which links the microscopic properties of a system to its bulk properties. In the case of contractile tissues such as human placenta, Huxley's equations offer a phenomenological formalism for applying SM. SM was investigated in human placental stem villi (PSV) (n = 40). PSV were stimulated by means of KCl exposure (n = 20) and tetanic electrical stimulation (n = 20). This made it possible to determine statistical entropy (S), internal energy (E), affinity (A), thermodynamic force (A / T) (T: temperature), thermodynamic flow (v) and entropy production rate (A / T x v). We found that PSV operated near equilibrium, i.e., A ≺≺ 2500 J/mol and in a stationary linear regime, i.e., (A / T) varied linearly with v. As v was dramatically low, entropy production rate which quantified irreversibility of chemical processes appeared to be the lowest ever observed in any contractile system.

  14. Investigation of human cervical and upper thoracic spinal cord motion: implications for imaging spinal cord structure and function.

    Science.gov (United States)

    Figley, C R; Stroman, P W

    2007-07-01

    Spinal cord (SC) motion is thought to be the dominant source of error in current diffusion and spinal functional MRI (fMRI) methods. However, until now, such motion has not been well characterized in three dimensions. While previous studies have predominantly examined motion in the superior/inferior (S/I) direction, the foci of the present study were the anterior/posterior (A/P) and right/left (R/L) components of human cervical and upper thoracic SC motion. Cardiac-gated, turbofast low-angle shot (turbo-FLASH) cinematic MRI was employed at 3T to acquire images of the cord at 24 phases throughout the cardiac cycle. Time-dependent signal fluctuations within voxels adjacent to the cord/cerebrospinal fluid (CSF) interface were then used to measure SC motion, which was found to occur predictably as a function of cardiac activity. Cord movement was largest in the A/P direction, for which principal components of motion were calculated, thereby indicating consistent patterns of SC oscillation that can potentially be used to improve SC imaging.

  15. Determination of parabens and benzophenone-type UV filters in human placenta. First description of the existence of benzyl paraben and benzophenone-4.

    Science.gov (United States)

    Valle-Sistac, Jennifer; Molins-Delgado, Daniel; Díaz, Marta; Ibáñez, Lourdes; Barceló, Damià; Silvia Díaz-Cruz, M

    2016-03-01

    UV filters and parabens (PBs) are chemicals used in daily personal care and hygiene products to protect materials and humans from the adverse effects of UV radiation and to preserve the integrity of the formulation, respectively. Several studies highlight their widespread environmental occurrence and endocrine disrupting effects. However, little is known about human exposure to these compounds. The objective of this study was to investigate the exposure of human embryos and foetuses to endocrine disrupting UV filters and PBs. Placentas from volunteer mothers in Barcelona were collected at delivery after informed, written consent by the pregnant women. UV filters and parabens were analysed by liquid chromatography-tandem mass spectrometry. The excellent performance of the method allowed measuring the target compounds in human placental tissue at low ng/g fresh weight level. The detection frequency of the selected compounds was in the range 17-100%. Benzophenone-1, methyl paraben, butyl paraben and benzyl paraben were detected in all samples. The highest measured concentration corresponded to methyl paraben, 11.77ng/g fresh weight. Reported concentrations of benzophenone-4 and benzyl paraben constitute the first evidence about their accumulation in placenta. The results obtained corroborate that foetuses are exposed to a wide diversity of UV filters and PBs via the placenta. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Assessment of essential and nonessential metals and different metal exposure biomarkers in the human placenta in a population from the south of Portugal.

    Science.gov (United States)

    Serafim, A; Company, R; Lopes, B; Rosa, J; Cavaco, A; Castela, G; Castela, E; Olea, N; Bebianno, M J

    2012-01-01

    The general population is exposed to metals as trace amounts of metallic compounds are present in air, water, and food. Information on background exposures and biomarker concentrations of environmental chemicals in the general Portuguese population is limited. Therefore, the purpose of this study was to determine the levels of important nonessential metals with recognized toxicity cadmium (Cd) and lead (Pb) and essential metals copper (Cu), nickel (Ni), chromium (Cr), and zinc (Zn) in placentas of mothers living in south Portugal (Algarve). Due to the difficulty in establishing the effects of chemicals in a complex and variable environment, this study also aimed to examine the response of biomarkers, such as biochemical changes that occurs at subcellular levels in the presence of contaminants. The investigated biomarkers in placentas indicative of metal exposure or damage included the metallothioneins (MT), delta-aminolevulinic acid dehydratase (ALAD) (specific for Pb), and lipid peroxidation (LPO) as an index of oxidative stress damage. Moreover, HJ-BIPLOT was applied in order to identify and categorize mothers vulnerable to environmental contamination in this region. Metal concentrations in the placenta were not excessive but within the range found in most European studies. In general, the biomarkers MT and LPO were positively correlated with metal levels, while with ALAD the opposite occurred, indicating the selected battery of biomarkers were suitable to study the effects of metals on human placenta. Further, the application of multivariate analysis with HJ-BIPLOT showed that most significant factors contributing to maternal and fetal exposures via placenta were dietary and smoking habits.

  17. A histopathological analysis of the human cervical spinal cord in patients with acute traumatic central cord syndrome.

    Science.gov (United States)

    Jimenez, O; Marcillo, A; Levi, A D

    2000-09-01

    We have applied conventional histochemical and morphometric techniques to study the changes within the human spinal 'hand' motor neuron pool after spinal cord injury in patients who presented with acute traumatic central cord syndrome (ATCCS). To determine whether a reduction of large alpha motor neurons at the C7, C8 and T1 spinal cord levels underlies the mechanism which causes hand dysfunction seen in patients with (ATCCS). The etiology of upper extremity weakness in ATCCS is debated and injury and/or degeneration of motor neurons within the central gray matter of the cervical enlargement has been advanced as one potential etiology of hand weakness. The spinal cords of five individuals with documented clinical evidence of ATCCS and three age-matched controls were obtained. The ATCCS spinal cords were divided into acute/sub-acute (two cases) and chronic (three cases) groups depending on the time to death after their injury; the chronic group was further subdivided according to the epicenter of injury. We counted the motor neurons using light microscopy in 10 randomly selected axial sections at the C7, C8 and T1 spinal cord levels for each group. We also analyzed the lateral and ventral corticospinal tracts (CST) in all groups for evidence of Wallerian degeneration and compared them to controls. A primary injury to the lateral CST was present in each case of ATCCS with evidence of Wallerian degeneration distal to the epicenter of injury. There was minimal Wallerian degeneration within the ventral corticospinal tracts. In the chronic low cervical injury group, there was a decrease in motor neurons supplying hand musculature relative to the other injury groups where the motor neurons sampled at the time of death were not reduced in number when compared to the control group. We hypothesize that hand dysfunction in ATCCS can be observed after spinal cord injury without any apparent loss in the number of motor neurons supplying the hand musculature as seen in our acute

  18. [Placenta accreta with placenta previa. Case report].

    Science.gov (United States)

    Hernández-Ojeda, Humberto; Torres-Hernández, Rosa María; Rivera-Hernández, Jorge Onasis

    2014-08-01

    The placenta praevia and acretism placental were concurrently and are conditions of abnormal placenta, in which the villus sampling invade the myometrium at the site of implantation and is associated with the partial or complete absence of the decidua. Clinical case: Patient's 32 years of age, with 34 weeks pregnancy. Obstetric history of previous cesarean section, transvaginal bleeding several times; the diagnosis by ultrasound showed placenta praevia occlusive. Surgical treatment was abdominal total hysterectomy.

  19. BOLD MRI of the human cervical spinal cord at 3 tesla.

    Science.gov (United States)

    Stroman, P W; Nance, P W; Ryner, L N

    1999-09-01

    The feasibility of functional MRI of the spinal cord was investigated by carrying out blood oxygen-level dependent (BOLD) imaging of the human cervical spinal cord at a field of 3 T. BOLD imaging of the cervical spinal cord showed an average intensity increase of 7.0% during repeated exercise with the dominant hand with a return to baseline during rest periods. The areas of activation were predominantly on the same side of the spinal cord as the hand performing the exercise, between the levels of the sixth cervical and first thoracic spinal cord segments. The direct correspondence between these areas and those involved with the transmission of motor impulses to the hand, and reception of sensory information from the hand, demonstrates that spinal functional magnetic resonance imaging is feasible. Magn Reson Med 42:571-576, 1999. Copyright 1999 Wiley-Liss, Inc.

  20. Transcutaneous electrical spinal-cord stimulation in humans

    OpenAIRE

    Gerasimenko, Yury; Gorodnichev, Ruslan; Moshonkina, Tatiana; Sayenko, Dimitry; Gad, Parag; Edgerton, V. Reggie

    2015-01-01

    Locomotor behavior is controlled by specific neural circuits called central pattern generators primarily located at the lumbosacral spinal cord. These locomotor-related neuronal circuits have a high level of automaticity; that is, they can produce a “stepping” movement pattern also seen on electromyography (EMG) in the absence of supraspinal and/or peripheral afferent inputs. These circuits can be modulated by epidural spinal-cord stimulation and/or pharmacological intervention. Such interven...

  1. Omentin-1 Is Decreased in Maternal Plasma, Placenta and Adipose Tissue of Women with Pre-Existing Obesity

    OpenAIRE

    2012-01-01

    OBJECTIVE: The aim of this study was to determine (i) the effect of maternal obesity and gestational diabetes mellitus (GDM) on (i) the circulating levels of omentin-1 in cord and maternal plasma, and (ii) gene expression and release of omentin-1 from human placenta and adipose tissue. The effect of pregnancy on circulating omentin-1 levels was also determined. DESIGN: Omentin-1 levels were measured in maternal and cord plasma from obese and non-obese normal glucose tolerant women (NGT; n = 4...

  2. Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Shirin FARIVAR*

    2015-01-01

    chick embryos. J Exp Zool A Comp Exp Biol 2004 Apr 1;301(4:280-9.Mitchell KE, Weiss ML. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003;21(1:50-60.Marcus AJ, Woodbury D. Fetal stem cells from extra-embryonic tissues: do not discard. J Cell Mol Med 2008 Jun;12(3:730-42. doi: 10.1111/j.1582- 4934.2008.00221.x. Epub 2008 Jan 11.Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Quian H, Zhang X. Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int 2006 Sep;30(9:681-7. Epub 2006 Apr 22.In ‘tAnker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FHJ, Willemze R, Fibbe WE, Kanhai HHH. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003;102(4:1548-49.Magatti M, De Munari S, Vertua E, Gibelli L, Wengler GS, Parolini O. Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 2008 Jan;26(1:182-92. Epub 2007 Sep 27.Kang XQ, Zang WJ, Bao LJ, Li DL, Xu XL, Yu XJ. Differentiating characterization of human umbilical cord blood-derived mesenchymal stem cells in vitro. Cell Biol Int 2006 Jul;30(7:569-75. Epub 2006 Mar 6.Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006 May;24(5:1294-301. Epub 2006 Jan 12.Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005 Nov;33(11:1402-16.Jackson JS, Golding JP, Chapon C, Jones WA, Bhakoo KK: Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study. Stem Cell Res Ther 2010 Jun 15;1(2:17. doi: 10.1186/scrt17.Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative

  3. Distribution of cathepsin L in human umbilical cord tissues.

    Science.gov (United States)

    Gogiel, Tomasz; Wolańska, Małgorzata; Galewska, Zofia; Kinalski, Piotr; Sobolewski, Krzysztof; Romanowicz, Lech

    2017-01-01

    The extracellular matrix components show specific distribution patterns within various structures of the umbilical cord, among which Wharton's jelly is especially collagen-rich tissue. Cathepsin L is a potent cysteine protease engaged in degradation of extracellular matrix proteins, including collagens. We evaluated the activity and expression of cathepsin L, and the inhibitory effect of cysteine protease inhibitors in the umbilical cord arteries, vein and Wharton's jelly. Cathepsin L activity and anti-papain inhibitory effect of cysteine protease inhibitors were quantified in extracts of separated umbilical cord tissues using fluorogenic substrates. The results were calculated per DNA content. The enzyme expression was assessed by Western immunoblotting. The active cathepsin L activity (without activation by pepsin digestion), its percentage in the total activity (after pepsin activation), and the expression of the mature single-chain enzyme were the lowest in the umbilical cord arteries and the highest in Wharton's jelly. The effect of cysteine protease inhibitors showed similar distribution as in the case of the active enzyme, being the highest in Wharton's jelly. Distribution of the activity and expression of mature cathepsin L within the umbilical cord probably results from distinctions in the proenzyme activation process. Differences in the action of cysteine protease inhibitors can partly restrict divergences in the enzyme activity that could reflect its expression alone. Differential enzyme action seems to contribute to tissue-specific collagen turnover within the umbilical cord cells, especially those of Wharton's jelly.

  4. Human laminin isolated in a nearly intact, biologically active form from placenta by limited proteolysis

    DEFF Research Database (Denmark)

    Wewer, U; Albrechtsen, R; Manthorpe, M

    1983-01-01

    , was characterized in detail. This monoclonal antibody reacted with human laminin as shown by several lines of evidence. Immunoprecipitation from metabolically labeled culture media of a human amniotic epithelial cell line with the 4E10 antibody followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis...... revealed polypeptides with Mr similar to those of rat laminin. Immunochromatography of placental extracts obtained by limited pepsin digestion yielded material with main polypeptides at 160 and 130 kilodaltons in sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction. These peptic...

  5. Human Placenta Is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells throughout Development

    NARCIS (Netherlands)

    C. Robin (Catherine); K. Bollerot (Karine); S.C. Mendes (Sandra); E. Haak (Esther); M. Crisan (Mihaela); F. Cerisoli (Francesco); I. Lauw (Ivoune); P. Kaimakis (Polynikis); R.J.J. Jorna (Ruud); M. Vermeulen (Mark); M.H. Kayser (Manfred); R. van der Linden (Reinier); P. Imanirad (Parisa); M.M.A. Verstegen (Monique); H. Nawaz-Yousaf (Humaira); N. Papazian (Natalie); E.A.P. Steegers (Eric); T. Cupedo (Tom); E.A. Dzierzak (Elaine)

    2009-01-01

    textabstractHematopoietic stem cells (HSCs) are responsible for the life-long production of the blood system and are pivotal cells in hematologic transplantation therapies. During mouse and human development, the first HSCs are produced in the aorta-gonad-mesonephros region. Subsequent to this emerg

  6. Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma

    DEFF Research Database (Denmark)

    Mamsen, Linn Salto; Jönsson, Bo A.G.; Lindh, Christian H.

    2017-01-01

    AbstractBackground Perfluoroalkyl substances (PFASs) are bio-accumulative pollutants, and prenatal exposure to PFASs is believed to impact human foetal development and may have long-term adverse health effects later in life. Additionally, maternal cigarette smoking may be associated with PFAS lev...

  7. On the Perplexingly Low Rate of Transport of IgG2 across the Human Placenta

    NARCIS (Netherlands)

    Einarsdottir, Helga K.; Stapleton, Nigel M.; Scherjon, Sicco; Andersen, Jan Terje; Rispens, Theo; van der Schoot, C. Ellen; Vidarsson, Gestur

    2014-01-01

    The neonatal receptor, FcRn, mediates both serum half-life extension as well as active transport of maternal IgG to the fetus during pregnancy. Therefore, transport efficiency and half-life go hand-in-hand. However, while the half-life of the human IgG2 subclass is comparable to IgG1, the placental

  8. Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes.

    Science.gov (United States)

    Alam, S M K; Jasti, S; Kshirsagar, S K; Tannetta, D S; Dragovic, R A; Redman, C W; Sargent, I L; Hodes, H C; Nauser, T L; Fortes, T; Filler, A M; Behan, K; Martin, D R; Fields, T A; Petroff, B K; Petroff, M G

    2017-01-01

    Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes. Trophoblast glycoprotein expression was analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. Regulation of 5T4 in cytotrophoblast cells was examined under either differentiating conditions of epidermal growth factor or under varying oxygen conditions. Microvesicles and exosomes were purified from supernatant of cultured and perfused placentas. Trophoblast glycoprotein expression was prominent at the microvillus surface of syncytiotrophoblast and on the extravillous trophoblast cells, with minimal expression in undifferentiated cytotrophoblasts and normal tissues. Trophoblast glycoprotein expression was elevated in malignant tumors. In cytotrophoblasts, 5T4 was induced by in vitro differentiation, and its messenger RNA (mRNA) was increased under conditions of low oxygen. PE placentas expressed higher 5T4 mRNA than matched control placentas. Trophoblast glycoprotein was prominent within shed placental microvesicles and exosomes. Given the potential functional and known immunological importance of 5T4 in cancer, these studies reveal a class of proteins that may influence placental development and/or sensitize the maternal immune system. In extravillous trophoblasts, 5T4 may function in epithelial-to-mesenchymal transition during placentation. The role of syncytiotrophoblast 5T4 is unknown, but its abundance in shed syncytial vesicles may signify route of sensitization of the maternal immune system.

  9. Effect in vitro of the Phenobarbital on the Activity of the Enzyme Adenosine Triphosphatase (ATPase of Sodium and Potassium Dependent in Human Placenta.

    Directory of Open Access Journals (Sweden)

    María De Jesús Sánchez Bouza

    2007-12-01

    Full Text Available Background: Most of the drugs can pass to the fetus through the placenta, conditioning alterations of the development and fetal growth. Objective: To evaluate the effect in vitro of Phenobarbital on the activity of adenosine triphosphatase of sodium and potassium dependent in human placenta. Method: A study in vitro was carried out, in total homogenizes of placentas coming from 30 mothers that were assisted in the Gynecological and Obstetric Educational Provincial Hospital ¨Mariana Grajales¨, in Santa Clara, during the period March-July 1993. Phenobarbital was administered in concentrations of 0,1 mg/ml, 0,15 mg/ml and 0,2 mg/ml, keeping in mind the therapeutic dose to which was prescribed. The analyzed variables were: enzymatic activity and inhibition type. Results: The enzymatic activity of the adenosine triphosphatase of sodium and potassium dependent, diminished in a significant way, proportionally with the diminishment of the administered concentration of Phenobarbital. The inhibitory effect of the drug also turned out to be dependent of the concentration, presenting a major inhibition as the dose was increased. Conclusion: Phenobarbital produced highly significant decrease in the activity of adenosine triphosphatase of sodium and dependent potassium. This inhibition is of competitive type.

  10. Influence of Spinal Cord Integrity on Gait Control in Human Spinal Cord Injury.

    Science.gov (United States)

    Awai, Lea; Bolliger, Marc; Ferguson, Adam R; Courtine, Grégoire; Curt, Armin

    2016-07-01

    Background Clinical trials in spinal cord injury (SCI) primarily rely on simplified outcome metrics (ie, speed, distance) to obtain a global surrogate for the complex alterations of gait control. However, these assessments lack sufficient sensitivity to identify specific patterns of underlying impairment and to target more specific treatment interventions. Objective To disentangle the differential control of gait patterns following SCI beyond measures of time and distance. Methods The gait of 22 individuals with motor-incomplete SCI and 21 healthy controls was assessed using a high-resolution 3-dimensional motion tracking system and complemented by clinical and electrophysiological evaluations applying unbiased multivariate analysis. Results Motor-incomplete SCI patients showed varying degrees of spinal cord integrity (spinal conductivity) with severe limitations in walking speed and altered gait patterns. Principal component (PC) analysis applied on all the collected data uncovered robust coherence between parameters related to walking speed, distortion of intralimb coordination, and spinal cord integrity, explaining 45% of outcome variance (PC 1). Distinct from the first PC, the modulation of gait-cycle variables (step length, gait-cycle phases, cadence; PC 2) remained normal with respect to regained walking speed, whereas hip and knee ranges of motion were distinctly altered with respect to walking speed (PC 3). Conclusions In motor-incomplete SCI, distinct clusters of discretely controlled gait parameters can be discerned that refine the evaluation of gait impairment beyond outcomes of walking speed and distance. These findings are specifically different from that in other neurological disorders (stroke, Parkinson) and are more discrete at targeting and disentangling the complex effects of interventions to improve walking outcome following motor-incomplete SCI.

  11. Optimized protocol for soluble prokaryotic expression, purification and structural analysis of human placenta specific-1(PLAC1).

    Science.gov (United States)

    Nazari, Mahboobeh; Zarnani, Amir-Hassan; Ghods, Roya; Emamzadeh, Rahman; Najafzadeh, Somayeh; Minai-Tehrani, Arash; Mahmoudian, Jafar; Yousefi, Maryam; Vafaei, Sedigheh; Massahi, Sam; Nejadmoghaddam, Mohammad-Reza

    2017-03-16

    Placenta specific -1 (PLAC1) has been recently introduced as a small membrane-associated protein mainly involved in placental development. Expression of PLAC1 transcript has been documented in almost one hundred cancer cell lines standing for fourteen distinct cancer types. The presence of two disulfide bridges makes difficult to produce functional recombinant PLAC1 in soluble form with high yield. This limitation also complicates the structural studies of PLAC1, which is important for prediction of its physiological roles. To address this issue, we employed an expression matrix consisting of two expression vectors, five different E. coli hosts and five solubilization conditions to optimize production of full and truncated forms of human PLAC1. The recombinant proteins were then characterized using an anti-PLAC1-specific antibody in Western blotting (WB) and enzyme linked immunosorbent assay (ELISA). Structure of full length protein was also investigated using circular dichroism (CD). We demonstrated the combination of Origami™ and pCold expression vector to yield substantial amount of soluble truncated PLAC1 without further need for solubilization step. Full length PLAC1, however, expressed mostly as inclusion bodies with higher yield in Origami™ and Rosetta2. Among solubilization buffers examined, buffer containing Urea 2 M, pH 12 was found to be more effective. Recombinant proteins exhibited excellent reactivity as detected by ELISA and WB. The secondary structure of full length PLAC1 was considered by CD spectroscopy. Taken together, we introduced here a simple, affordable and efficient expression system for soluble PLAC1 production.

  12. Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice.

    Science.gov (United States)

    Chatterjee, Piyali; Chiasson, Valorie L; Pinzur, Lena; Raveh, Shani; Abraham, Eytan; Jones, Kathleen A; Bounds, Kelsey R; Ofir, Racheli; Flaishon, Liat; Chajut, Ayelet; Mitchell, Brett M

    2016-04-01

    Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both Pinflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during pregnancy and have a potential therapeutic role in pre-eclampsia treatment.

  13. The effects of dan-shen root on cardiomyogenic differentiation of human placenta-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kun [Department of Clinical Laboratory, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Li, Shi-zheng, E-mail: ychozon@yahoo.com.cn [Department of General Surgery, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Zhang, Yun-li; Wang, Xue-zhe [Department of Clinical Laboratory, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Conditional medium and dan-shen root were used for cardiomyogenic differentiation. Black-Right-Pointing-Pointer They all could induce hPDMSCs to differentiate into cardiomyocytes. Black-Right-Pointing-Pointer The induction effect of the latter was slightly higher compared to that of the former. Black-Right-Pointing-Pointer Dan-shen root could be a good inducer for cardiomyogenic differentiation. -- Abstract: The aim of this study was to search for a good inducer agent using for cardiomyogenic differentiation of stem cells. Human placenta-derived mesenchymal stem cells (hPDMSCs) were isolated and incubated in enriched medium. Fourth passaged cells were treated with 10 mg/L dan-shen root for 20 days. Morphologic characteristics were analyzed by confocal and electron microscopy. Expression of {alpha}-sarcomeric actin was analyzed by immunohistochemistry. Expression of cardiac troponin-I (TnI) was analyzed by immunohistofluorescence. Atrial natriuretic factor (ANF) and beta-myocin heavy chain ({beta}-MHC) were detected by reverse transcriptase polymerase chain reaction (RT-PCR). hPDMSCs treated with dan-shen root gradually formed a stick-like morphology and connected with adjoining cells. On the 20th day, most of the induced cells stained positive with {alpha}-sarcomeric actin and TnI antibody. ANF and {beta}-MHC were also detected in the induced cells. Approximately 80% of the cells were successfully transdifferentiated into cardiomyocytes. In conclusion, dan-shen root is a good inducer agent used for cardiomyogenic differentiation of hPDMSCs.

  14. Observations on the delivered placenta and fetal membranes of the Aardvark, Orycteropus afér (Pallas, 1766)

    NARCIS (Netherlands)

    Taverne, M.A.M.; Bakker-Slotboom, M.F.

    1970-01-01

    A macroscopical description is given of the delivered placenta and foetal membranes of an Aardvark. Special attention is paid to the umbilical cord and the relative position of the foetal membranes at the places where these attach to the placenta. Amniotic pustules were found on the umbilical cord

  15. Human placental multipotent mesenchymal stromal cells modulate placenta angiogenesis through Slit2-Robo signaling.

    Science.gov (United States)

    Chen, Cheng-Yi; Tsai, Chin-Han; Chen, Chia-Yu; Wu, Yi-Hsin; Chen, Chie-Pein

    2016-03-03

    The objective of this study was to investigate whether human placental multipotent mesenchymal stromal cell (hPMSC)-derived Slit2 and endothelial cell Roundabout (Robo) receptors are involved in placental angiogenesis. The hPMSC-conditioned medium and human umbilical vein endothelial cells were studied for Slit2 and Robo receptor expression by immunoassay and RT-PCR. The effect of the conditioned medium of hPMSCs with or without Slit2 depletion on endothelial cells was investigated by in vitro angiogenesis using growth factor-reduced Matrigel. hPMSCs express Slit2 and both Robo1 and Robo4 are present in human umbilical vein endothelial cells. Human umbilical vein endothelial cells do not express Robo2 and Robo3. The hPMSC-conditioned medium and Slit2 recombinant protein significantly inhibit the endothelial cell migration, but not by the hPMSC-conditioned medium with Slit2 depletion. The hPMSC-conditioned medium and Slit2 significantly enhance endothelial tube formation with increased cumulated tube length, polygonal network number and vessel branching point number compared to endothelial cells alone. The tube formation is inhibited by the depletion of Slit2 from the conditioned medium, or following the expression of Robo1, Robo4, and both receptor knockdown using small interfering RNA. Furthermore, co-immunoprecipitation reveals Slit2 binds to Robo1 and Robo4. Robo1 interacts and forms a heterodimeric complex with Robo4. These results suggest the implication of both Robo receptors with Slit2 signaling, which is involved in endothelial cell angiogenesis. Slit2 in the conditioned medium of hPMSCs has functional effect on endothelial cells and may play a role in placental angiogenesis.

  16. Placenta percreta: methotrexate treatment and MRI findings.

    Science.gov (United States)

    Heiskanen, Nonna; Kröger, Jaana; Kainulainen, Sakari; Heinonen, Seppo

    2008-02-01

    Our patient was a 24-year-old gravida 2 para 0 woman. After delivery, placenta percreta was noticed. There was no postpartum hemorrhage, and the patient desired future pregnancies. Although placenta percreta is rare, its sequelae include potentially lethal hemorrhage and loss of reproduction function. Placenta percreta was confirmed histologically and with ultrasonography and magnetic resonance imaging (MRI). Placenta percreta was treated conservatively with methotrexate. On follow-up, MRI showed a small calcified transmural extension of the placenta throughout the uterus in the right fundal area. Color Doppler ultrasonography showed no blood flow in the corresponding area, and maternal serum human chorionic gonadotropin (hCG) was undetectable. Use of MRI is a new method to detect abnormal placentation, and it could be used on follow-up in selective cases with other follow-up modalities. However, it seems likely that conservative management to preserve future fertility remains a secured and reasonable alternative when a patient has no active bleeding.

  17. A review of oscillating field stimulation to treat human spinal cord injury.

    Science.gov (United States)

    Shapiro, Scott

    2014-01-01

    To report the results of use of a human oscillating field stimulator (OFS) in a phase 1 trial of 14 human patients with complete motor and sensory spinal cord injury. Entry criteria were complete spinal cord injury between C5 and T10 in patients 18-65 years old with no transection on magnetic resonance imaging. All patients received the National Acute Spinal Cord Injury Study III methylprednisolone protocol. Cord compression or instability was treated before entry. All patient injuries remained complete (based on American Spinal Cord Injury scoring) with no somatosensory evoked potentials (SSEPs) below the injury after surgery or for 48 hours. All patients were implanted with the OFS within 18 days. Patients were checked every 2 weeks after implantation. The OFS was explanted at 15 weeks. Independent neurologic examinations (American Spinal Cord Injury score, visual analog scale for pain, and SSEPs) were done at 6 weeks, 6 months, and 1 year. Statistical analyses were done by Wilcoxon rank sum test and analysis of variance (ANOVA). There were no complications at insertion, and one wound infection occurred after explant for a 3.5% infection rate. One patient was lost to follow-up after 6 months. All 14 patients had a mean visual analog scale score of 8 at implant and 2 at 6 months, and 13 remained a mean score of 2 at 1 year. Mean improvement in light touch score at 1 year was 25.9 points (ANOVA, P injuries, six had improvement in arm SSEPs, and one recovered a tibial SSEP. Of six patients with thoracic injuries, one recovered an abnormal lower SSEP. Treatment of human spinal cord injury with an OFS is safe, reliable, and easy. Compared with National Acute Spinal Cord Injury Study III compliant paralyzed patients, our results suggest efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta.

    Science.gov (United States)

    Whidbey, Christopher; Harrell, Maria Isabel; Burnside, Kellie; Ngo, Lisa; Becraft, Alexis K; Iyer, Lakshminarayan M; Aravind, L; Hitti, Jane; Waldorf, Kristina M Adams; Rajagopal, Lakshmi

    2013-06-03

    Microbial infection of the amniotic fluid is a significant cause of fetal injury, preterm birth, and newborn infections. Group B Streptococcus (GBS) is an important human bacterial pathogen associated with preterm birth, fetal injury, and neonatal mortality. Although GBS has been isolated from amniotic fluid of women in preterm labor, mechanisms of in utero infection remain unknown. Previous studies indicated that GBS are unable to invade human amniotic epithelial cells (hAECs), which represent the last barrier to the amniotic cavity and fetus. We show that GBS invades hAECs and strains lacking the hemolysin repressor CovR/S accelerate amniotic barrier failure and penetrate chorioamniotic membranes in a hemolysin-dependent manner. Clinical GBS isolates obtained from women in preterm labor are hyperhemolytic and some are associated with covR/S mutations. We demonstrate for the first time that hemolytic and cytolytic activity of GBS is due to the ornithine rhamnolipid pigment and not due to a pore-forming protein toxin. Our studies emphasize the importance of the hemolytic GBS pigment in ascending infection and fetal injury.

  19. Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications

    Science.gov (United States)

    Lecarpentier, E.; Bhatt, M.; Bertin, G. I.; Deloison, B.; Salomon, L. J.; Deloron, P.; Fournier, T.; Barakat, A. I.; Tsatsaris, V.

    2016-01-01

    Introduction In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. Material and Methods To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. Results The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour. Conclusion Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB. PMID:26815115

  20. Human spinal cord injury : motor unit properties and behaviour

    NARCIS (Netherlands)

    Thomas, C. K.; Bakels, R.; Klein, C. S.; Zijdewind, I.

    2014-01-01

    Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when

  1. Development and aging of human spinal cord circuitries

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Willerslev-Olsen, Maria; Lorentzen, Jakob

    2017-01-01

    development and to what extent they are shaped according to the demands of the body that they control and the environment that the body has to interact with. We also discuss how ageing processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries...

  2. Human spinal cord injury : motor unit properties and behaviour

    NARCIS (Netherlands)

    Thomas, C. K.; Bakels, R.; Klein, C. S.; Zijdewind, I.

    Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when

  3. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid.

    Science.gov (United States)

    Collado, Maria Carmen; Rautava, Samuli; Aakko, Juhani; Isolauri, Erika; Salminen, Seppo

    2016-03-22

    Interaction with intestinal microbes in infancy has a profound impact on health and disease in later life through programming of immune and metabolic pathways. We collected maternal faeces, placenta, amniotic fluid, colostrum, meconium and infant faeces samples from 15 mother-infant pairs in an effort to rigorously investigate prenatal and neonatal microbial transfer and gut colonisation. To ensure sterile sampling, only deliveries at full term by elective caesarean section were studied. Microbiota composition and activity assessment by conventional bacterial culture, 16S rRNA gene pyrosequencing, quantitative PCR, and denaturing gradient gel electrophoresis revealed that the placenta and amniotic fluid harbour a distinct microbiota characterised by low richness, low diversity and the predominance of Proteobacteria. Shared features between the microbiota detected in the placenta and amniotic fluid and in infant meconium suggest microbial transfer at the foeto-maternal interface. At the age of 3-4 days, the infant gut microbiota composition begins to resemble that detected in colostrum. Based on these data, we propose that the stepwise microbial gut colonisation process may be initiated already prenatally by a distinct microbiota in the placenta and amniotic fluid. The link between the mother and the offspring is continued after birth by microbes present in breast milk.

  4. Nanomaterial interference with early human placenta: Sophisticated matter meets sophisticated tissues.

    Science.gov (United States)

    Juch, Herbert; Nikitina, Liudmila; Debbage, Paul; Dohr, Gottfried; Gauster, Martin

    2013-11-01

    Next to nothing is known about nanoparticle and nanofiber trafficking at the feto-maternal interface in early human pregnancy. As the first trimester is thought to be crucial for the further placental and fetal development, it will be important to assess the possible risks of nanomaterial exposures during this period. There are some intriguing observations in nanotoxicology, however, indicating certain differences between classical toxicology and nanotoxicology. To understand nanomaterial-biokinetics and placental toxicity in early gestation, the special architecture, the hypoxic condition, the bilayer of villous trophoblast, the plugging of spiral arteries and the contribution of intrauterine glands to nutrition, as well as the delicate immunologic situation at the implantation site, will have to be considered. Unless nano-specific biokinetics are properly understood, it will be difficult to ensure identification of potential "nano-thalidomides" among all the newly engineered nanoparticles and fibers, based on the models available in reproductive toxicology. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Mechanism of Trypanosoma cruzi Placenta Invasion and Infection: The Use of Human Chorionic Villi Explants

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    Ricardo E. Fretes

    2012-01-01

    Full Text Available Congenital Chagas disease, a neglected tropical disease, endemic in Latin America, is associated with premature labor and miscarriage. During vertical transmission the parasite Trypanosoma cruzi (T. cruzi crosses the placental barrier. However, the exact mechanism of the placental infection remains unclear. We review the congenital transmission of T. cruzi, particularly the role of possible local placental factors that contribute to the vertical transmission of the parasite. Additionally, we analyze the different methods available for studying the congenital transmission of the parasite. In that context, the ex vivo infection with T. cruzi trypomastigotes of human placental chorionic villi constitutes an excellent tool for studying parasite infection strategies as well as possible local antiparasitic mechanisms.

  6. Placental transfer of enfuvirtide in the ex vivo human placenta perfusion model.

    Science.gov (United States)

    Ceccaldi, Pierre-Francois; Ferreira, Claudia; Gavard, Laurent; Gil, Sophie; Peytavin, Gilles; Mandelbrot, Laurent

    2008-04-01

    The objective of the study was to determine the placental transfer of the antiretroviral fusion inhibitor, enfuvirtide (Fuzeon). Human cotyledons were perfused for 90 minutes in an open dual circuit with enfuvirtide, and fetal venous samples were collected every 5 minutes. Three perfusion experiments were validated using antipyrine. Enfuvirtide was not detected in the fetal compartment in any of the 3 experiments. The mean concentration of the drug measured in the maternal compartment was 12,400 ng/mL (range, 6500-16,200 ng/mL), which is 2.5 times the maximum concentration recommended for patients treated with enfuvirtide. Even at maternal concentrations twice above therapeutic levels, no placental transfer of enfuvirtide was observed. The high molecular weight of the molecule (4492 kDa) and its ionized state may account for the lack of placental transfer. This result suggests that enfuvirtide could be used in HIV-infected pregnant women without causing fetal exposure.

  7. Quantitative analysis of the toxicity of human amniotic fluid to cultured rat spinal cord.

    Science.gov (United States)

    Drewek, M J; Bruner, J P; Whetsell, W O; Tulipan, N

    1997-10-01

    It has been proposed that the myelodysplastic components of a myelomeningocele are secondarily damaged as the result of exposure to amniotic fluid, the so-called 'two-hit' hypothesis. The critical time at which this secondary insult might occur has not been clearly defined. The present study addresses this issue by quantitatively assessing the toxic effects of human amniotic fluid of various gestational ages upon organotypic cultures of rat spinal cord. Using an assay for lactate dehydrogenase efflux to evaluate toxicity in such spinal cord cultures, we found that the amniotic fluid became toxic at approximately 34 weeks' gestation. This toxic effect of amniotic fluid appears to emerge rather suddenly. Accordingly, it seems reasonable to suggest that prevention of exposure of vulnerable spinal cord tissue to this toxicity by surgical closure of a myelomeningocele defect prior to the emergence of toxicity in amniotic fluid may prevent injury to vulnerable myelodysplastic spinal cord tissue.

  8. Transcutaneous electrical spinal-cord stimulation in humans.

    Science.gov (United States)

    Gerasimenko, Yury; Gorodnichev, Ruslan; Moshonkina, Tatiana; Sayenko, Dimitry; Gad, Parag; Reggie Edgerton, V

    2015-09-01

    Locomotor behavior is controlled by specific neural circuits called central pattern generators primarily located at the lumbosacral spinal cord. These locomotor-related neuronal circuits have a high level of automaticity; that is, they can produce a "stepping" movement pattern also seen on electromyography (EMG) in the absence of supraspinal and/or peripheral afferent inputs. These circuits can be modulated by epidural spinal-cord stimulation and/or pharmacological intervention. Such interventions have been used to neuromodulate the neuronal circuits in patients with motor-complete spinal-cord injury (SCI) to facilitate postural and locomotor adjustments and to regain voluntary motor control. Here, we describe a novel non-invasive stimulation strategy of painless transcutaneous electrical enabling motor control (pcEmc) to neuromodulate the physiological state of the spinal cord. The technique can facilitate a stepping performance in non-injured subjects with legs placed in a gravity-neutral position. The stepping movements were induced more effectively with multi-site than single-site spinal-cord stimulation. From these results, a multielectrode surface array technology was developed. Our preliminary data indicate that use of the multielectrode surface array can fine-tune the control of the locomotor behavior. As well, the pcEmc strategy combined with exoskeleton technology is effective for improving motor function in paralyzed patients with SCI. The potential impact of using pcEmc to neuromodulate the spinal circuitry has significant implications for furthering our understanding of the mechanisms controlling locomotion and for rehabilitating sensorimotor function even after severe SCI. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Fusion of Cytothrophoblast with Syncytiotrophoblast in the Human Placenta: Factors Involved in Syncytialization

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    Gauster M

    2008-01-01

    Full Text Available Human placental villi are covered by a characteristic epithelial-like layer. It consists of mononucleated cytotrophoblasts and an overlyingsyncytiotrophoblast layer both in contact to the trophoblastic basement membrane. The syncytiotrophoblast mostly lacks DNA replication andseems to transcribe only barely mRNA. Therefore, the syncytiotrophoblast depends on cell compounds delivered by fusing cytotrophoblasts. Delivery of fresh cytoplasmic contents into the syncytiotrophoblast is achieved by continuous fusion with cytotrophoblasts throughout gesta-tion. Fusion between cytotrophoblasts and the syncytiotrophoblast is driven by multiple factors, including environmental growth factors andcytokines, which turn on a specific cascade of fusogenic proteins in cytotrophoblasts destined for fusion. The cascade includes protein kinasesand transcription factors, as well as induced expression of fusion-promoting proteins associated with the cell membrane. Additionally, specificproteases are activated, which cleave and remodel structural proteins to prepare the cell for fusion. However, not only fusogenic proteins, butalso plasma membrane architecture and physicochemical factors such as calcium and oxygen affect intertrophoblastic fusion. Coordinatedaction of all factors involved is crucial for proper cytotrophoblast – syncytiotrophoblast fusion. Deregulation of a single factor might cause aninadequate fusion rate and could lead to pregnancy complications such as preeclampsia or even spontaneous abortion.

  10. Omentin-1 is decreased in maternal plasma, placenta and adipose tissue of women with pre-existing obesity.

    Directory of Open Access Journals (Sweden)

    Gillian Barker

    Full Text Available OBJECTIVE: The aim of this study was to determine (i the effect of maternal obesity and gestational diabetes mellitus (GDM on (i the circulating levels of omentin-1 in cord and maternal plasma, and (ii gene expression and release of omentin-1 from human placenta and adipose tissue. The effect of pregnancy on circulating omentin-1 levels was also determined. DESIGN: Omentin-1 levels were measured in maternal and cord plasma from obese and non-obese normal glucose tolerant women (NGT; n = 44 and women with GDM (n = 39 at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of omentin-1 was measured from 22 NGT and 22 GDM women collected at the time of term elective Caesarean section. Omentin-1 levels were also measured in maternal plasma from 13 NGT women at 11 and 28 weeks gestation and 7 weeks postpartum. RESULTS: Maternal obesity was associated with significantly lower omentin-1 levels in maternal plasma; however, there was no effect of maternal obesity on cord omentin levels. Omentin-1 gene expression was lower in placenta and adipose tissue obtained from women with pre-existing obesity. In addition to this, adipose tissue release of omentin-1 was significantly lower from obese pregnant women. Omentin-1 levels were significantly lower in non-obese GDM compared to non-obese NGT women. However, there was no difference in omentin-1 levels between obese NGT and obese GDM women. There was no effect of GDM on cord omentin levels, and placental and adipose tissue omentin-1 expression. Maternal omentin-1 levels were negatively correlated with fetal birthweight and fetal ponderal index. CONCLUSIONS: The data presented in this study demonstrate that pre-existing maternal obesity is associated with lower omentin-1 expression in placenta, adipose tissue and maternal plasma. Alteration in omentin-1 in pregnancy may influence the development of metabolic disorders in offspring later in life.

  11. DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta.

    Science.gov (United States)

    Novakovic, Boris; Wong, Nick C; Sibson, Mandy; Ng, Hong-Kiat; Morley, Ruth; Manuelpillai, Ursula; Down, Thomas; Rakyan, Vardhman K; Beck, Stephan; Hiendleder, Stefan; Roberts, Claire T; Craig, Jeffrey M; Saffery, Richard

    2010-03-26

    The genome of extraembryonic tissue, such as the placenta, is hypomethylated relative to that in somatic tissues. However, the origin and role of this hypomethylation remains unclear. The DNA methyltransferases DNMT1, -3A, and -3B are the primary mediators of the establishment and maintenance of DNA methylation in mammals. In this study, we investigated promoter methylation-mediated epigenetic down-regulation of DNMT genes as a potential regulator of global methylation levels in placental tissue. Although DNMT3A and -3B promoters lack methylation in all somatic and extraembryonic tissues tested, we found specific hypermethylation of the maintenance DNA methyltransferase (DNMT1) gene and found hypomethylation of the DNMT3L gene in full term and first trimester placental tissues. Bisulfite DNA sequencing revealed monoallelic methylation of DNMT1, with no evidence of imprinting (parent of origin effect). In vitro reporter experiments confirmed that DNMT1 promoter methylation attenuates transcriptional activity in trophoblast cells. However, global hypomethylation in the absence of DNMT1 down-regulation is apparent in non-primate placentas and in vitro derived human cytotrophoblast stem cells, suggesting that DNMT1 down-regulation is not an absolute requirement for genomic hypomethylation in all instances. These data represent the first demonstration of methylation-mediated regulation of the DNMT1 gene in any system and demonstrate that the unique epigenome of the human placenta includes down-regulation of DNMT1 with concomitant hypomethylation of the DNMT3L gene. This strongly implicates epigenetic regulation of the DNMT gene family in the establishment of the unique epigenetic profile of extraembryonic tissue in humans.

  12. Human Umbilical Cord Mesenchymal Stromal Cells Support Viability of Umbilical Cord Blood Hematopoietic Stem Cells but not the "Stemness" of Their Progeny in Co-Culture.

    Science.gov (United States)

    Romanov, Yu A; Volgina, N E; Balashova, E E; Kabaeva, N V; Dugina, T N; Sukhikh, G T

    2017-08-01

    Cell-cell interactions and the ability of mesenchymal stromal cells to support the expansion of hematopoietic progenitor cells were studied in co-culture of human umbilical cord tissue-derived mesenchymal stromal cells and nucleated umbilical cord blood cells. It was found that hematopoietic stem cells from the umbilical cord blood are capable to adhere to mesenchymal stromal cells and proliferate during 3-4 weeks in co-culture. However, despite the formation of hematopoietic foci and accumulation of CD34(+) and CD133(+) cells in the adherent cell fraction, the ability of newly generated blood cells to form colonies in semi-solid culture medium was appreciably reduced. These findings suggest that human umbilical cord tissue-derived mesenchymal stromal cells display a weak capability to support the "stemness" of hematopoietic stem cell progeny despite long-term maintenance of their viability and proliferation.

  13. Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes.

    Science.gov (United States)

    Lawrence, Jane M; Stroman, Patrick W; Kollias, Spyros S

    2008-03-01

    We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.

  14. Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, Jane M. [University Hospital of Zurich, Institute of Neuroradiology, Zurich (Switzerland); University of Manitoba, Department of Physiology, Winnipeg, Manitoba (Canada); Stroman, Patrick W. [Queen' s University, Department of Diagnostic Radiology, Kingston, Ontario (Canada); Kollias, Spyros S. [University Hospital of Zurich, Institute of Neuroradiology, Zurich (Switzerland)

    2008-03-15

    We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements. (orig.)

  15. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells

    Science.gov (United States)

    Wang, Limin; Ott, Lindsey; Seshareddy, Kiran; Weiss, Mark L; Detamore, Michael S

    2011-01-01

    Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue engineering and regenerative medicine, yet with so many sources of MSCs, what are the primary criteria for selecting leading candidates? Ideally, the cells will be multipotent, inexpensive, lack donor site morbidity, donor materials should be readily available in large numbers, immunocompatible, politically benign and expandable in vitro for several passages. Bone marrow MSCs do not meet all of these criteria and neither do embryonic stem cells. However, a promising new cell source is emerging in tissue engineering that appears to meet these criteria: MSCs derived from Wharton’s jelly of umbilical cord MSCs. Exposed to appropriate conditions, umbilical cord MSCs can differentiate in vitro along several cell lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal, pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have demonstrated in vivo differentiation ability and promising immunocompatibility with host organs/tissues, even in xenotransplantation. In this article, we address their cellular characteristics, multipotent differentiation ability and potential for tissue engineering with an emphasis on musculoskeletal tissue engineering. PMID:21175290

  16. What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Yeung Trevor M

    2011-09-01

    Full Text Available Abstract Background Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway. Discussion The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process. Summary This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.

  17. Characterization of Adherent Nonhematopoietic Cells Derived from Human Umbilical Cord Blood

    Institute of Scientific and Technical Information of China (English)

    安小惠; 蔡国平

    2003-01-01

    To confirm and characterize the adherent fibroblast-like progenitors in human umbilical cord blood, we isolated mononuclear cells from human umbilical cord blood by Ficoll-Hypaque.Two main morphologically different kinds of cells were formed by culturing the cells in collagen-coated 24-well plastic dishes and flasks.One type was the adherent fibroblast-like cells, while the other was loosely adherent clonally expanded round cells.Our experiments demonstrate that the adherent fibroblast-like cells possess multilineage potential, including the ability to differentiate into endothelial-like cells and to express the mesenchymal cell marker.

  18. Potential of human dental stem cells in repairing the complete transection of rat spinal cord

    Science.gov (United States)

    Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

    2017-04-01

    Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

  19. Xeno-free culture condition for human bone marrow and umbilical cord matrix-derived mesenchymal stem/stromal cells using human umbilical cord blood serum

    Science.gov (United States)

    Esmaeli, Azadeh; Moshrefi, Mojgan; Shamsara, Ali; Eftekhar-vaghefi, Seyed Hasan; Nematollahi-mahani, Seyed Noureddin

    2016-01-01

    Background: Fetal bovine serum (FBS) is widely used in cell culture laboratories, risk of zoonotic infections and allergic side effects create obstacles for its use in clinical trials. Therefore, an alternative supplement with proper inherent growth-promoting activities is demanded. Objective: To find FBS substitute, we tested human umbilical cord blood serum (hUCS) for proliferation of human umbilical cord matrix derived mesenchymal stem cells (hUC-MSCs) and human bone marrow-derived mesenchymal cells (hBM-MSCs). Materials and Methods: Umbilical cord blood of healthy neonates, delivered by Caesarian section, was collected and the serum was separated. hUC-MSCs and hBM-MSCs were isolated and characterized by assessment of cell surface antigens by flow cytometry, alkaline phosphatase activity and osteogenic/adipogenic differentiation potential. The cells were then cultured in Iscove's Modified Dulbecco's Medium (IMDM) by conventional methods in three preparations: 1- with hUCS, 2- with FBS, and 3- without serum supplements. Cell proliferation was measured using WST-1 assay, and cell viability was assessed by trypan blue staining. Results: The cells cultured in hUCS and FBS exhibited similar morphology and mesenchymal stem cells properties. WST-1 proliferation assay data showed no significant difference between the proliferation rate of either cells following hUCS and FBS supplementation. Trypan blue exclusion dye test also revealed no significant difference for viability between hUCS and FBS groups. A significant difference was detected between the proliferation rate of stem cells cultured in serum-supplemented medium compared with serum-free medium. Conclusion: Our results indicate that human umbilical cord serum can effectively support proliferation of hBM-MSCS and hUC-MSCs in vitro and can be used as an appropriate substitute for FBS, especially in clinical studies. PMID:27738658

  20. Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus.

    Science.gov (United States)

    Stenqvist, Ann-Christin; Nagaeva, Olga; Baranov, Vladimir; Mincheva-Nilsson, Lucia

    2013-12-01

    Apoptosis is crucially important in mediating immune privilege of the fetus during pregnancy. We investigated the expression and in vitro apoptotic activity of two physiologically relevant death messengers, the TNF family members Fas ligand (FasL) and TRAIL in human early and term placentas. Both molecules were intracellularly expressed, confined to the late endosomal compartment of the syncytiotrophoblast, and tightly associated to the generation and secretion of placental exosomes. Using immunoelectron microscopy, we show that FasL and TRAIL are expressed on the limiting membrane of multivesicular bodies where, by membrane invagination, intraluminal microvesicles carrying membranal bioactive FasL and TRAIL are formed and released in the extracellular space as exosomes. Analyzing exosomes secreted from placental explant cultures, to our knowledge, we demonstrate for the first time that FasL and TRAIL are clustered on the exosomal membrane as oligomerized aggregates ready to form death-inducing signaling complex. Consistently, placental FasL- and TRAIL-carrying exosomes triggered apoptosis in Jurkat T cells and activated PBMC in a dose-dependent manner. Limiting the expression of functional FasL and TRAIL to exosomes comprise a dual benefit: 1) storage of exosomal FasL and TRAIL in multivesicular bodies is protected from proteolytic cleavage and 2) upon secretion, delivery of preformed membranal death molecules by exosomes rapidly triggers apoptosis. Our results suggest that bioactive FasL- and TRAIL-carrying exosomes, able to convey apoptosis, are secreted by the placenta and tie up the immunomodulatory and protective role of human placenta to its exosome-secreting ability.

  1. Review: Toward an integrated evolutionary understanding of the mammalian placenta.

    Science.gov (United States)

    Wildman, D E

    2011-03-01

    The placenta is fundamentally important for the success of pregnancy. Disruptions outside the normal range for placental function can result in pregnancy failure and other complications. The anatomy of the placenta varies greatly across mammals, as do key parameters in pregnancy such as neonatal body mass, length of gestation and number of offspring per pregnancy. An accurate understanding of the evolution of the mammalian placenta will require at minimum the integration of anatomical, developmental, physiological, genetic, and epigenetic data. Currently available data suggest that the placenta is a dynamic organ that has evolved rapidly in a lineage specific manner. Examination of the placenta from the perspective of human evolution shows that many anatomical features of the human placenta are relatively conserved. Despite the anatomical conservation of the human placenta there are many recently evolved placenta-specific genes (e.g. CGB, LGALS13, GH2) that are important in the development and function of the human placenta. Other mammalian genomes have also evolved specific suites of placenta-expressed genes. For example, rodents have undergone expansions of the cathepsin and prolactin families, and artiodactyls have expanded their suite of pregnancy-associated glycoproteins. In addition to lineage specific birth and death of gene family members, the pattern of imprinted loci varies greatly among species. Taken together, these studies suggest that a strategy reliant upon the sampling of placentally expressed and imprinted genes from a phylogenetically diverse range of species is appropriate for unraveling the conserved and derived aspects of placental biology.

  2. The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta.

    Directory of Open Access Journals (Sweden)

    Helena Kaihola

    Full Text Available Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12 and compared them with placenta from depressed (n = 12 and healthy mothers (n = 12. Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the

  3. The astroglial response to Wallerian degeneration after spinal cord injury in humans.

    Science.gov (United States)

    Puckett, W R; Hiester, E D; Norenberg, M D; Marcillo, A E; Bunge, R P

    1997-12-01

    We describe the changes exhibited by astrocytes in areas of Wallerian degeneration after spinal cord injury in humans using glial fibrillary acidic protein immunohistochemistry correlated to standard histology at time points ranging from 8 days to 23 years after injury. Astrocytes were slow to react; a slight increase in immunoreactivity was observed at 4 months. Over time they began to lose immunoreactivity in both the somata and the processes as the debris from the degenerative process was cleared. By 1 year after injury the staining intensity had decreased to levels which were lower than in normal areas of the cord. This hypointense staining persisted for at least 23 years after injury. These findings are significantly different from those observed in animal studies and emphasize the need for additional pathological studies of human spinal cord injury. Copyright 1997 Academic Press.

  4. Early human herpes virus type 6 reactivation in umbilical cord blood allogeneic stem cell transplantation.

    Science.gov (United States)

    Cirrone, Frank; Ippoliti, Cindy; Wang, Hanhan; Zhou, Xi Kathy; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; van Besien, Koen

    2016-11-01

    Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).

  5. A curated transcriptome dataset collection to investigate the development and differentiation of the human placenta and its associated pathologies [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Alexandra K. Marr

    2016-05-01

    Full Text Available Compendia of large-scale datasets made available in public repositories provide a precious opportunity to discover new biomedical phenomena and to fill gaps in our current knowledge. In order to foster novel insights it is necessary to ensure that these data are made readily accessible to research investigators in an interpretable format. Here we make a curated, public, collection of transcriptome datasets relevant to human placenta biology available for further analysis and interpretation via an interactive data browsing interface. We identified and retrieved a total of 24 datasets encompassing 759 transcriptome profiles associated with the development of the human placenta and associated pathologies from the NCBI Gene Expression Omnibus (GEO and present them in a custom web-based application designed for interactive query and visualization of integrated large-scale datasets (http://placentalendocrinology.gxbsidra.org/dm3/landing.gsp. We also performed quality control checks using relevant biological markers. Multiple sample groupings and rank lists were subsequently created to facilitate data query and interpretation. Via this interface, users can create web-links to customized graphical views which may be inserted into manuscripts for further dissemination, or e-mailed to collaborators for discussion. The tool also enables users to browse a single gene across different projects, providing a mechanism for  developing new perspectives on the role of a molecule of interest across multiple biological states. The dataset collection we created here is available at: http://placentalendocrinology.gxbsidra.org/dm3.

  6. Real-Time Tracking of BODIPY-C12 Long-Chain Fatty Acid in Human Term Placenta Reveals Unique Lipid Dynamics in Cytotrophoblast Cells.

    Directory of Open Access Journals (Sweden)

    Kevin Kolahi

    Full Text Available While the human placenta must provide selected long-chain fatty acids to support the developing fetal brain, little is known about the mechanisms underlying the transport process. We tracked the movement of the fluorescently labeled long-chain fatty acid analogue, BODIPY-C12, across the cell layers of living explants of human term placenta. Although all layers took up the fatty acid, rapid esterification of long-chain fatty acids and incorporation into lipid droplets was exclusive to the inner layer cytotrophoblast cells rather than the expected outer syncytiotrophoblast layer. Cytotrophoblast is a progenitor cell layer previously relegated to a repair role. As isolated cytotrophoblasts differentiated into syncytialized cells in culture, they weakened their lipid processing capacity. Syncytializing cells suppress previously active genes that regulate fatty-acid uptake (SLC27A2/FATP2, FABP4, ACSL5 and lipid metabolism (GPAT3, LPCAT3. We speculate that cytotrophoblast performs a previously unrecognized role in regulating placental fatty acid uptake and metabolism.

  7. Role of SOCS3 in the Jak/stat3 pathway in the human placenta: different mechanisms for preterm and term labor.

    Science.gov (United States)

    Zhou, Xin; Jiang, Ziyan; Zou, Yanfen; Yin, Yin; Zuo, Qing; Sun, Lizhou

    2015-10-01

    To identify changes in interleukin (IL)-6 levels and its pathway (Jak/stat3) in the human placenta during preterm and term labor, placental tissues were collected from primiparous women who underwent vaginal deliveries or cesarean sections in our hospital. The women were divided into three groups: preterm labor (n = 15), term labor (n = 15), and term not in labor (n = 15). IL-6 levels were detected by ELISA in placental supernatant, and p-STAT3 and SOCS3 protein was detected by Western blot. TUNEL was used to detect apoptosis in trophoblasts. HTR-8/SVneo cells were cultured after stimulation with IL-6, and we measured p-STAT3, SOCS3, and the rate of apoptosis. Expression of p-STAT3 and SOCS3 in the placenta and trophoblast cells showed that IL-6 levels were highest in the preterm labor group and lowest in the term not in labor group. The highest expression of placental SOCS3 protein was observed in the preterm labor group. More apoptotic cells were found in the preterm labor group than in the other two groups by TUNEL. SOCS3 and p-STAT3 expression was significantly upregulated after stimulation by IL-6 in trophoblast cells in a dose-dependent manner. However, p-STAT3 was significantly decreased after 50 ng/mL and 100 ng/mL IL-6 for 72 h. A significant increase of apoptosis was observed with treatment of 50 ng/mL IL-6 in HTR-8/SVneo cells. The role of the SOCS3 protein in the Jak/stat3 pathway is to mediate different mechanisms for preterm and term labor processes in the placenta. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. Comparing the Impact of Topical Application of Human Milk and Chlorhexidine on Cord Separation Time in Newborns

    OpenAIRE

    Abbaszadeh, Fatemeh; Hajizadeh, Zanab; Mohammad JAHANGIRI

    2016-01-01

    Objectives: The best umbilical cord care after birth is a controversial issue. Aim of this research was to compare the effect of topical application of human milk and chlorhexidin on cord separation time in newborns. Methods: One hundred seventy four neonates attending from hospitals affiliated to Kashan University of Medical Sciences were included. Newborns from birth were randomized to two groups. In group mother’s milk, mother will rub her own milk to cord stump two times a day. chlorhexid...

  9. Spinal Cord Contusion

    Institute of Scientific and Technical Information of China (English)

    Gong Ju; Jian Wang; Yazhou Wang; Xianghui Zhao

    2014-01-01

    Spinal cord injury is a major cause of disability with devastating neurological outcomes and lim-ited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.

  10. Lactation-Related MicroRNA Expression in Microvesicles of Human Umbilical Cord Blood.

    Science.gov (United States)

    Wang, De-Jing; Wang, Chen-Meiyi; Wang, Yi-Ting; Qiao, Hai; Fang, Liao-Qiong; Wang, Zhi-Biao

    2016-11-24

    BACKGROUND The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. MATERIAL AND METHODS Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and b-casein secretion was detected by ELISA. RESULTS Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of β-casein was observed after 96 h from cells exposed to MVs (PUmbilical cord blood MVs contain many lactation-related miRNAs and can induce β-casein production by HBL-100 cells in vitro. Thus, umbilical cord blood MVs may mediate secretion of β-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.

  11. Migration capacity of human umbilical cord mesenchymal stem cells towards glioma in vivo*

    Institute of Scientific and Technical Information of China (English)

    Cungang Fan; Dongliang Wang; Qingjun Zhang; Jingru Zhou

    2013-01-01

    High-grade glioma is the most common malignant primary brain tumor in adults. The poor prognosis of glioma, combined with a resistance to currently available treatments, necessitates the ment of more effective tumor-selective therapies. Stem cel-based therapies are emerging as novel cel-based delivery vehicle for therapeutic agents. In the present study, we successful y isolated human umbilical cord mesenchymal stem cel s by explant culture. The human umbilical cord senchymal stem cel s were adherent to plastic surfaces, expressed specific surface phenotypes of mesenchymal stem cel s as demonstrated by flow cytometry, and possessed multi-differentiation potentials in permissive induction media in vitro. Furthermore, human umbilical cord mesenchymal stem cel s demonstrated excel ent glioma-specific targeting capacity in established rat glioma models after intratumoral injection or contralateral ventricular administration in vivo. The excellent glioma-specific targeting ability and extensive intratumoral distribution of human umbilical cord mesenchymal stem cel s indicate that they may serve as a novel cel ular vehicle for delivering the-rapeutic molecules in glioma therapy.

  12. 水通道蛋白8在人胎盘胎膜中的表达%Aquaporin 8 expression in human placenta and fetal membrane

    Institute of Scientific and Technical Information of China (English)

    刘慧妹; 郝荣增; 宋小飞; 熊正方

    2009-01-01

    BACKGROUND: Placenta and fetal membrane play an important role In maternal-fetal homeostasis. However, the molecular and cellular mechanisms underlying water transfer across placenta and amniotic membrane remain unknown. It is hypothesized that maternal-fetal fluid exchanges via aquaporin (AQP) water channels in the placenta and fetal membrane.OBJECTIVE: To investigate AQP8 protein expression in normal human placenta and fetal membrane.DESIGN, TIME AND SETTING: A control observation was performed at the Central Laboratory of Guangzhou Medical College from July to December 2005.MATERIALS: Human placenta and fetal membrane tissues from 5 elective cesarean section deliveries of normal term pregnancies (range 37-42 weeks) were studied. Maternal age averaged (27?) years old. Experimental protocol was approved by the Hospital's Ethics Committee.METHODS: Thirty minutes after delivery, fetal membrane and placenta were dissected and washed with sterile physiological saline. Some were frozen at -80?, and the remaining tissues were fixed for 24-48 hours with 10% neutral formalin and paraffin embedded for immunohistochemical staining.MAIN OUTCOME MEASURES: AQP8 expression and distribution in human placenta and fetal membrane were detected by the reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blotting analysis.RESULTS: RT-PCR results showed that AQP8 mRNA was expressed in both placenta and fetal membrane tissues. Western blotting analysis also yielded positive results in placenta and fetal membrane with a specific band site at approximately 45 000.Immunohistochemistry results revealed that AQP8 protein was expressed in placental syncytiotrophoblasts, amniotic epithelial cells, and chorion cytotrophoblasts.CONCLUSION: At protein level, AQP8 is expressed in placental syncytiotrophoblasts, amniotic epithelial cells, and chorion cytotrophoblasts.%背景:胎盘和胎膜在母胎液体平衡过程中起着重要作用,而水穿过胎盘

  13. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Jun Yan

    2007-02-01

    Full Text Available BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major

  14. Sustained co-cultivation with human placenta-derived MSCs enhances ALK5/Smad3 signaling in human breast epithelial cells, leading to EMT and differentiation.

    Science.gov (United States)

    Yoo, Young A; Kang, Myoung Hee; Kim, Byung Soo; Kim, Jun Suk; Seo, Jae Hong

    2009-06-01

    The interaction between mammary epithelial cells and their surrounding microenvironment are important in the development of the mammary gland. Thus, mesenchymal stem cells (MSCs), which retain pluripotency for various mesenchymal lineages, may provide a permissive environment for the morphologic alteration and differentiation of mammary epithelial cells. To this end, we investigated whether the interactions between mammary epithelial cells and human placenta-derived MSCs (hPMSC) affect the morphology, proliferation, and differentiation of epithelial cells in a co-culture system. We show that after co-culture with hPMSCs, human mammary epithelial cell lines (MCF-10F and HEMC) underwent significant morphologic alterations and a dramatic increase in ductal-alveolar branching, which was accompanied by a decrease or loss of the epithelial marker E-cadherin and a gain of the mesenchymal markers, alpha-SMA and vimentin. MCF-10F and HEMC proliferation was also inhibited in the presence of hPMSCs, and this retardation in growth was due to cell cycle arrest. Furthermore, in MCF-10F and HMEC cells, hPMSCs induced the production of lipid droplets, milk fat globule protein, and milk protein lactoferrin, which are markers of functional mammary differentiation. We also noticed an elevation in ALK5 and phosphorylated Smad3 protein levels upon hPMSC co-culture. Strikingly, the changes in morphology, proliferation, and differentiation were reversed by treatment with ALK5 or Smad3 knockdown in MCF-10F/hPMSC co-cultures. Collectively, our findings suggest that co-cultivation with hPMSCs leads to epithelial to mesenchymal transition (EMT) and differentiation of human breast epithelial cells through the ALK5/Smad3 signaling pathway.

  15. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy.

    Science.gov (United States)

    Ding, Dah-Ching; Chang, Yu-Hsun; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2015-01-01

    The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton's jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications.

  16. Cobalamin analogues in humans: a study on maternal and cord blood.

    Directory of Open Access Journals (Sweden)

    Tore Forsingdal Hardlei

    Full Text Available BACKGROUND: Haptocorrin (HC carries cobalamin analogues (CorA, but whether CorA are produced in the body is unknown. All cobalamins (Cbl to the foetus are delivered by the Cbl-specific protein transcobalamin (TC, and therefore analysis of cord serum for CorA may help to clarify the origin of CorA. METHODS: HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69. RESULTS: The CorA-concentration was higher in cord serum (median = 380, range: 41-780 pmol/L than in serum from the mothers (median = 160, range: 64-330 pmol/L, (p<0.0001. HPLC-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother and 45% (cord serum of the total amount CorA, and eluted as does dicyanocobinamide. CONCLUSION: Our results support that CorA in the human body are derived from Cbl.

  17. Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Lau, Andy T.Y. [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China)

    2016-04-15

    ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

  18. Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Seyed Ruhollah Hosseini

    2016-10-01

    Full Text Available Introduction The pathophysiology of spinal cord injury (SCI has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs and Melissa officinalis (MO are useful for the prevention of neurological disease. Methods Thirty-six adult male rats were randomly divided into intact, sham, control (SCI, MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. Results The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001, sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001, and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001 were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001 was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001 and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001 in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. Conclusion The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI.

  19. Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury.

    Science.gov (United States)

    Hosseini, Seyed Ruhollah; Kaka, Gholamreza; Joghataei, Mohammad Taghi; Hooshmandi, Mehdi; Sadraie, Seyed Homayoon; Yaghoobi, Kayvan; Mohammadi, Alireza

    2016-10-01

    The pathophysiology of spinal cord injury (SCI) has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs) and Melissa officinalis (MO) are useful for the prevention of neurological disease. Thirty-six adult male rats were randomly divided into intact, sham, control (SCI), MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg) was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG) was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001), sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001), and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001) were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001) was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001) and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001) in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI. © The Author(s) 2016.

  20. 脐血、胎发、胎盘、母发303例汞含量配对测定与分析%Paired determination and analysis of 303 mercury samples of cord blood, fetal hair, placenta and maternal scalp hair

    Institute of Scientific and Technical Information of China (English)

    吕弘道; 郭俊良; 陈梅竹; 苏海兰

    2013-01-01

    目的 配对测定脐血、胎发、胎盘、母发汞含量,分析其相关性以及各种汞暴露高危因素对样本汞含量的影响.方法 对整个孕期生活在本地、无重大疾病史的入院孕妇进行健康影响因素问卷调查,所分娩新生儿(除多胎、出生缺陷外)娩出时收集脐血、胎发,同时采集胎盘组织及产妇头发行汞含量测定.结果 303例脐血、胎发、胎盘、母发汞含量均值分别为1.65 μg/kg、234.58 μg/kg、3.85 μg/kg、497.62 μg/kg,50百分位数分别为1.72 μg/kg、252.24 μg/kg、3.98 μg/kg、508.88 μg/kg.脐血汞和胎发汞、脐血汞和胎盘汞、脐血汞和母发汞、胎发汞和胎盘汞、胎发汞和母发汞、母发汞和胎盘汞均呈正相关(P均<0.05).生活在涉汞工厂附近、较多食用淡水鱼或海鱼、孕期使用增白类化妆品、接触生活燃煤和香烟等高危因素者脐血汞、胎发汞、母发汞分别为(2.24 ±0.20) μg/kg、(315.65 ±35.31) μg/kg、(663.53 ±71.83) μg/kg,未接触者分别为(1.62±0.16) μg/kg、(245.79±28.21) μg/kg、(499.39±47.72)μg/kg,2组间差异均有统计学意义(P均<0.01).结论 除地区性加强工业污染监控和治理外,孕期应增强保健意识,生活中避免接触汞暴露高危因素.脐血汞和胎发汞不仅高度相关,且均与产妇胎盘汞、母发汞显著相关.2种检测均能达到监测宫内汞暴露状况的目的.%Objective To determine mercury contents in pair in cord blood,fetal hair,placenta and maternal scalp hair,and to analyze the correlation among them and the effect of mercury exposure risk factors in the mercury contents of samples.Methods Puerperants in the hospital,who lived in the local area without history of major diseases during the whole pregnancy,were investigated by questionnaire composed to several health factors.Cord blood,fetal hair,placenta and maternal scalp hair of these puerperal and their neonates (polyembryony and birth defects excluded

  1. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    Science.gov (United States)

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

    2014-01-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  2. Localisation of glycine receptors in the human forebrain, brainstem, and cervical spinal cord: an immunohistochemical review

    Directory of Open Access Journals (Sweden)

    Kristin Baer

    2009-11-01

    Full Text Available Inhibitory neurotransmitter receptors for glycine (GlyR are heteropentameric chloride ion channels that are comprised of four functional subunits, alpha1-3 and beta and that facilitate fast-response, inhibitory neurotransmission in the mammalian brain and spinal cord. We have investigated the distribution of GlyRs in the human forebrain, brainstem, and cervical spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. This review will summarize the present knowledge on the GlyR distribution in the human brain using our established immunohistochemical techniques. The results of our immunohistochemical labeling studies demonstrated GlyR immunoreactivity (IR throughout the human basal ganglia, substantia nigra, various pontine regions, rostral medulla oblongata and the cervical spinal cord present as intense and abundant punctate IR along the membranes of the neuronal soma and dendrites. This work is part of a systematic study of inhibitory neurotransmitter receptor distribution in the human CNS, and provides a basis for additional detailed physiological and pharmacological studies on the inter-relationship of GlyR, GABAAR and gephyrin in the human brain. This basic mapping exercise, we believe, will provide important baselines for the testing of future pharmacotherapies and drug regimes that modulate neuroinhibitory systems. These findings provide new information for understanding the complexity of glycinergic functions in the human brain, which will translate into the contribution of inhibitory mechanisms in paroxysmal disorders and neurodegenerative diseases such as Epilepsy, Huntington's and Parkinson’s Disease and Motor Neuron Disease.

  3. Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus

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    Francisco Visiedo

    2017-01-01

    Full Text Available Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM. The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO. Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n=8 and GDM (n=8 pregnancies. S-Nitrosylation was measured using the biotin-switch assay, while the expression and protein activity were assessed by immunoblotting and colorimetric methods, respectively. Results indicated that catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas, and that was accompanied by reduced catalase activity. S-Nitrosylation of ERK1/2 and AKT was increased in GDM placentas, and their activities were inhibited. Activities of caspase-3 and caspase-9 were increased, with the latter also showing diminished nitrosylation levels. These findings suggest that S-nitrosylation is a little-known, but critical, mechanism by which NO directly modulates key placental proteins in women with GDM and, as a consequence, maternal and fetal anomalies during pregnancy can occur.

  4. Three-dimensional reconstruction of human spinal cord based on histological serial sections

    Institute of Scientific and Technical Information of China (English)

    Guangming Lü; Huiqun Wu; Lemin Tang; Xiao Han; Dafeng Ji; Xiaosong Gu

    2008-01-01

    BACKGROUND:It is not possible to reconstruct the inner structure of the spinal cord.such as gray matter and spinal tracts,from the Visual Human Project database or CT and MRI databases,due to low image resolution and contrast in macrosection images.OBJECTIVE:To explore a semi-automatic computerized three-dimensional(3D)reconstruction of human spinal cord based on histological serial sections,in order to solve issues such as low contrast.DESIGN,TIME AND SETTING:An experimental study combining serial section techniques and 3D reconstruction,performed in the laboratory of Hunlan Anatomy and Histoembryology at the Medical School of Nantong University during January to April 2008.SETTING:Department of Anatomy,Institute of Neurobiology,Jiangsu Province Key Laboratory of Neural Regeneration,Laboratory of Image Engineering.MATERIALS:A human lumbar spinal cord segment from fresh autopsy material of an adult male.M[ETHODS:After 4% paraformaldehyde fixation for three days,serial sections of the lumbar spinal cord were cut on a Leica cryostat and mounted on slides in sequence,with eight sections aligned separately on each slide.All sections were stained with Luxol Fast Blue to reveal myelin sheaths.After gradient dehydration and clearing,the stained slides were coverslipped.Sections were observed and images recorded under a light microscope using a digital camera.Six images were acquired at ×25 magnification and automatically stitched into a complete section image.Aftel-all serial images were obtained,96 complete serial images of the human lumbar cord segment were automatically processed with "Curves","Autocontrast","Gray scale 8 bit","Invert","Image resize to 50%"steps using Photoshop 7.0 software.All images were added in order into 3D-DOCTOR 4.0 software as a stack where serial images were automatically realigned with neighbonng images and semi-automatically segmented for white matter and gray matter.Finally,simple surface and volume reconstruction were completed on a

  5. Human cervical spinal cord funiculi: investigation with magnetic resonance diffusion tensor imaging.

    Science.gov (United States)

    Onu, Mihaela; Gervai, Patricia; Cohen-Adad, Julien; Lawrence, Jane; Kornelsen, Jennifer; Tomanek, Boguslaw; Sboto-Frankenstein, Uta Nicola

    2010-04-01

    To use spinal cord diffusion tensor imaging (DTI) for investigating human cervical funiculi, acquire axial diffusion magnetic resonance imaging (MRI) data with an in-plane resolution sufficient to delineate subquadrants within the spinal cord, obtain corresponding DTI metrics, and assess potential regional differences. Healthy volunteers were studied with a 3 T Siemens Trio MRI scanner. DTI data were acquired using a single-shot spin echo EPI sequence. The spatial resolution allowed for the delineation of regions of interest (ROIs) in the ventral, dorsal, and lateral spinal cord funiculi. ROI-based and tractography-based analyses were performed. Significant fractional anisotropy (FA) differences were found between ROIs in the dorsal and ventral funiculi (P = 0.0001), dorsal and lateral funiculi (P = 0.015), and lateral and ventral funiculi (P = 0.0002). Transverse diffusivity was significantly different between ROIs in the ventral and dorsal funiculi (P = 0.003) and the ventral and lateral funiculi (P = 0.004). Tractography-based quantifications revealed DTI parameter regional differences that were generally consistent with the ROI-based analysis. Original contributions are: 1) the use of a tractography-based method to quantify DTI metrics in the human cervical spinal cord, and 2) reported DTI values in various funiculi at 3 T. (c) 2010 Wiley-Liss, Inc.

  6. Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes

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    Laurent Roybon

    2013-09-01

    Full Text Available Differentiation of astrocytes from human stem cells has significant potential for analysis of their role in normal brain function and disease, but existing protocols generate only immature astrocytes. Using early neuralization, we generated spinal cord astrocytes from mouse or human embryonic or induced pluripotent stem cells with high efficiency. Remarkably, short exposure to fibroblast growth factor 1 (FGF1 or FGF2 was sufficient to direct these astrocytes selectively toward a mature quiescent phenotype, as judged by both marker expression and functional analysis. In contrast, tumor necrosis factor alpha and interleukin-1β, but not FGFs, induced multiple elements of a reactive inflammatory phenotype but did not affect maturation. These phenotypically defined, scalable populations of spinal cord astrocytes will be important both for studying normal astrocyte function and for modeling human pathological processes in vitro.

  7. Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Vorkamp, Katrin; Mathiesen, Line

    2010-01-01

    BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very...... high concern due to critical windows in fetal development. METHODS: A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored....... CONCLUSION: The transport of BDE-47 and BDE-99 indicates in utero exposure to these congeners. Although the transport of BDE-209 was limited, however, possible metabolic debromination may lead to products which are both more toxic and transportable. Our study demonstrates fetal exposure to PBDEs, which...

  8. NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury

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    Schoenen Jean

    2009-07-01

    Full Text Available Abstract Background A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs. Experimental spinal cord injury (SCI has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord. Methods An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. Results In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan. Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres

  9. Prostasin and its regulatory proteins in human placentas from pregnant women with preeclampsia and healthy pregnant controls

    DEFF Research Database (Denmark)

    Frederiksen-Møller, Britta; Jørgensen, Jan Stener; Vogel, Lotte Katrine;

    2015-01-01

    for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized...... that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. METHODS: This hypothesis was addressed in a cross-sectional design with 20 healthy pregnant women and 20 women with new onset of preeclampsia (hypertension and 1......+ for protein on urine dipstick). Blood and urine samples were obtained in relation to delivery and placental biopsies were taken immediately after delivery (control = 39 and preeclampsia 40 weeks). RESULTS: Women with preeclampsia displayed lower levels of aldosterone in plasma (p=0.0475) and in spot urine...

  10. Expression of metalloproteinases 1, 2, 7, 9, and 12 in human cytotrophoblastic cells from normal and preeclamptic placentas.

    Science.gov (United States)

    Cohen, Marie; Ribaux, Pascale; Epiney, Manuella; Irion, Olivier

    2012-01-01

    Preeclampsia is a specific pregnancy disorder which could be due, at least in part, to impaired invasion of trophoblastic cells. Since matrix metalloproteinases (MMPs) are the predominant proteases involved in trophoblastic invasion, we investigated and compared expression of MMP-1, 2, 7, 9 and 12 of cytotrophoblastic cells (CTB) purified from preeclamptic (PE) placentas to control CTB. In order to evaluate invasive properties of cells, purified CTB were seeded on collagen-coated insert following boyden chamber principle and matrix metalloproteinases (MMPs) expression was evaluated by qPCR. Our results showed that PE CTB are less invasive than control CTB in vitro. In parallel, expression of MMPs, except for MMP-2, tends to be decreased in PE CTB compared to control CTB. At the exception of MMP-2, this study confirms the importance of MMPs in development of PE.

  11. Autophagy and Human Parturition: Evaluation of LC3 Expression in Placenta from Spontaneous or Medically Induced Onset of Labor

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    Laura Avagliano

    2013-01-01

    Full Text Available Induction of labor is one of the most used procedures in obstetrics, performed to achieve vaginal delivery through cervical ripening and stimulation of uterine contractions. We investigated the impact of induction of labor upon placental autophagy, a catabolic pathway activated in response to alteration of the physiological intracellular conditions. We collected 28 singleton placentas at the time of uncomplicated term vaginal delivery (7 spontaneous onset of labor, 21 induced labor. Autophagy was evaluated by immunohistochemistry, immunofluorescence, and immunoblotting. No significant difference in the autophagy expression was found between spontaneous or induced onset of labor. We found an inverse relationship between autophagy expression and the maternal prepregnancy body mass index, irrespective of the mode of labor onset. This result could be related to the nutritional maternal habits before and throughout pregnancy rather than rapid metabolic changes during labor.

  12. Caracterización del canal epitelial de sodio en sinciciotrofoblasto de placenta humana preeclamptica Characterization of the epithelial sodium channel in human pre-eclampsia syncytiotrophoblast

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    Silvana del Mónaco

    2006-02-01

    Full Text Available El sinciciotrofoblasto (SCT de placenta humana regula la transferencia de solutos y agua entre la sangre fetal y materna. En el presente trabajo observamos que el canal de sodio ENaC (asociado a cuadros como el síndrome de Liddle y pseudohipoaldosteronismo está presente en la membrana apical del SCT y que la subunidad a del canal tiene una expresión reducida en placentas con hipertensión gestacional (preeclampsia. Realizamos estudios a nivel de expresión de ARN (RT-PCR y a nivel proteico (western blot e inmunohistoquímica. En la línea celular BeWo (modelo de SCT humano el canal se encuentra presente y la expresión del mismo es regulada por las hormonas aldosterona, vasopresina, estradiol y progesterona. Analizamos la actividad del ENaC por electrofisiología y observamos corrientes sensibles a amiloride (10 µM cuando las células BeWo se cultivaron 12 horas con aldosterona (100 nM. Esta corriente presentó una magnitud 20 veces mayor que las corrientes basales, un potencial de reversión cercano a 3 mV y una conductancia de 127 ± 26 pS/pF entre los pulsos de -60 y -140 mV aplicados. Las características de esta corriente son similares a las producidas por ENaC en otros tejidos y evidencian la presencia de un canal funcional. El papel del ENaC en el SCT es poco comprendido, aunque la diferencia de expresión en la preeclampsia podría tener consecuencias para el transporte placentario de agua y iones. Nuestros datos son un aporte para futuros estudios de los mecanismos involucrados en la patofisiología de la preeclampsia.The syncytiotrophoblast (SCT, a multinucleated epithelium forming the outer layer of chorionic villi, acts in human placenta as a transporting barrier regulating the transference of nutrients, solutes and water between maternal and fetal blood. Electrolyte homeostasis and extracellular fluid volume are maintained primarily by regulated Na+ transport. The present study was conducted to analyze the presence of the

  13. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    Science.gov (United States)

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  14. Myometrial contractility influences oxytocin receptor (OXTR) expression in term trophoblast cells obtained from the maternal surface of the human placenta.

    Science.gov (United States)

    Szukiewicz, Dariusz; Bilska, Anna; Mittal, Tarun Kumar; Stangret, Aleksandra; Wejman, Jaroslaw; Szewczyk, Grzegorz; Pyzlak, Michal; Zamlynski, Jacek

    2015-09-16

    Oxytocin (OXT) acts through its specific receptor (OXTR) and increased density of OXTR and/or augmented sensitivity to OXT were postulated as prerequisites of normal onset of labor. Expression of OXTR in the placental term trophoblast cells has not yet been analyzed in the context of contractile activity of the uterus. Here we examine comparatively OXT contents in the placental tissue adjacent to the uterine wall and expressions of OXTR in this tissue and corresponding isolated placental trophoblast cells. Twenty eight placentae after normal labors at term (group I, N = 14) and after cesarean sections performed without uterine contractile activity (group II, N = 14) have been collected. Tissue excised from the maternal surface of examined placenta was used for OXT concentration measurement, cytotrophoblast cell cultures preparation and immunohistochemistry of OXTR. Concentration of OXT was estimated in the tissue homogenates by an enzyme immunoassay with colorimetric detection. Cytotrophoblast cells were isolated using Kliman's method based on trypsin, DNase, and a 5-70% Percoll gradient centrifugation. The cultures were incubated for 5 days in normoxia. Both placental specimens and terminated cytotrophoblast cultures were fixed and embedded in paraffin before being immunostained for OXTR. Using light microscopy with computed morphometry for quantitative analysis, OXTR expressions were estimated in calibrated areas of the paraffin sections. There were not significant differences between the groups in respect to the mean OXT concentration. However, in both groups the median value of OXT concentration was significantly (p labor with efficient contractile activity (vaginal delivery). Further studies may disclose if this local OXT/OXTR signaling is utilized in the third stage of labor to elicit placental detachment or contribute in a more versatile way throughout the labor period.

  15. Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta.

    Science.gov (United States)

    Mareschi, Katia; Castiglia, Sara; Sanavio, Fiorella; Rustichelli, Deborah; Muraro, Michela; Defedele, Davide; Bergallo, Massimiliano; Fagioli, Franca

    2016-02-01

    Mesenchymal stromal cells (MSCs) are a promising tool in cell therapies because of their multipotent, bystander, and immunomodulatory properties. Although bone marrow represents the main source of MSCs, there remains a need to identify a stem cell source that is safe and easily accessible and yields large numbers of cells without provoking debates over ethics. In this study, MSCs isolated from amniotic fluid and placenta were compared with bone marrow MSCs. Their immunomodulatory properties were studied in total activated T cells (peripheral blood mononuclear cells) stimulated with phytohemagglutinin (PHA-PBMCs). In particular, an in vitro co-culture system was established to study: (i) the effect on T-lymphocyte proliferation; (ii) the presence of T regulatory lymphocytes (Treg); (iii) the immunophenotype of various T subsets (Th1 and Th2 naïve, memory, effector lymphocytes); (iv) cytokine release and master gene expression to verify Th1, Th2, and Th17 polarization; and (v) IDO production. Under all co-culture conditions with PHA-PBMCs and MSCs (independently of tissue origin), data revealed: (i) T proliferation inhibition; (ii) increase in naïve T and decrease in memory T cells; (iii) increase in T regulatory lymphocytes; (iv) strong Th2 polarization associated with increased interleukin-10 and interleukin-4 levels, Th1 inhibition (significant decreases in interleukin-2, tumor necrosis factor-α, interferon-γ, and interleukin-12) and Th17 induction (production of high concentrations of interleukins-6 and -17); (v) indoleamine-2,3-dioxygenase mRNA induction in MSCs co-cultured with PHA-PBMCs. AF-MSCs had a more potent immunomodulatory effect on T cells than BM-MSCs, only slightly higher than that of placenta MSCs. This study indicates that MSCs isolated from fetal tissues may be considered a good alternative to BM-MSCs for clinical applications.

  16. A Simple Method to Isolate and Expand Human Umbilical Cord Derived Mesenchymal Stem Cells: Using Explant Method and Umbilical Cord Blood Serum.

    Science.gov (United States)

    Hassan, Ghmkin; Kasem, Issam; Soukkarieh, Chadi; Aljamali, Majd

    2017-08-31

    Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from umbilical cords and are therapeutically used because of their ability to differentiate into various types of cells, in addition to their immunosuppressive and anti-inflammatory properties. Fetal bovine serum (FBS), considered as the standard additive when isolating and culturing MSCs, has a major limitation related to its animal origin. Here, we employed a simple and economically efficient protocol to isolate MSCs from human umbilical cord tissues without using digestive enzymes and replacing FBS with umbilical cord blood serum (CBS). MSCs were isolated by culturing umbilical cord pieces in CBS or FBS supplemented media. Expansion and proliferation kinetics of cells isolated by explant method in the presence of either FBS or CBS were measured, with morphology and multi-differentiation potential of expanded cells characterized by flow cytometry, RT-PCR, and immunofluorescence. MSCs maintained morphology, immunophenotyping, multi-differentiation potential, and self-renewal ability, with better proliferation rates for cells cultured in CBS compared to FBS supplement media. We here present a simple, reliable and efficient method to isolate MSCs from umbilical cord tissues, where cells maintained proliferation, differentiation potential and immunophenotyping properties and could be efficiently expanded for clinical applications.

  17. A novel cortical target to enhance hand motor output in humans with spinal cord injury.

    Science.gov (United States)

    Long, Jinyi; Federico, Paolo; Perez, Monica A

    2017-06-01

    A main goal of rehabilitation strategies in humans with spinal cord injury is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following spinal cord injury, the role of cortical targets remain poorly understood. Here, we use 180 pairs of transcranial magnetic stimulation for ∼30 min over the hand representation of the motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order. Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following spinal cord injury. Motor evoked potentials elicited by transcranial magnetic stimulation, paired-pulse intracortical inhibition, spinal motor neuron excitability (F-waves), index finger abduction force and electromyographic activity as well as a hand dexterity task were measured before and after both protocols in 15 individuals with chronic incomplete cervical spinal cord injury and 17 uninjured participants. We found that motor evoked potentials size increased in spinal cord injury and uninjured participants after the I-wave but not the control protocol for ∼30 to 60 min after the stimulation. Intracortical inhibition decreased and F-wave amplitude and persistence increased after the I-wave but not the control protocol, suggesting that cortical and subcortical networks contributed to changes in corticospinal excitability. Importantly, hand motor output and hand dexterity increased in individuals with spinal cord injury after the I-wave protocol. These results provide the first evidence that late synaptic input to corticospinal neurons may represent a novel therapeutic target for improving motor function

  18. Differentiation and tumorigenicity of neural stem cells from human cord blood mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Jing Xiang; Changming Wang; Jingzhou Wang

    2009-01-01

    BACKGROUND:Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissues and exhibit low immunogenicity.OBJECTIVE:To investigate isolation and in vitro cultivation methods of human cord blood MSCs,to observe expression of neural stem cell (NSC) marker mRNA under induction,and to detect tumorigenicity in animals.DESIGN,TIME AND SETTING:A cell biological,in vitro trial and a randomized,controlled,in vivo experiment were performed at the Department of Neurology,Daping Hospital at the Third Military Medical University of Chinese PLA from August 2006 to May 2008.MATERIALS:Umbilical cord blood was collected from full-term-delivery fetus at the Department of Gynecology and Obstetrics of DapJng Hospital,China.Eighteen BALB/C nu/nu nude mice were randomly assigned to three groups:back subcutaneous,cervical subcutaneous,and control,with 6 mice in each group.METHODS:Monocytes were isolated from heparinized human cord blood samples by density gradient centrifugation and then adherent cultivated in vitro to obtain MSC clones.After the cord blood MSCs were cultured for 7 days with nerve growth factor and retinoic acid to induce differentiation into NSCs,the cells (adjusted density of 1×10~7/mL) were prepared into cell suspension.In the back subcutaneous and cervical subcutaneous groups,nude mice were hypodermically injected with a 0.5-mL cell suspension into the back and cervical regions,respectively.In the control group,nude mice received a subcutaneous injection of 0.5 mL physiological saline into the back or cervical regions,respectively.MAIN OUTCOME MEASURES:Cellular morphology was observed by inverted microscopy,cultured cord blood MSCs were examined by flow cytometry,expression of nestin and musashi-1 mRNA was detected by reverse-transcriptase polymerase chain reaction prior to and after induction,and tumorigenicity following cord blood MSC transplantation was assayed by hematoxylin-eosin staining.RESULTS:Following adherent cultivation

  19. Differentiation of Human Cord Blood and Stromal Derived Stem Cells into Neuron Cells

    Directory of Open Access Journals (Sweden)

    Özlem Pamukçu Baran

    2007-01-01

    Full Text Available The most basic properties of stem cells are the capacities to self-renew indefinitely and to differentiate into multiple cell or tissue types. Umbilical cord blood has been utilized for human hematopoietic stem cell transplantation as an alternative source to bone marrow.The experiments show that Wharton’s jelly cells are easily attainable and can be expanded in vitro, maintained in culture, and induced to differentiate into neural cells. Almost recent studies it has been discovered that the cord blood-derived cells can differantiate not only to blood cells but also to various somatic cells like neuron or muscle cell with the signals taken from the envoirenment.Interestingly, neural cells obtained from umbilical cord blood show a relatively high spontaneous differentiation into oligodendrocytes, Embryonic stem cells proliferate indefinitely and can differentiate spontaneously into all tissue types.It has been shown that embryonic stem cells can be induced to differentiate into neurons and glia by treatment with retinoic acid or basic fibroblast growth factor. It has been studied that the diseases as Motor Neuron Disease, Parkinson, Alzheimer and degeneration of medulla spinalis and also paralysises could be treated with transplantation of cord blood-dericed stem cells.

  20. Generation, Expansion, and Differentiation of Human Induced Pluripotent Stem Cells (hiPSCs) Derived From the Umbilical Cords of Newborns.

    Science.gov (United States)

    Song, Richard S; Carroll, Jeanne M; Acevedo, Lisette; Wu, Dongmei; Liu, Yang; Snyder, Evan Y

    2014-05-16

    The umbilical cord is tissue that is normally discarded after the delivery of the infant, but it has been shown to be a rich source of stem cells from the cord blood, Wharton's jelly, and umbilical endothelial cells. Patient-specific human induced pluripotent stem cells (hiPSCs) reprogrammed from patient specific human umbilical vein endothelial cells in the neonatal intensive care unit (NICU) population (specifically, premature neonates) have not been shown in the literature. This unit describes a protocol for the generation and expansion of hiPSCs originating from umbilical cords collected from patients in the NICU.

  1. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    OpenAIRE

    Beatriz Paniagua-Torija; Angel Arevalo-Martin; Isidro Ferrer; Eduardo Molina-Holgado; Daniel Garcia-Ovejero

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqma...

  2. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Stephen J A Davies

    Full Text Available Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human

  3. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

    Science.gov (United States)

    Davies, Stephen J A; Shih, Chung-Hsuan; Noble, Mark; Mayer-Proschel, Margot; Davies, Jeannette E; Proschel, Christoph

    2011-03-02

    Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human astrocytes that

  4. Functional exploration of the human spinal cord during voluntary movement and somatosensory stimulation.

    Science.gov (United States)

    Summers, Paul E; Iannetti, Gian Domenico; Porro, Carlo A

    2010-10-01

    Demonstrations of the possibility of obtaining functional information from the spinal cord in humans using functional magnetic resonance imaging (fMRI) have been growing in number and sophistication, but the technique and the results that it provides are still perceived by the scientific community with a greater degree of scepticism than fMRI investigations of brain function. Here we review the literature on spinal fMRI in humans during voluntary movements and somatosensory stimulation. Particular attention is given to study design, acquisition and statistical analysis of the images, and to the agreement between the obtained results and existing knowledge regarding spinal cord anatomy and physiology. A striking weakness of many spinal fMRI studies is the use of small numbers of subjects and of time-points in the acquired functional image series. In addition, spinal fMRI is characterised by large physiological noise, while the recorded functional responses are poorly characterised. For all these reasons, spinal fMRI experiments risk having low statistical power, and few spinal fMRI studies have yielded physiologically relevant information. Thus, while available evidence indicates that spinal fMRI is feasible, we are only approaching the stage at which the technique can be considered to have been rigorously established as a viable means of noninvasively investigating spinal cord functioning in humans.

  5. Mesenchymal stem cells from human umbilical cord ameliorate testicular dysfunction in a male rat hypogonadism model

    Directory of Open Access Journals (Sweden)

    Zhi-Yuan Zhang

    2017-01-01

    Full Text Available Androgen deficiency is a physical disorder that not only affects adults but can also jeopardize children′s health. Because there are many disadvantages to using traditional androgen replacement therapy, we have herein attempted to explore the use of human umbilical cord mesenchymal stem cells for the treatment of androgen deficiency. We transplanted CM-Dil-labeled human umbilical cord mesenchymal stem cells into the testes of an ethane dimethanesulfonate (EDS-induced male rat hypogonadism model. Twenty-one days after transplantation, we found that blood testosterone levels in the therapy group were higher than that of the control group (P = 0.037, and using immunohistochemistry and flow cytometry, we observed that some of the CM-Dil-labeled cells expressed Leydig cell markers for cytochrome P450, family 11, subfamily A, polypeptide 1, and 3-β-hydroxysteroid dehydrogenase. We then recovered these cells and observed that they were still able to proliferate in vitro. The present study shows that mesenchymal stem cells from human umbilical cord may constitute a promising therapeutic modality for the treatment of male hypogonadism patients.

  6. Intracellular Immunization of Human Fetal Cord Blood Stem/Progenitor Cells with a Ribozyme Against Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Yu, Mang; Leavitt, Mark C.; Maruyama, Midori; Yamada, Osamu; Young, Dennis; Ho, Anthony D.; Wong-Staal, Flossie

    1995-01-01

    Successful treatment of human immunodeficiency virus infection may ultimately require targeting of hematopoietic stem cells. Here we used retroviral vectors carrying the ribozyme gene to transduce CD34^+ cells from human fetal cord blood. Transduction and ribozyme expression had no apparent adverse effect on cell differentiation and/or proliferation. The macrophage-like cells, differentiated from the stem/progenitor cells in vitro, expressed the ribozyme gene and resisted infection by a macrophage tropic human immunodeficiency virus type 1. These results suggest the feasibility of stem cell gene therapy for human immunodeficiency virus-infected patients.

  7. Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    Xiao-Peng Tang; Min Zhang; Xu Yang; Li-Min Chen; Yang Zeng

    2006-01-01

    AIM: To study the condition and potentiality of human umbilical cord blood stem cells (HUCBSC) to differentiate into hepatocytes in vivo or in vitro.METHODS: In a cell culture study of human umbilical cord blood stem cell (HUCBSC) differentiation, human umbilical cord blood mononuclear cells (HUCBMNC) were separated by density gradient centrifugation.Fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) and the supernatant of fetal liver were added in the inducing groups. Only FGF was added in the control group. The expansion and differentiation of HUCBMNC in each group were observed. Human alpha fetoprotein (AFP) and albumin (ALB) were detected by immunohistochemistry. In the animal experiments, the survival SD rats with acute hepatic injury after carbon tetrachloride (CCL4) injection 48 h were randomly divided into three groups. The rats in group A were treated with human umbilical cord blood serum. The rats in group B were treated with HUCBMNC transplantation. The rats in group C were treated with HUCBMNC transplantation followed by intraperitoneal cyclophosphamide for 7 d.The rats were killed at different time points after the treatment and the liver tissue was histopathologically studied and human AFP and ALB detected by immunohistochemistry. The human X inactive-specific transcript gene fragment in the liver tissue was amplified by PCR to find human DNA.RESULTS: The results of cell culture showed that adherent cells were stained negative for AFP or ALB in control group. However, the adherent cells in the inducing groups stained positive for AFP or ALB. The result of animal experiment showed that no human AFP or ALB positive cells present in the liver tissue of group A (control group). However, many human AFP or ALB positive cells were scattered around sinus hepaticus and the central veins of hepatic lobules and in the portal area in group B and group C after one month. The fragment of human X chromagene could be detected in the liver tissue of

  8. Transport of benzo[alpha]pyrene in the dually perfused human placenta perfusion model: effect of albumin in the perfusion medium

    DEFF Research Database (Denmark)

    Mathiesen, Line; Rytting, Erik; Mose, Tina

    2009-01-01

    P is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg...

  9. An experimental study of preventing and treating acute radioactive enteritis with human umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Rui Wang; Wei Yuan; Qiang Zhao; Peng Song; Ji Yue; Shi-De Lin; Ting-Bao Zhao

    2013-01-01

    Objective:To test the curative effect of human umbilical cord-derived mesenchymal stem cells on rat acute radioactive enteritis and thus to provide clinical therapeutic basis for radiation sickness.Methods:Human umbilical cord-derived mesenchymal stem cells were cultivatedin vitro and the model of acute radioactive enteritis of rats was established.Then, the umbilical cord mesenchymal stem cells were injected into the rats via tail vein.Visual and histopathological changes of the experimental rats were observed.Results:After the injection, the rats in the prevention group and treatment group had remarkably better survival status than those in the control group.The histological observations revealed that the former also had better intestinal mucosa structure, more regenerative cells and stronger proliferation activity than the latter.Conclusions:Human umbilical cord-derived mesenchymal stem cells have a definite therapeutic effect on acute radioactive enteritis in rats.

  10. Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication

    Directory of Open Access Journals (Sweden)

    Gong D

    2013-08-01

    Full Text Available Dianrong Gong,1 Haiyan Yu,1 Weihua Wang,2 Haixin Yang,1 Fabin Han1,21Department of Neurology, 2Centre for Stem Cells and Regenerative Medicine, Liaocheng People's Hospital, The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of ChinaAbstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI. The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy.Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE

  11. Enhancing endogenous stem cells in the newbornvia delayed umbilical cord clamping

    Institute of Scientific and Technical Information of China (English)

    Christopher Lawton; Sandra Acosta; Nate Watson; Chiara Gonzales-Portillo; hTeo Diamandis; Naoki Tajiri; Yuji Kaneko; Paul R. Sanberg; Cesar V. Borlongan

    2015-01-01

    There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal beneifts including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deifciency anemia in term infants. Human umbilical cord blood con-tains signiifcant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en-hances blood lfow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant’s susceptibility to both neonatal and age-related diseases.

  12. Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping

    Directory of Open Access Journals (Sweden)

    Christopher Lawton

    2015-01-01

    Full Text Available There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood contains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it enhances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant′s susceptibility to both neonatal and age-related diseases.

  13. Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping.

    Science.gov (United States)

    Lawton, Christopher; Acosta, Sandra; Watson, Nate; Gonzales-Portillo, Chiara; Diamandis, Theo; Tajiri, Naoki; Kaneko, Yuji; Sanberg, Paul R; Borlongan, Cesar V

    2015-09-01

    There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood contains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it enhances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant's susceptibility to both neonatal and age-related diseases.

  14. Human umbilical cord Wharton's Jelly-derived mesenchymal stem cells differentiation into nerve-like cells

    Institute of Scientific and Technical Information of China (English)

    MA Lian; FENG Xue-yong; CUI Bing-lin; Frieda Law; JIANG Xue-wu; YANG Li-ye; XIE Qing-dong; HUANG Tian-hua

    2005-01-01

    Background The two most basic properties of mesenchymal stem cells (MSCs) are the capacities to self-renew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton's Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton's Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton's Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and β-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate. The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy (EM), and laser scanning confocal microscopy (LSCM) .The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results MSCs in the Wharton's Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease (GVHD)-related cells. Treatment with Salvia miltiorrhiza caused Wharton's Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia miltiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulinⅢ, neurofilament (NF) and glial fibrillary acidic protein (GFAP). It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical

  15. Methods of isolation, expansion, differentiating induction and preservation of human umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LI Dong-rui; CAI Jian-hui

    2012-01-01

    Objective This literature review aims to summarize the methods of isolation,expansion,differentiation and preservation of human umbilical cord mesenchymal stem cells (hUCMSCs),for comprehensive understanding and practical use in preclinical research and clinical trials.Data sources All the literature reviewed was published over the last 10 years and is listed in PubMed and Chinese National Knowledge Infrastructure (CNKI).Studies were retrieved using the key word "human umbilical cord mesenchymal stem cells".Results Explants culture and enzymatic digestion are two methods to isolate hUCMSCs from WJ and there are modifications to improve these methods.Culture conditions may affect the expansion and differentiating orientations of hUCMSCs.In addition,hUCMSCs can maintain their multi-potential effects after being properly frozen and thawed.Conclusion Considering their multi-potential,convenient and non-invasive accessibility,low immunogenicity and the reported therapeutic effects in several different preclinical animal models,hUCMSCs have immense scope in regeneration medicine as a substitute for MSCs derived from bone marrow or umbilical cord blood.

  16. Placenta: How It Works, What's Normal

    Science.gov (United States)

    ... the most common placental problems include placental abruption, placenta previa and placenta accreta. These conditions can cause potentially ... nutrients. In some cases, early delivery is needed. Placenta previa. This condition occurs when the placenta partially or ...

  17. Differentiation of the nuclear groups in the posterior horn of the human embryonic spinal cord.

    Science.gov (United States)

    Pytel, A; Bruska, M; Woźniak, W

    2011-11-01

    The formation of nuclear groups in the posterior horns of the human embryonic spinal cord was traced in serial sections of embryos of developmental stages 13 to 23 (32 to 56 postovulatory days). The following observations, new for the human, are presented: 1. The differentiation of the neural tube into 3 zones (germinal, mantle and marginal) is detected in the middle of the 5(th) week. 2. The primordia of the posterior horns are marked at stage 14 (33 days). 3. In the middle of the 7(th) week the nucleus proprius and substantia gelatinosa are discerned. 4. Differentiation of the nuclei within the posterior horns proceeds in the ventrodorsal and rostrocaudal gradients.

  18. Sexual dimorphism in human and canine spinal cord: role of early androgen.

    Science.gov (United States)

    Forger, N G; Breedlove, S M

    1986-10-01

    Onuf's nucleus, located in the sacral spinal cord of dogs, cats, and primates, innervates perineal muscles involved in copulatory behavior. A sexual dimorphism in Onuf's nucleus was found in humans and dogs: males have significantly more motoneurons in this nucleus than do females. Prenatal androgen treatment of female dogs eliminated the dimorphism. In the homologous nucleus in rats, a similar effect of androgen has been shown to involve sparing of motoneurons from cell death. These results establish a morphological sex difference in a human central nervous system region of known function; well-studied animal models suggest explanations of the development of this dimorphism.

  19. Schwannosis: role of gliosis and proteoglycan in human spinal cord injury.

    Science.gov (United States)

    Bruce, J H; Norenberg, M D; Kraydieh, S; Puckett, W; Marcillo, A; Dietrich, D

    2000-09-01

    Schwannosis (aberrant proliferation of Schwann cells and nerve fibers) has been reported following spinal cord injury (SCI). In this study, we examined the incidence of schwannosis following human SCI, and investigated its relationship to gliosis. We found evidence of schwannosis in 32 out of 65 cases (48%) of human SCI that survived 24 h to 24 years after injury; this incidence rose to 82% in those patients who survived for more than 4 months. Schwannosis was not observed in cases that survived less than 4 months after injury. In affected cases, it was generally noted in areas that had low immunoreactivity for glial fibrillary acidic protein (GFAP), suggesting that reduced gliosis might have contributed to the aberrant proliferation of Schwann cells following SCI. Since chondroitin sulfate proteoglycan (CSPG) has been proposed to play a role in Schwann cell/glial interaction, we performed immunohistochemical staining for CSPG to investigate its potential relationship with schwannosis. CSPG in the injured cord was generally associated with the blood vessel walls, but was also sometimes noted in reactive astrocytes. In SCI with schwannosis, CSPG staining was more prominent and confined largely to the extracellular matrix and basal lamina of proliferating Schwann cells. Our study suggests that Schwann cells, which may have been displaced from spinal roots and introduced into the injured cord through a break in the pial surface, are capable of proliferating and producing CSPG, particularly in the setting of reduced gliosis. Since CSPG has been associated with inhibition of neurite outgrowth, its increased production by aberrant Schwann cells may impair spinal cord regeneration after injury.

  20. Characteristics of glucose transport across the microvillous membranes of human term placenta Características del transporte de glucosa a través de las membranas con microvellosidades de la placenta humana a término

    Directory of Open Access Journals (Sweden)

    Ravinderjit Kaur Anand

    2006-02-01

    Full Text Available Transport characteristics of D-glucose were studied in the microvillous vesicles isolated from the human term placenta. Transport occurred by selective and rapid facilitated diffusion system which was inhibitable by phloretin and HgCl2. The transport was dependent on a transmembrane. Na+-gradient indicating a "secondary active transport" system operating. The transport influx was saturable and the kinetic analysis based on Hanes-Woolf plot produced a kt and Jmax value of 1.2 mM and 34 nmoles. mgprotein-1.min-1, respectively. The efflux of D-glucose from the membrane vesicles in a pre-equilibrated assay conditions showed a distinct biphasic pattern differing significantly in the half time efflux. The t1/2 of the fast and slow components was found to be 15 sec and 660 sec, respectively. The transport showed distinct sensitivity to temperature and the Ea values both below and above the transition temperature of 37 ºC, as calculated from the Arrhenius plot were found to be 7600 and 5472 kCa1.mol-1, respectively. Inhibition studies with a number of sugars for hexose transport pathway showed that the glucose epimers, phosphorylated sugars, and even the disaccharides and the pentose sugars competed effectively with D-glucose. The influx was also inhibited by a number of steroids such as progesterone, 17α-hydroxyprogesterone, testosterone and estrogen. Insulin was found to increase glucose transport in a dose- dependent fashion at a concentration of 0.2-1 unit.ml-1. Ouabain, dinitrophenoi and nicotine strongly inhibited D-glucose uptake in the membrane vesicles.Se estudiaron las características del transporte de la D-glucosa en las vesículas con microvellosidades aisladas de la placenta humana a término. El transporte ocurría por un sistema de difusión selectiva y facilitada rápida que podía inhibirse por floretina y por HgCl2. El transporte dependía de un gradiente de Na+ transmembrana,indicativo de un sistema operativo de "transporte activo

  1. More Than Clinical Waste? Placenta Rituals Among Australian Home-Birthing Women

    OpenAIRE

    Burns, Emily

    2014-01-01

    The discursive construction of the human placenta varies greatly between hospital and home-birthing contexts. The former, driven by medicolegal discourse, defines the placenta as clinical waste. Within this framework, the placenta is as much of an afterthought as it is considered the “afterbirth.” In home-birth practices, the placenta is constructed as a “special” and meaningful element of the childbirth experience. I demonstrate this using 51 in-depth interviews with women who were pregnant ...

  2. Management of placenta percreta

    DEFF Research Database (Denmark)

    Clausen, Caroline; Lönn, Lars; Langhoff-Roos, Jens

    2014-01-01

    in the management of the conditions. A PubMed search was performed in April 2013 and the final review included 119 published placenta percreta cases. Conservative management, where the placenta is left in situ for resorption, seems to be associated with severe long-term complications of hemorrhage and infections...... cases for the local resection technique might in part explain the lower complication rates with that approach. Future prospective data collection activities should include intended as well as actual management, and long-term follow-up of all cases is of vital importance....

  3. Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Kazuya Kitamura

    Full Text Available Many therapeutic interventions for spinal cord injury (SCI using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF, which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.

  4. Human umbilical cord hyaluronate. Neutral sugar content and carbohydrate-protein linkage studies.

    Science.gov (United States)

    Varma, R; Varma, R S; Allen, W S; Wardi, A H

    1975-07-14

    Paper chromatography of neutral sugars and gas chromatography of their aldononitrile acetates indicated the presence of fucose, arabinose and a small amount of glucose in purified human umbilical cord hyaluronate. The molar ratios of serine, threonine and aspartic acid to neutral sugars were not unity, suggesting the non-involvement of the neutral sugars and the amino acids in a carbohydrate-protein linkage. The same was indicated by an increase in the percentage of the aforementioned amino acids and by the absence of sugar alditols in umbilical cord hyaluronate reduced eith NaBH4 -PdCl2, after alkali treatment. This reduction caused a decrease in the intrinsic viscosity and molecular wieght to about one-half and an appreciable decrease in the specific rota tion of hyaluronate, suggesting a separation of the two antiparallel chains o the double helical hyaluronate. The umbilical cord hyluronate containe contained bound silicon and it is possible that this bound silicon may cross-link the two chains at interspersed intervals through the uronic acid moiety and/or through neutral sugars.

  5. Plasticity of Corticospinal Neural Control after Locomotor Training in Human Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Maria Knikou

    2012-01-01

    Full Text Available Spinal lesions substantially impair ambulation, occur generally in young and otherwise healthy individuals, and result in devastating effects on quality of life. Restoration of locomotion after damage to the spinal cord is challenging because axons of the damaged neurons do not regenerate spontaneously. Body-weight-supported treadmill training (BWSTT is a therapeutic approach in which a person with a spinal cord injury (SCI steps on a motorized treadmill while some body weight is removed through an upper body harness. BWSTT improves temporal gait parameters, muscle activation patterns, and clinical outcome measures in persons with SCI. These changes are likely the result of reorganization that occurs simultaneously in supraspinal and spinal cord neural circuits. This paper will focus on the cortical control of human locomotion and motor output, spinal reflex circuits, and spinal interneuronal circuits and how corticospinal control is reorganized after locomotor training in people with SCI. Based on neurophysiological studies, it is apparent that corticospinal plasticity is involved in restoration of locomotion after training. However, the neural mechanisms underlying restoration of lost voluntary motor function are not well understood and translational neuroscience research is needed so patient-orientated rehabilitation protocols to be developed.

  6. A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta).

    Science.gov (United States)

    Salegio, Ernesto A; Bresnahan, Jacqueline C; Sparrey, Carolyn J; Camisa, William; Fischer, Jason; Leasure, Jeremi; Buckley, Jennifer; Nout-Lomas, Yvette S; Rosenzweig, Ephron S; Moseanko, Rod; Strand, Sarah; Hawbecker, Stephanie; Lemoy, Marie-Josee; Haefeli, Jenny; Ma, Xiaokui; Nielson, Jessica L; Edgerton, V R; Ferguson, Adam R; Tuszynski, Mark H; Beattie, Michael S

    2016-03-01

    The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies.

  7. De placenta bij rhesus antagonisme

    NARCIS (Netherlands)

    Wormgoor, Bernard Hendrikus

    1952-01-01

    In de inleiding worden de te behandelen problemen aan de orde gesteld. Het uitganspunt hiervan is de studie van de morphologie van de placenta. Bij het histologisch onderzoek van de placenta waren het vooral de afwijkingen in de placenta bij Erythroblastosis Foetalis (verderop aan te duiden als E.F.

  8. Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord.

    Science.gov (United States)

    Hofstoetter, Ursula S; Danner, Simon M; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-07-01

    In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22-60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5-26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits. Copyright © 2015 the American Physiological Society.

  9. Cryopreserved human umbilical cord patch for in-utero spina bifida repair.

    Science.gov (United States)

    Papanna, R; Moise, K J; Mann, L K; Fletcher, S; Schniederjan, R; Bhattacharjee, M B; Stewart, R J; Kaur, S; Prabhu, S P; Tseng, S C G

    2016-02-01

    To identify a patch system to repair surgically created spina bifida in a sheep model for its efficacy in healing the skin defect, protecting the underlying spinal cord and reducing the Chiari II malformation. Spina bifida was created surgically in 16 fetuses from eight timed-pregnant sheep at gestational age of 75 days. Two fetuses did not survive the procedure. Repeat hysterotomy was performed at 95 days' gestation to cover the defect with either biocellulose film with underwater adhesive (BCF-adhesive) (n = 7) or human umbilical cord with suture (HUC-suture) (n = 7). Three fetuses without formation of the defect served as reference controls. The skin healing was examined by direct visualization after a planned Cesarean section at term, followed by histological analysis using hematoxylin and eosin and Masson's trichrome stains. Mid-sagittal sections of the fetal cranium and upper cervical spine were analyzed by a pediatric neuroradiologist who was blinded to the type of patch received. Three fetuses that received the BCF-adhesive and six fetuses that received the HUC-suture survived to term for final analysis. As a result of dislodgment of the BCF-adhesive, all spina bifida defects repaired using BCF-adhesive were not healed and showed exposed spinal cord with leakage of cerebrospinal fluid. In contrast, all spinal defects repaired by HUC-suture were healed with complete regrowth of epidermal, dermal and subdermal tissue components, with no exposed spinal cord. The maximal skin wound width was 21 ± 3.6 mm in the BCF-adhesive group but 3 ± 0.8 mm in the HUC-suture group (P bifida. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  10. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

    Science.gov (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  11. CD133(+) human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis.

    Science.gov (United States)

    Elkhafif, Nagwa; El Baz, Hanan; Hammam, Olfat; Hassan, Salwa; Salah, Faten; Mansour, Wafaa; Mansy, Soheir; Yehia, Hoda; Zaki, Ahmed; Magdy, Ranya

    2011-01-01

    The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133(+) cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133(+) human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133(+) cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.

  12. Identification of a novel population of human cord blood cells with hematopoietic and chondrocytic potential

    Institute of Scientific and Technical Information of China (English)

    Karen E JAY; Anne ROULEAU; T Michael UNDERHILL; Mickie BHATIA

    2004-01-01

    With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin-CD45- cells also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin-CD45-CD34- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin-CD45-CD34- differentiation into chondrocytes.Moreover, unlike CD34+ human hematopoietic stem cells, Lin-CD45-CD34- cells were unable to proliferate or survive in liquid cultures, whereas single Lin-CD45-CD34- cells were able to chimerize the inner cell mass (ICM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin-CD45-CD34-cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.

  13. Generation of induced pluripotent stem cells with high efficiency from human umbilical cord blood mononuclear cells.

    Science.gov (United States)

    Wang, Juan; Gu, Qi; Hao, Jie; Bai, Donghui; Liu, Lei; Zhao, Xiaoyang; Liu, Zhonghua; Wang, Liu; Zhou, Qi

    2013-10-01

    Human induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine. Generating iPSCs from immunologically immature newborn umbilical cord blood mononuclear cells (UCBMCs) is of great significance. Here we report generation of human iPSCs with great efficiency from UCBMCs using a dox-inducible lentiviral system carrying four Yamanaka factors. We generated these cells by optimizing the existing iPSC induction protocol. The UCBMC-derived iPSCs (UCB-iPSCs) have characteristics that are identical to pluripotent human embryonic stem cells (hESCs). This study highlights the use of UCBMCs to generate highly functional human iPSCs that could accelerate the development of cell-based regenerative therapy for patients suffering from various diseases.

  14. Vascular distribution patterns in monochorionic twin placentas.

    Science.gov (United States)

    De Paepe, M E; DeKoninck, P; Friedman, R M

    2005-07-01

    Several recent publications have focused on the association between the occurrence of twin-to-twin transfusion syndrome (TTTS) in diamniotic-monochorionic twins and the presence of a number of selected anatomic placental characteristics (distribution of vascular territory, cord insertion, type and number of inter-twin anastomoses). In contrast, the potential importance of the vascular distribution patterns of the individual twins remains to be elucidated. Based on its gross architectural distribution pattern, chorionic vasculature is traditionally described as disperse, magistral or mixed. The aim of this study was (1) to determine the relative prevalence of these vascular distribution patterns in monochorionic twin placentas, and (2) to correlate these patterns with the presence of TTTS and known anatomic placental features linked to TTTS. The placentas of 89 consecutive diamniotic-monochorionic twins (15 with TTTS, 74 without TTTS), examined at Women and Infants Hospital, were studied. Disperse vascular patterns were seen in 53% of twins, and magistral or mixed patterns in 47%. The prevalence of magistral/mixed vascular patterns was significantly higher in TTTS gestations than in non-TTTS gestations (60% versus 44%, Ppatterns and marginal/velamentous cord insertion, low number of inter-twin anastomoses, and uneven distribution of the vascular territories. These findings suggest that the magistral/mixed vascular distribution pattern may represent an important placental architectural feature contributing to the complex pathophysiology of TTTS.

  15. Human umbilical cord blood-derived mesenchymal stem cells promote regeneration of crush-injured rat sciatic nerves

    Institute of Scientific and Technical Information of China (English)

    Mi-Ae Sung; Jong-Ho Lee; Hun Jong Jung; Jung-Woo Lee; Jin-Yong Lee; Kang-Mi Pang; Sang Bae Yoo; Mohammad S. Alrashdan; Soung-Min Kim; Jeong Won Jahng

    2012-01-01

    Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells (1 × 106) or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchymal stem cells promote the functional recovery of crush-injured sciatic nerves.

  16. Gene expression analysis of the microdissected trophoblast layer of human placenta after the spontaneous onset of labor

    National Research Council Canada - National Science Library

    Kim, Soo Hyun; Shim, Sung Han; Sung, Se Ra; Lee, Kyung A; Shim, Jung Yun; Cha, Dong Hyun; Lee, Kyoung Jin

    2013-01-01

    Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown...

  17. Quantification of viral genome in cord blood donors by real time PCR to investigate human herpesvirus type 8 active infection.

    Science.gov (United States)

    Golchin, Neda; Kheirandish, Maryam; Sharifi, Zohreh; Samiee, Shahram; Kokhaei, Parviz; Pourpak, Zahra

    2015-12-01

    Umbilical cord blood (UCB) is one of the most important sources of hematopoietic stem cells which can be used for transplantation. The transplanted CB stem cells might cause infections in recipients. The aim of this study is to evaluate Human Herpes Virus8 (HHV8) as a Rhadinovirus among CB samples in order to assess safety of cord blood stem cells transplantation. To assess this aim, we surveyed 800 cord blood specimens by Real Time PCR.The overall HHV8 incidence in cord blood mononuclear cells was 1.38% and none of them was in lytic phase of HHV8. The authors suggest further HHV8 study on CB samples for transplantation.

  18. Expression of neurotrimin in the normal and injured adult human spinal cord.

    Science.gov (United States)

    Grijalva, I; Li, X; Marcillo, A; Salzer, J L; Levi, A D

    2006-05-01

    Neurotrimin (Ntm) is a member of the family of neural cell adhesion molecules. Its expression pattern suggests that Ntm promotes axonal fasciculation, guides nerve fibers to specific targets and stabilizes synapses as it accumulates coincident with synaptogenesis. Strong labeling of Ntm was observed in motor and sensory areas of the postnatal rat cortex. It is not known whether Ntm is present in adult human spinal cord (SC). In the present study, a monoclonal antibody specific for Ntm (1B1), is applied to the first study of the expression of Ntm in normal and injured adult human SC. (1) To investigate the expression pattern of Ntm in adult normal human SC, and (2) to observe the changes of Ntm expression after SC injury and compare the differences between normal and injured adult human SC. Human SC tissue was obtained from necropsies of patients with (n=5) and without (n=4) SC injury. The 1B1 Ntm monoclonal antibody was used for immunohistochemical staining on paraffin embedded sections with an ABC kit. (1) In total, 12 slides were analyzed for each group from both cervical and thoracic levels. Motor neurons and Clarke's neurons and glial-like cells were mild to moderately positive in all uninjured SC specimens. (2) In injured SC, no staining was observed in the injury epicenter between two and three levels proximally and distally, but was detected five levels away. (3) In patients older than 67 years of age, Ntm-positive inclusions were present in the white matter of the SC with or without injury. (4) Some meningeal cells were strongly Ntm-positive, especially in the uninjured human SC. Ntm is expressed by motor and Clarke's neurons and glial cells in uninjured human SC. The downregulation of Ntm in the injured SC suggests that its expression is regulated by afferent input. Spinal Cord (2006) 44, 275-279. doi:10.1038/sj.sc.3101840; published online 20 September 2005.

  19. The effects of labor on differential gene expression in parturient women, placentas, and fetuses at term pregnancy

    Directory of Open Access Journals (Sweden)

    Hsiu-Huei Peng

    2011-11-01

    Full Text Available Labor and its associated pain are thought to have unique impacts on parturient women. The goal of this study was to investigate the effects of labor and associated pain on differential gene expression profiles in the maternal, fetal, and placental compartments. We used microarrays to analyze maternal blood (MB, fetal cord blood (CB, and placental tissue samples in pregnant women after term vaginal deliveries (laboring group and in term pregnant women after scheduled Ceasarean sections (nonlaboring group. The upregulated genes in the MB of the laboring group are involved in cytokine and nuclear factor-kappa B signaling pathways, regulation of the networks of toll-like receptor 4, and suppressor of cytokine signaling 3. Upregulated genes in the CB of the laboring group are involved in responding to stress and stimuli by regulating the network genes of the T-cell receptor beta locus and the FK506 binding protein 8. Differentially expressed genes in the placenta of the laboring group are involved in nitric oxide transport, gas transport, response to hydrostatic pressure, oxygen transport, acute phase responses, and the tumor necrosis factor-mediated signaling pathway, which are important during the transient hypoxemia and hypoperfusion that occur in the placenta during uterine contractions. Interestingly, few of the genes exhibited simultaneous changes in all three compartments, indicating that different pathways and complex interactions may be involved in human labor. In conclusion, human labor and its associated pain elicit unique gene regulatory changes in MB, placenta, and CB.

  20. Establishment and validation of microbial limit test for human placenta tablet%人胎盘片微生物限度检查方法的建立及验证

    Institute of Scientific and Technical Information of China (English)

    李静; 王芙

    2015-01-01

    目的:建立人胎盘片微生物限度检查方法并进行验证。方法按照《中国药典》2010年版一部微生物限度检查方法的要求进行验证。结果可用常规法检查人胎盘片的细菌数、霉菌、酵母菌和控制菌,并能符合微生物限度的要求。结论该方法简单快捷、准确可行,可用于人胎盘片的微生物限度检查,有效控制人胎盘片的质量。%Objective To establish and validate microbial limit test for human placenta tablet.Methods The validation was carried out based on requirement about microbial limit test published in《Chinese Pharmacopoeia》2010 edition, con-ducted three independent parallel tests and measured recovery rates.Results The bacterium, molds, yeasts and control bacteria could be examined in human placenta tablet by a conventional method, and the tested results met with the require-ment of microbial limit.Conclusion The method is a simple, fast, accurate and applicable, which could be used in the microbial limit test and effective control of the quality for human placenta tablet.

  1. Hypoxia-inducible factor-2 alpha promotes the proliferation of human placenta-derived mesenchymal stem cells through the MAPK/ERK signaling pathway

    Science.gov (United States)

    Zhu, Chengxing; Yu, Jiong; Pan, Qiaoling; Yang, Jinfeng; Hao, Guangshu; Wang, Yingjie; Li, Lanjuan; Cao, Hongcui

    2016-01-01

    Human placenta-derived mesenchymal stem cells (hPMSCs) reside in a physiologically low-oxygen microenvironment. Hypoxia influences a variety of stem cell cellular activities, frequently involving hypoxia-inducible factor-2 alpha (HIF-2α). This research showed that hPMSCs cultured in hypoxic conditions (5% O2) exhibited a more naïve morphology and had a higher proliferative capability and higher HIF-2α expression than hPMSCs cultured in normoxic conditions (21% O2). Similar to the hypoxic cultures, hPMSCs over-expressing HIF-2α showed higher proliferative potential and higher expression of CCND1 (CyclinD1), MYC (c-Myc), POU5F1 (Oct4) and the components of the MAPK/ERK pathway. In contrast, these genes were down-regulated in the HIF-2α-silenced hPMSCs. After adding the MAPK/ERK inhibitor PD0325901, cell growth and the expression of CCND1 and MYC were inhibited. Furthermore, the chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) showed that HIF-2α bound to the MAPK3 (ERK1) promoter, indicative of its direct regulation of MAPK/ERK components at the transcriptional level during hPMSC expansion. Taken together, our results suggest that HIF-2α facilitated the preservation of hPMSC stemness and promoted their proliferation by regulating CCND1 and MYC through the MAPK/ERK signaling pathway. PMID:27765951

  2. Ultrasonography evaluations of placenta previa

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Seo; Yim, Neung Jae; Oh, Eun Ock [Korea General Hospital, Seoul (Korea, Republic of); Park, Soo Soung [Chung Ang University College of Medicine, Seoul (Korea, Republic of)

    1984-12-15

    Diagnostic ultrasound has become one of the most useful tools in the practice of obstetrics. It has been of particular utility in the placental localization. We analyzed 34 patients of placenta previa scanned by ultrasound. The results were as follows; 1. The age of patient ranged from 22 to 39 years, showing the highest incidence in 26 to 30 years. 2. The accuracy of correct localization was 70.6%. 3. Among 13 cases diagnosed by ultrasound as total placenta previa, 2 cases were partial placental previa and 1 was low-lying placenta at the time of delivery. 4. Among 9 cases diagnosed by ultrasound as partial placenta previa, 1 case was total placenta previa and 1 case was low-lying placenta and 1 case was upper segment placenta. 5. Among 10 cases diagnosed by ultrasound as low-lying placenta, 2 cases were partial placenta previa. 6. Among 2 cases diagnosed by ultrasound as upper segment placenta, 1 case was total placenta previa and 1 case was partial placenta previa. 7. Among 9 cases done serial ultrasound, 3 cases revealed that the placenta migrates toward fundus in the course of pregnancy. Therefore, the placental scanning should be repeated in the last month before term to decide the mode of delivery. Conclusively, ultrasonography is the imaging modality of choice in the evaluation of placenta localization because it provides speedy and repeatable way without any known risk to both mother and fetus itself. Careful performance and accurate interpretation should be needed for more correct placental localization.

  3. Surgical Treatment of a Patient with Human Tail and Multiple Abnormalities of the Spinal Cord and Column

    Directory of Open Access Journals (Sweden)

    Chunquan Cai

    2011-01-01

    Full Text Available The dorsal cutaneous appendage, or so-called human tail, is often considered to be a cutaneous marker of underlying occult dysraphism. The authors present a case of human tail occurring in a 9-month-old infant with multiple abnormalities of the spinal cord and spine. Examination revealed unremarkable except for a caudal appendage and a dark pigmentation area in the low back. Neuroradiological scans revealed cleft vertebrae and bifid ribbon, split cord malformations, block vertebrae, and hemivertebra. Surgical excision of the tail and untethering the spinal cord by removal of the septum were performed. The infant had an uneventful postoperative period and was unchanged neurologically for 18 months of followup. To our knowledge, no similar case reports exist in the literature. The specific features in a rare case with a human tail treated surgically are discussed in light of the available literature.

  4. Gene Expression Analysis of the Microdissected Trophoblast Layer of Human Placenta after the Spontaneous Onset of Labor: e77648

    National Research Council Canada - National Science Library

    Soo Hyun Kim; Sung Han Shim; Se Ra Sung; Kyung A Lee; Jung Yun Shim; Dong Hyun Cha; Kyoung Jin Lee

    2013-01-01

      Background Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor...

  5. Culture of multipotent cells isolated from human term placenta%胎盘多分化潜能细胞的体外分离培养

    Institute of Scientific and Technical Information of China (English)

    王玲; 徐秋岚; 苗宗宁; 祝建中; 黄伟

    2007-01-01

    胞密度增大,彼此相连;11~14 d,生长曲线逐渐进入平台期,MSCs铺满瓶底,细胞扩增趋缓,原代培养结束.③β-HCG测定结果:两个时间点培养上清液中均未检测到β-HCG表达.④多分化潜能细胞的表面抗原特性:多分化潜能细胞表达CD29,CD44和CD105,不表达CD34,CD45,CD19和CD106.⑤多分化潜能细胞的诱导分化结果:向神经细胞诱导24 h后,细胞形态明显改变,胞体回缩,胞核部分折光性增强,出现类似于树突及轴突样结构,染色可见神经元特异性烯醇化酶、胶质纤维酸性蛋白阳性.结论:胎盘组织中含有的多分化潜能细胞与骨髓间充质干细胞形态功能相似,胎盘可以作为获取间充质干细胞的一种有效来源.%BACKGROUND: Some researches suggest that placenta is regarded as a new source of mesemchymal stem cells (MSCs). Adherent cells derived from placenta tissue have similar morphological characteristics and surface markers to MSCs; meanwhile, they can differentiate into osteoblasts and nerve cells.OBJECTIVE: To find a new source and way for MSCs separation.DESIGN: Observational study.SETTING: The Third People's Hospital of Wuxi.MATERIALS: Placenta was sourced from cesarean in our department of obstetrics and gynecology and provided confirmed consent from the relatives and ethics committee. The main reagents contained culture medium, sABC kit, DAB staining kit, caprine-anti-rat FITC, recombinant human basic fibroblast growth factor (rh-bFGF), rabbit-anti-human glial fibriliary acidic protein (GFAP).METHODS: The experiment was carried out in the Laboratory of Cells & Molecular Biology, the Third People's Hospital of Wuxi from May 2005 to August 2006. Placenta entity tissue was digested, adherent cells were cultured, morphological characteristics were observed, and growth curves of placenta-derived multipotent cells (PDMCs) in various generations were drawn. On the 1st and 7th days, supernatant was derived from cells in primary culture to measure content of

  6. Cryopreservation of human vascular umbilical cord cells under good manufacturing practice conditions for future cell banks

    Directory of Open Access Journals (Sweden)

    Polchow Bianca

    2012-05-01

    Full Text Available Abstract Background In vitro fabricated tissue engineered vascular constructs could provide an alternative to conventional substitutes. A crucial factor for tissue engineering of vascular constructs is an appropriate cell source. Vascular cells from the human umbilical cord can be directly isolated and cryopreserved until needed. Currently no cell bank for human vascular cells is available. Therefore, the establishment of a future human vascular cell bank conforming to good manufacturing practice (GMP conditions is desirable for therapeutic applications such as tissue engineered cardiovascular constructs. Materials and methods A fundamental step was the adaption of conventional research and development starting materials to GMP compliant starting materials. Human umbilical cord artery derived cells (HUCAC and human umbilical vein endothelial cells (HUVEC were isolated, cultivated, cryopreserved (short- and long-term directly after primary culture and recultivated subsequently. Cell viability, expression of cellular markers and proliferation potential of fresh and cryopreserved cells were studied using trypan blue staining, flow cytometry analysis, immunofluorescence staining and proliferation assays. Statistical analyses were performed using Student’s t-test. Results Sufficient numbers of isolated cells with acceptable viabilities and homogenous expression of cellular markers confirmed that the isolation procedure was successful using GMP compliant starting materials. The influence of cryopreservation was marginal, because cryopreserved cells mostly maintain phenotypic and functional characteristics similar to those of fresh cells. Phenotypic studies revealed that fresh cultivated and cryopreserved HUCAC were positive for alpha smooth muscle actin, CD90, CD105, CD73, CD29, CD44, CD166 and negative for smoothelin. HUVEC expressed CD31, CD146, CD105 and CD144 but not alpha smooth muscle actin. Functional analysis demonstrated acceptable

  7. Conversion of mononuclear cells from human umbilical cord blood into hepatocyte-like cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fang-ting; FANG Jia-zhi; YU Jie; WAN Hui-juan; YE Jing; LONG Xia; YIN Mei-jun; HUANG Chun-qiao

    2006-01-01

    Objective:To evaluate the differentiation of human umbilical cord blood cells into hepatocyte-like cells. Methods: Mononuclear cells (MNCs) derived from human umbilical cord blood were isolated using Ficoll. The experiment was derived into 3 categories: (1) MNCs co-cultured with 50 mg minced liver tissue separated by a trans-well membrane and then collected at 0 h,24 h,48 h and 72 h; (2) MNCs cultured along supplemented with 100 ml/L FBS, 100 μ/ml penicillin, 100 μg/ml streptomycin, 4. 7 μg/ml linoleic acid, 1×ITS, 10-4 mol/L L-Ascorbic acid 2-P and a combination of FGF4 (100 ng/ml) and HGF (20 ng/Ml). Cells were then collected at 0 d and 16 d to examine the expression profile of hepatocyte correlating markers; (3) 0.2-0.3 ml of MNCs with a cell density of 2×107/ml were transplanted into prepared recipient mice [n= 12, injected with 0.4 ml/kg (20%) CCl4 and 150 ng/kg 5-fluorouracil (5-Fu) prior the transplant 24 h and 48 h, respectively] via injection through tail vein. Mice were sacrificed 4 weeks after transplantation. The hepatocyte correlating mRNAs and proteins were determined by RTPCR, immunohistochemical analysis and immunoflurence technique. Results: (1) After 72 h, a number of glycogen positive stained cells were observed with MNCs co-cultured with damaged mouse liver tissues.The expression of hepatocyte markers, human albumin (ALB), α-fetal protein (AFP) and human GATA4 Mrna and proteins were detected by RT-PCR and immunohistochemistry as well. For the confirmation,the DNA sequencing of PCR products was performed. In control groups, MNCs co-cultured with normal mouse hepatocytes or MNCs cultured alone, all markers remained negative. (2) In growth factor supplemented culture system, MNCs developed into larger volume with richer cytoplasm and binucleation after 16 d. Positive expression of ALB, AFP, CK18 and CK19 Mrna were detected with RT-PCR, and ALB positive staining was observed by immunocytochemistry as well. In contrast, MNCs cultured without

  8. Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer's Disease-Like Murine Model.

    Science.gov (United States)

    Ehrhart, Jared; Darlington, Donna; Kuzmin-Nichols, Nicole; Sanberg, Cyndy D; Sawmiller, Darrell R; Sanberg, Paul R; Tan, Jun

    2016-01-01

    Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or adult stem cells, have emerged as effective and relatively safe immunomodulators and neuroprotectors, reducing behavioral impairment in animal models of Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and stroke. In this report, we followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and nontransgenic Sprague-Dawley rats. HUCBCs were injected into tail veins of mice or rats at a single dose of 1 × 10(6) or 2.2 × 10(6) cells, respectively, prior to harvesting of tissues at 24 h, 7 days, and 30 days after injection. For determination of HUCBC distribution, tissues from both species were subjected to total DNA isolation and polymerase chain reaction (PCR) amplification of the gene for human glycerol-3-phosphate dehydrogenase. Our results show a relatively similar biodistribution and retention of HUCBCs in both mouse and rat organs. HUCBCs were broadly detected both in the brain and several peripheral organs, including the liver, kidney, and bone marrow, of both species, starting within 7 days and continuing up to 30 days posttransplantation. No HUCBCs were recovered in the peripheral circulation, even at 24 h posttransplantation. Therefore, HUCBCs reach several tissues including the brain following a single intravenous treatment, suggesting that this route can be a viable method of administration of these cells for the treatment of neurodegenerative diseases.

  9. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease.

    Science.gov (United States)

    Xiong, N; Zhang, Z; Huang, J; Chen, C; Zhang, Z; Jia, M; Xiong, J; Liu, X; Wang, F; Cao, X; Liang, Z; Sun, S; Lin, Z; Wang, T

    2011-04-01

    The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for transplantation-based treatments of Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery of human vascular endothelial growth factor 165 (VEGF 165) conferred molecular protection to the dopaminergic system. As both VEGF and HUMSCs displayed limited neuroprotection, in this study we investigated whether HUMSCs combined with VEGF expression could offer enhanced neuroprotection. HUMSCs were modified by adenovirus-mediated VEGF gene transfer, and subsequently transplanted into rotenone-lesioned striatum of hemiparkinsonian rats. As a result, HUMSCs differentiated into dopaminergic neuron-like cells on the basis of neuron-specific enolase (NSE) (neuronal marker), glial fibrillary acidic protein (GFAP) (astrocyte marker), nestin (neural stem cell marker) and tyrosine hydroxylase (TH) (dopaminergic marker) expression. Further, VEGF expression significantly enhanced the dopaminergic differentiation of HUMSCs in vivo. HUMSC transplantation ameliorated apomorphine-evoked rotations and reduced the loss of dopaminergic neurons in the lesioned substantia nigra (SNc), which was enhanced significantly by VEGF expression in HUMSCs. These findings present the suitability of HUMSC as a vector for gene therapy and suggest that stem cell engineering with VEGF may improve the transplantation strategy for the treatment of PD.

  10. Human umbilical cord-derived mesenchymal stem cells can secrete insulin in vitro and in vivo.

    Science.gov (United States)

    Boroujeni, Zahra Niki; Aleyasin, Ahmad

    2014-01-01

    Diabetes mellitus is characterized by autoimmune destruction of pancreatic beta cells, leading to decreased insulin production. Differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells offers novel ways of diabetes treatment. MSCs can be isolated from the human umbilical cord tissue and differentiate into insulin-secreting cells. Human umbilical cord-derived stem cells (hUDSCs) were obtained after birth, selected by plastic adhesion, and characterized by flow cytometric analysis. hUDSCs were transduced with nonintegrated lentivirus harboring PDX1 (nonintegrated LV-PDX1) and was cultured in differentiation medium in 21 days. Pancreatic duodenum homeobox protein-1 (PDX1) is a transcription factor in pancreatic development. Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT-PCR (P insulin proteins were shown by immunocytochemistry analysis. Insulin secretion of hUDSCs(PDX1+) in the high-glucose medium was 1.8 μU/mL. They were used for treatment of diabetic rats and could decrease the blood glucose level from 400 mg/dL to a normal level in 4 days. In conclusion, our results demonstrated that hUDSCs are able to differentiate into insulin-producing cells by transduction with nonintegrated LV-PDX1. These hUDSCs(PDX1+) have the potential to be used as a viable resource in cell-based gene therapy of type 1 diabetes.

  11. Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury.

    Science.gov (United States)

    Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J; Wright, Megan C; Lepore, Angelo C

    2015-09-01

    Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor

  12. Critical closing pressure in the fetal vessel of the human placenta in vitro. II. Compared effects of a beta adrenergic substance, Salbutamol, on the critical closing pressure and vascular resistance.

    Science.gov (United States)

    Benedetti, W L; González-Panizza, V H; Alvarez, H

    1976-01-01

    Salbutamol effects upon the fetal vessels of the human placenta were studied in vitro, comparing the changes induced upon the critical closing pressure (CCP) and viscous resistance (R). Four normal full-term placentas were used. In each of them, 4 cotyledonary areas were perfused, thus obtaining a total of 16 measurements for the observation of spontaneous variations (blank), by perfusion with Krebs solution, and the same amount for the variations due to Salbutamol. The concentration used was 10 microgram/ml, with a 4.25 ml/min flow. The relative effect of Salbutamol upon CCP was its decrease--30.4% against a relative spontaneous variation of --3.6%. The mean relative effect upon R was much lower, --9.4%. against a mean relative spontaneous variation of + 3.3%. The advantages of using CCP instead of R as a parameter of vascular contractility are discussed. Furthermore, Salbutamol is suggested to be useful in improving fetal placental circulation.

  13. Human mesenchymal cells from adipose tissue deposit laminin and promote regeneration of injured spinal cord in rats.

    Science.gov (United States)

    Menezes, Karla; Nascimento, Marcos Assis; Gonçalves, Juliana Pena; Cruz, Aline Silva; Lopes, Daiana Vieira; Curzio, Bianca; Bonamino, Martin; de Menezes, João Ricardo Lacerda; Borojevic, Radovan; Rossi, Maria Isabel Doria; Coelho-Sampaio, Tatiana

    2014-01-01

    Cell therapy is a promising strategy to pursue the unmet need for treatment of spinal cord injury (SCI). Although several studies have shown that adult mesenchymal cells contribute to improve the outcomes of SCI, a description of the pro-regenerative events triggered by these cells is still lacking. Here we investigated the regenerative properties of human adipose tissue derived stromal cells (hADSCs) in a rat model of spinal cord compression. Cells were delivered directly into the spinal parenchyma immediately after injury. Human ADSCs promoted functional recovery, tissue preservation, and axonal regeneration. Analysis of the cord tissue showed an abundant deposition of laminin of human origin at the lesion site and spinal midline; the appearance of cell clusters composed of neural precursors in the areas of laminin deposition, and the appearance of blood vessels with separated basement membranes along the spinal axis. These effects were also observed after injection of hADSCs into non-injured spinal cord. Considering that laminin is a well-known inducer of axonal growth, as well a component of the extracellular matrix associated to neural progenitors, we propose that it can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury.

  14. Identificação de Listeria monocytogenes em placentas humanas e espécimes de aborto pela técnica de imunoistoquímica Identification of Listeria monocytogenes in human placentas and abortion species through immunohistochemical technique

    Directory of Open Access Journals (Sweden)

    Jussara Pires Schwab

    2003-06-01

    Full Text Available A listeriose é causada por um microrganismo que se encontra amplamente disseminado na natureza e tem sido isolado do solo, de fezes humanas e de animais e pode, eventualmente, contaminar os alimentos. A Listeria monocytogenes é patogênica para o homem e tornou-se o principal patógeno nas doenças transmitidas pelos alimentos. Tendo-se em vista que a incidência de listeriose humana não é bem conhecida e as placentites possuem aspecto morfológico inespecífico e não são, muitas vezes, investigadas para este fator etiológico, surgiu a motivação para desenvolver a técnica de imunoistoquímica para o diagnóstico de Listeria monocytogenes em placentas ou produtos de aborto, utilizando um anticorpo policlonal anti-Listeria (Biodesign®. Um projeto-piloto foi realizado a partir do material encontrado em dez placentas provenientes de abortos ou partos prematuros ocorridos no ano de 2000 no Hospital de Clínicas de Porto Alegre (HCPA. As lâminas foram analisadas através do exame microscópico convencional (HE e de imunoistoquímica (IHQ. Os resultados deste projeto revelaram a presença de Listeria monocytogenes em cinco dos dez (50% casos estudados. Todos os casos apresentaram alterações sugestivas de processo inflamatório agudo supurativo. Frente a estes achados torna-se importante considerar a infecção por Listeria monocytogenes detectável por IHQ como um elemento no diagnóstico da patogenia do aborto ou das infecções perinatais, podendo este achado contribuir para o tratamento dos recém-nascidos ou das parturientes. As características microscópicas de listeriose na placenta, embora não-patognomônicas, permitem ao patologista um diagnóstico presuntivo, e a confirmação pode ser realizada pelo método de imunoistoquímica.Listeria monocytogenes, a food-borne, human-infecting pathogen, is widespread in nature and has been isolated from soil, human and animal feces. Since the incidence of human listeriosis is not well

  15. High-resolution multi-parametric quantitative magnetic resonance imaging of the human cervical spinal cord at 7T.

    Science.gov (United States)

    Massire, Aurélien; Taso, Manuel; Besson, Pierre; Guye, Maxime; Ranjeva, Jean-Philippe; Callot, Virginie

    2016-12-01

    Quantitative MRI techniques have the potential to characterize spinal cord tissue impairments occurring in various pathologies, from both microstructural and functional perspectives. By enabling very high image resolution and enhanced tissue contrast, ultra-high field imaging may offer further opportunities for such characterization. In this study, a multi-parametric high-resolution quantitative MRI protocol is proposed to characterize in vivo the human cervical spinal cord at 7T. Multi-parametric quantitative MRI acquizitions including T1, T2(*) relaxometry mapping and axial diffusion MRI were performed on ten healthy volunteers with a whole-body 7T system using a commercial prototype coil-array dedicated to cervical spinal cord imaging. Automatic cord segmentation and multi-parametric data registration to spinal cord templates enabled robust regional studies within atlas-based WM tracts and GM horns at the C3 cervical level. T1 value, cross-sectional area and GM/WM ratio evolutions along the cervical cord were also reported. An original correction method for B1(+)-biased T1 mapping sequence was additionally proposed and validated on phantom. As a result, relaxometry and diffusion parameters derived from high-resolution quantitative MRI acquizitions were reported at 7T for the first time. Obtained images, with unmatched resolutions compared to lower field investigations, provided exquisite anatomical details and clear delineation of the spinal cord substructures within an acquisition time of 30min, compatible with clinical investigations. Regional statistically significant differences were highlighted between WM and GM based on T1 and T2* maps (pquantitative MRI is feasible and lays the groundwork for future clinical investigations of degenerative spinal cord pathologies. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From Bench to Small and Large Animal Myocardial Ischemia Studies.

    Science.gov (United States)

    Liu, Yuan-Hung; Peng, Kai-Yen; Chiu, Yu-Wei; Ho, Yi-Lwun; Wang, Yao-Horng; Shun, Chia-Tung; Huang, Shih-Yun; Lin, Yi-Shuan; de Vries, Antoine A F; Pijnappels, Daniël A; Lee, Nan-Ting; Yen, B Linju; Yen, Men-Luh

    2015-01-01

    Cardiovascular disease is the leading cause of death globally, and stem cell therapy remains one of the most promising strategies for regeneration or repair of the damaged heart. We report that human placenta-derived multipotent cells (hPDMCs) can modulate cardiac injury in small and large animal models of myocardial ischemia (MI) and elucidate the mechanisms involved. We found that hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with mouse neonatal cardiomyocytes. Moreover, hPDMCs exert strong proangiogenic responses in vitro toward human endothelial cells mediated by secretion of hepatocyte growth factor, growth-regulated oncogene-α, and interleukin-8. To test the in vivo relevance of these results, small and large animal models of acute MI were induced in mice and minipigs, respectively, by permanent left anterior descending (LAD) artery ligation, followed by hPDMC or culture medium-only implantation with follow-up for up to 8 weeks. Transplantation of hPDMCs into mouse heart post-acute MI induction improved left ventricular function, with significantly enhanced vascularity in the cell-treated group. Furthermore, in minipigs post-acute MI induction, hPDMC transplantation significantly improved myocardial contractility compared to the control group (p = 0.016) at 8 weeks postinjury. In addition, tissue analysis confirmed that hPDMC transplantation induced increased vascularity, cardiomyogenic differentiation, and antiapoptotic effects. Our findings offer evidence that hPDMCs can modulate cardiac injury in both small and large animal models, possibly through proangiogenesis, cardiomyogenesis, and suppression of cardiomyocyte apoptosis. Our study offers mechanistic insights and preclinical evidence on using hPDMCs as a therapeutic strategy to treat severe cardiovascular diseases.

  17. Effects of nicotine-specific antibodies, Nic311 and Nic-IgG, on the transfer of nicotine across the human placenta.

    Science.gov (United States)

    Nekhayeva, Ilona A; Nanovskaya, Tatiana N; Pentel, Paul R; Keyler, Dan E; Hankins, Gary D V; Ahmed, Mahmoud S

    2005-11-25

    The adverse effects of smoking during pregnancy on fetal development are, in part, due to nicotine. These effects may be due to the actions of nicotine in fetal circulation or on placental functions. In pregnant rats, vaccination with a nicotine immunogen reduces the transfer of nicotine from the maternal to fetal circulation. However, extrapolation of these results to pregnant women might not be valid due to the well-recognized differences between human and rat placentas. In the current investigation, the effects of nicotine-specific antibodies on the transfer of nicotine from the maternal to fetal circuit of the dually perfused human placental lobule were determined. Two types of nicotine-specific antibodies were investigated; nicotine-specific mouse monoclonal antibody (Nic311, K(d) for nicotine 60nM) and IgG from rabbits vaccinated with a nicotine immunogen (Nic-IgG, K(d) 1.6nM). Transfer of the antibodies from maternal to fetal circuits was negligible. Both rabbit Nic-IgG and, to a lesser extent, mouse monoclonal Nic311 significantly reduced nicotine transfer from the maternal to fetal circuit as well as the retention of the drug by placental tissue. These effects were mediated by a substantial increase in the protein binding of nicotine and a reduction in the unbound nicotine concentration. Therefore, the data cited in this report suggest that the use of nicotine-specific antibodies might reduce fetal exposure to the drug, and that antibody affinity for nicotine is a key determinant of the extent of nicotine transfer.

  18. Establishment of an adherent cell layer from human umbilical cord blood

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    Alfonso Zeni Z.C.

    2000-01-01

    Full Text Available In addition to bone marrow and peripheral blood, stem cells also occur in human umbilical cord blood (HUCB, and there is an increasing interest in the use of this material as an alternative source for bone marrow transplantation and gene therapy. In vitro hematopoiesis has been maintained for up to 16 weeks in HUCB cultures, but the establishment of an adherent, stromal layer has consistently failed. Adherent cell precursors among mononuclear cells from HUCB were sought for in long-term cultures. Mononuclear cells obtained from cord blood after full term, normal deliveries were cultivated at different concentrations in Iscove's modified Dulbecco's medium (IMDM with weekly feeding. An adherent layer was detected in 16 of 30 cultures, 12 of which were plated at cell concentrations higher than 2 x 10(6 cells/ml. In contrast to bone marrow cultures, in which the stroma is detected early, in most (10/16 positive cultures from HUCB the adherent layer was identified only after the fourth week of culture. The cells never reached confluence and detached from the plate approximately four weeks after detection. May-Grünwald-Giemsa staining of positive cultures revealed fibroblast- or endothelial-like adherent cells in an arrangement different from that of bone marrow stroma in 13 samples. In two of these, the adherent cells were organized into characteristic, delimited cords of cells. Unlike bone marrow cultures, fat cells were never observed in the adherent layers. A rapid development of large myeloid cells in the first week of culture was characteristic of negative cultures and these cells were maintained for up to 12 weeks. HUCB contains adherent cell precursors which occur in lower numbers than in bone marrow and may be at a different (possibly less mature stage of differentiation.

  19. Placenta associated pregnancy complications in pregnancies complicated with placenta previa

    National Research Council Canada - National Science Library

    Yael Baumfeld; Reli Herskovitz; Zehavi Bar Niv; Salvatore Andrea Mastrolia; Adi Y. Weintraub

    2017-01-01

    Objectives: The purpose of our study was to examine the hypothesis that pregnancies complicated with placenta previa have an increased risk of placental insufficiency associated pregnancy complications...

  20. Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats

    Institute of Scientific and Technical Information of China (English)

    LIANG Peng; JIN Lian-hong; LIANG Tao; LIU En-zhong; ZHAO Shi-guang

    2006-01-01

    Background Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord.Methods NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n=15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group,NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA.Results NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P< 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P< 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression

  1. Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.

    Science.gov (United States)

    Corbel, T; Gayrard, V; Puel, S; Lacroix, M Z; Berrebi, A; Gil, S; Viguié, C; Toutain, P-L; Picard-Hagen, N

    2014-08-01

    The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G.

  2. Expression and immunolocalisation of the endocytic receptors megalin and cubilin in the human yolk sac and placenta across gestation.

    Science.gov (United States)

    Burke, K A; Jauniaux, E; Burton, G J; Cindrova-Davies, T

    2013-11-01

    Megalin and cubilin are multifunctional endocytic receptors associated with many transporting epithelia. They play an essential role in transport of nutrients through the visceral yolk sac of rodents during embryogenesis. Here, we immunolocalise them to the endodermal layer of the human yolk sac, and to the syncytiotrophoblast and cytotrophoblast cells of placental villi. In villi, the protein level of both receptors increased with gestation. The mRNA for megalin remained constant, while that encoding cubilin increased with gestation. These results suggest megalin and cubilin may be important in human maternal-fetal transfer, and that they increase across gestation to facilitate this function.

  3. Effects of transforming growth factor-beta on long-term human cord blood monocyte cultures

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    Orcel, P.; Bielakoff, J.; De Vernejoul, M.C. (INSERM U18, Hopital Lariboisiere, Paris (France))

    1990-02-01

    Transforming growth factor-beta (TGF-beta) modulates growth and differentiation in many cell types and is abundant in bone matrix. We recently showed that human cord blood monocytes cultured in the presence of 1,25(OH)2D3 acquire some features of osteoclast precursors. Since TGF-beta has been shown to influence bone resorption in organ culture, we have studied the effect of TGF-beta (1-1,000 pg/ml) on cord blood monocyte cultures. These cells were cultured on plastic substrate during 3 weeks in the presence of 20% horse serum and 10(-9) M 1,25(OH)2D3. TGF-beta, from a concentration of 10 pg/ml in the culture medium, decreased in a dose dependent manner the formation of multinucleated cells. At a concentration of TGF-beta of 1 ng/ml, the multinucleated cells were reduced to 2.1% +/- 0.3%, compared to 19.3% +/- 1.5% in control cultures. TGF-beta inhibited in a dose-dependent manner the proliferation of cord blood monocytes as assessed by 3H-thymidine incorporation at 7 and 14 days of culture. The fusion index was also decreased by 3 weeks of treatment with TGF-beta. Indomethacin did not reverse the inhibitory effects of TGF-beta. The expression of the osteoclastic phenotype was assessed using two different antibodies: 23C6, a monoclonal antibody directed against the vitronectin receptor, which is highly expressed by osteoclasts but not by adult monocytes, and an antibody to HLA-DR, which is not present on osteoclast. TGF-beta decreased the expression of HLA-DR and increased in a dose-dependent manner the proportion of 23C6-labeled cells; these results suggest that TGF-beta could modulate a differentiation effect to the osteoclastic phenotype. However, when cord blood monocytes were cultured on devitalized rat calvariae prelabeled with 45Ca, TGF-beta did not induce any 45Ca release from bone cultured with monocytes.

  4. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features.

    Science.gov (United States)

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-06-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.

  5. The proteomic analysis of human neonatal umbilical cord serum by mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Hong-juan SONG; Ping ZHANG; Xue-jiang GUO; Lian-ming LIAO; Zuo-min ZHOU; Jia-hao SHA; Yu-gui CUI; Hui JI; Jia-yin LIU

    2009-01-01

    Aim: To investigate the proteome composition and function of human neonatal arterial umbilical cord.Methods: Serum proteomic analyses were performed on samples from both males and females by using a combination of techniques: (1) removal of six high-abundance proteins, (2) tryptic digestion of low-abundance proteins, (3) separation of peptide mixtures by reverse-phase high-performance liquid chromatography (RP-HPLC), and (4) peptide identification using electrospray ionization tandem mass spectrometry (ESI-MS/MS).Results: A total of 837 non-redundant proteins were identified, with 213 male-specific and 239 female-specific proteins. Among them, 319 proteins were identified by at least 2 distinct peptides. The subcellular localization, function, and pathway involvement for each of the identified proteins were analyzed. A comparison of this neonatal proteome to that of adult serum proteome revealed novel bioma-rkers, such as alpha-fetoprotein and periostin that were specific to newborn infants.Conclusion: These data will contribute to a better understanding of the composition of umbilical cord serum and aid the discovery of novel biomarkers for the prenatal diagnosis of fetal abnormalities.

  6. Few single nucleotide variations in exomes of human cord blood induced pluripotent stem cells.

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    Rui-Jun Su

    Full Text Available The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs reprogrammed from human cord blood (CB CD34(+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2-14% reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS, OS and ZSCAN4 (OSZ, OS and MYC and KLF4 (OSMK. Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs, in exomes, including untranslated regions (UTR, in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking.

  7. Review: Placenta, evolution and lifelong health.

    Science.gov (United States)

    Lewis, R M; Cleal, J K; Hanson, M A

    2012-02-01

    The intrauterine environment has an important influence on lifelong health, and babies who grew poorly in the womb are more likely to develop chronic diseases in later life. Placental function is a major determinant of fetal growth and is therefore also a key influence on lifelong health. The capacity of the placenta to transport nutrients to the fetus and regulate fetal growth is determined by both maternal and fetal signals. The way in which the placenta responds to these signals will have been subject to evolutionary selective pressures. The responses selected are those which increase Darwinian fitness, i.e. reproductive success. This review asks whether in addition to responding to short-term signals, such as a rise in maternal nutrient levels, the placenta also responds to longer-term signals representing the mother's phenotype as a measure of environmental influences across her life course. Understanding how the placenta responds to maternal signals is therefore not only important for promoting optimal fetal growth but can also give insights into how human evolution affected developmental history with long-term effects on health and disease.

  8. Metabolic profile of injured human spinal cord determined using surface microdialysis.

    Science.gov (United States)

    Chen, Suliang; Phang, Isaac; Zoumprouli, Argyro; Papadopoulos, Marios C; Saadoun, Samira

    2016-12-01

    The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self-organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure. A Kohonen map, which is an unsupervised, self-organizing topology-preserving neural network, was used to analyze 3366 h of monitoring data. We first visualized the different spinal cord metabolic states. Our data show that the injured cord assumes one or more of four metabolic states. On the basis of their metabolite profiles, we termed these states near-normal, ischemic, hypermetabolic, and distal. We then visualized how patients' intraspinal pressure and spinal cord perfusion pressure affect spinal cord metabolism. This revealed that for more than 60% of the time, spinal cord metabolism is patient-specific; periods of high intraspinal pressure or low perfusion pressure are not associated with specific spinal cord metabolic patterns. Finally, we determined relationships between spinal cord metabolism and neurological status. Patients with complete deficits have shorter periods of near-normal spinal cord metabolic states (7 ± 4% vs. 58 ± 12%, p injured spinal cord and may thus aid us in treating patients with acute spinal cord injuries.

  9. Expression of DC-SIGN and DC-SIGNRs in placentas of HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Komala Pillay

    2014-09-01

    Full Text Available Background. Human dendritic cell-specific intracellular adhesion molecule-3 (ICAM3-grabbing non-integrin (DC-SIGN is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes. DC-SIGN is highly expressed in placental tissue on dendritic cells and Hofbauer cells, and it is suggested that HIV may become adsorbed to DC-SIGN on Hofbauer cells as part of the mechanism of mother-to-child HIV transmission. A possible mechanism of transfer of the virus from the Hofbauer cells to the fetus is the subsequent adsorption to DC-SIGN-related molecules (DC-SIGNRs, present on immediately adjacent capillary vascular endothelium. However, data on DC-SIGN and DC-SIGNR expression in the placenta are few.Methods. Forty term placentas from HIV-positive mothers and 21 term placentas from HIV-negative mothers underwent immunohistochemistry staining for DC-SIGN and DC-SIGNR expression. Five random sets of 10 villi were assessed, and the average number of positive cells were counted in each case. In addition, where possible, maternal and cord blood viral loads and maternal CD4+ counts were performed in the HIV-positive group only.Results. The median maternal CD4+ count was 377 cells/µl and 27% of participants had undetectable viral loads; the median detectable viral load was 3.72 log. Most (97% of the cord bloods tested in infants from HIV-positive mothers had lower than detectable viral loads. HIV-positive cases had significantly greater expression of both DC-SIGNRs (median values in HIV-positive cases, 14.5 positive cells/10 villi (pc/10villi, compared with 11 pc/10villi in HIV-negative cases, p=0.020 and DC-SIGN (median value in HIV-positive cases, 26.5 pc/10villi, compared with 23 pc/10villi in HIV-negative cases, p=0.037. DC-SIGNR expression was also noted in Hofbauer cells and decidual macrophages in addition to endothelium (reported currently. There was no difference in expression of DC-SIGN and DC-SIGNRs in patients

  10. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    Science.gov (United States)

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs.

  11. Effect in vitro of the Phenobarbital on the Activity of the Enzyme Adenosine Triphosphatase (ATPase of Sodium and Potassium Dependent in Human Placenta. Efecto in vitro del fenobarbital sobre la actividad de la enzima Adenosintrifosfatasa de sodio y potasio dependiente en placenta humana.

    Directory of Open Access Journals (Sweden)

    Pedro Sánchez Frenes

    2007-02-01

    Full Text Available

    Background: Most of the drugs can pass to the fetus through the placenta, conditioning alterations of the development and fetal growth. Objective: To evaluate the effect in vitro of Phenobarbital on the activity of adenosine triphosphatase of sodium and potassium dependent in human placenta. Method: A study in vitro was carried out, in total homogenizes of placentas coming from 30 mothers that were assisted in the Gynecological and Obstetric Educational Provincial Hospital ¨Mariana Grajales¨, in Santa Clara, during the period March-July 1993. Phenobarbital was administered in concentrations of 0,1 mg/ml, 0,15 mg/ml and 0,2 mg/ml, keeping in mind the therapeutic dose to which was prescribed. The analyzed variables were: enzymatic activity and inhibition type. Results: The enzymatic activity of the adenosine triphosphatase of sodium and potassium dependent, diminished in a significant way, proportionally with the diminishment of the administered concentration of Phenobarbital. The inhibitory effect of the drug also turned out to be dependent of the concentration, presenting a major inhibition as the dose was increased. Conclusion: Phenobarbital produced highly significant decrease in the activity of adenosine triphosphatase of sodium and dependent potassium. This inhibition is of competitive type.

    Fundamento: La mayoría de los fármacos, en mayor o menor medida, son capaces de pasar al feto a través de la placenta, condicionando alteraciones del desarrollo y del crecimiento fetal. Objetivo: Evaluar el efecto in vitro del fenobarbital sobre la actividad de la Adenosintrifosfatasa de sodio y potasio dependiente de placenta humana. Método: Se realizó un estudio in vitro, en homogeneizados totales de placentas provenientes de 30 madres que fueron atendidas en el Hospital Provincial Docente Ginecobst

  12. Ultrasound, normal placenta - Braxton Hicks (image)

    Science.gov (United States)

    ... performed at 17 weeks gestation. It shows the placenta during a normal (Braxton Hicks) contraction. Throughout the ... contracts to facilitate better blood flow through the placenta and the fetus. In this ultrasound, the placenta ...

  13. UV-activated 7-dehydrocholesterol-coated titanium implants promote differentiation of human umbilical cord mesenchymal stem cells into osteoblasts.

    Science.gov (United States)

    Satué, María; Ramis, Joana M; Monjo, Marta

    2016-01-01

    Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23℃. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants.

  14. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury:a biomechanical evaluation

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  15. OBSERVATIONS ON VASCULAR PATTERN OF CHORIONIC BLOOD VESSELS OF PLACENTA

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    Yousuf Sarwar

    2013-10-01

    Full Text Available ABSTRACT: BACKGROUND: Placenta is a choriodecidual structure develops during pregnancy implanted on the uterine wall and car ries vital functions. It is connected to the foetus through umbilical cord. The branches of umbilical vessels that traverse along foetal surface of placenta are referred as chorionic vessels. There are two different patterns of chorionic vessels – Dispersa l and Magistral. In the dispersal type, the umbilical vessels undergo successive divisions with gradually diminishing caliber towards periphery while in magistral pattern the vessels traverse to the edge of placenta without appreciable decrease in diameter of vessels. The present study has been done for visualization of the pattern of chorionic vessels in placenta obtained from labour room of a tertiary care hospital in eastern Bihar, India. MATERIALS AND METHODS: A total of one hundred and fifty (150 fres h and intact placenta of full term pregnancies collected from Obstetrics & Gynaecology department were included in the study. After washing with distilled water, removal of blood clots were done with slight digital pressure applied over arteries and vein a nd later on by irrigation with saline. The cut end of the umbilical cord was carefully visualized to identify the umbilical arteries and vein. Dye was injected into umbilical vessels under normal physiological pressure and diameter of chorionic blood vesse ls were taken at the center and periphery. Ultimately each vessel was followed and examined to observe the dispersal and magistral pattern of chorionic blood vessels of placenta. RESULTS AND CONCLUSION: Out of the total of one hundred and fifty (150 full term placenta obtained and examined in the Anatomy department during the study period, 64% Dispersal type & 36 % of Magistral type of arterial pattern of branching of chorionic vessels were observed. Vein and its tributaries presented Dispersal pattern in 60% and Magistral pattern in 40%. There is a significant

  16. In vivo tracking of human placenta derived mesenchymal stem cells in nude mice via 14C-TdR labeling

    OpenAIRE

    2015-01-01

    Background In order to shed light on the regenerative mechanism of mesenchymal stem cells (MSCs) in vivo, the bio-distribution profile of implanted cells using a stable and long-term tracking method is needed. We herein investigated the bio-distribution of human placental deciduas basalis derived MSCs (termed as PDB-MSCs) in nude mice after intravenous injection by carbon radioisotope labeling thymidine (14C-TdR), which is able to incorporate into new DNA strands during cell replication. Resu...

  17. Functional responses in the human spinal cord during willed motor actions: evidence for side- and rate-dependent activity.

    Science.gov (United States)

    Maieron, Marta; Iannetti, Gian Domenico; Bodurka, Jerzy; Tracey, Irene; Bandettini, Peter A; Porro, Carlo A

    2007-04-11

    Although the spinal cord is the output station of the central motor system, little is known about the relationships between its functional activity and willed movement parameters in humans. We investigated here blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) signal changes in the cervical spinal cord during a simple finger-to-thumb opposition task in 13 right-handed volunteers, using a dedicated array of 16 receive-only surface coils on a 3 Tesla MRI system. In a first experiment, we found significant fMRI signal increases on both sides of the lower cervical spinal cord while subjects performed the motor task at a comfortable pace (approximately 0.5 Hz) using either hand. Both the spatial extent of movement-related clusters and peak signal increases were significantly higher on the side of the cord ipsilateral to the moving hand than on the contralateral side. Movement-related activity was consistently larger than signal fluctuations during rest. In a second experiment, we recorded spinal cord responses while the same motor sequence was performed using the dominant hand at two different rates (approximately 0.5 or 1 Hz). The intensity but not the spatial extent of the response was larger during higher rates, and it was higher on the ipsilateral side of the cord. Notwithstanding the limited spatial resolving power of the adopted technique, the present results clearly indicate that the finger movement-related fMRI signals recorded from the spinal cord have a neural origin and that as a result of recent technological advances, fMRI can be used to obtain novel and quantitative physiological information on the activity of spinal circuits.

  18. The Role of Human Adult Peripheral and Umbilical Cord Blood Platelet-Rich Plasma on Proliferation and Migration of Human Skin Fibroblasts.

    Science.gov (United States)

    Hashemi, Seyedeh-Sara; Mahmoodi, Mahdokht; Rafati, Ali Reza; Manafi, Farzad; Mehrabani, Davood

    2017-05-01

    Wound healing is a complex and dynamic process following damage in tissue structures. Due to extensive skin damage caused by burn injuries, this study determined the role of human adult peripheral and umbilical cord blood platelet-rich plasma on proliferation and migration in human skin fibroblasts. Platelet-rich plasma (5, 10, 15, 20 and 50% PRP) from human umbilical cord blood and adult peripheral blood were provided and added to fibroblasts cultured from a human skin sample. Migration and proliferation of fibroblasts were assessed in comparison to 10% FBS and by the fibroblast responses to a concentration gradient. All components of the umbilical cord blood PRP significantly stimulated the growth of fibroblasts when compared to the negative control. Fibroblast growth was enhanced in a dose dependent manner. All fibroblast cultures retained normal morphology. No significant difference was noted between umbilical cord blood and adult peripheral blood PRP preparations regarding cell proliferation and migration, but the difference to 10% FBS was significant. 1% and 50% PRP reduced cellular proliferation. The 20% umbilical cord blood PRP and 10% adult peripheral blood PRP had a significant stimulatory effect on the migration of the skin fibroblast cells in comparison with 10% FBS. As PRP could promote the migration and proliferation of dermal fibroblasts, it can be safely added in cultures when treatment of chronic wounds without triggering the immune response is needed.

  19. Placenta associated pregnancy complications in pregnancies complicated with placenta previa

    Directory of Open Access Journals (Sweden)

    Yael Baumfeld

    2017-06-01

    Conclusions: Our study demonstrated an increased rate of placental insufficiency associated complications in women with placenta previa. This is of clinical relevance and suggests that a careful surveillance for women with placenta previa may help in minimizing maternal, fetal and neonatal complications.

  20. Placenta associated pregnancy complications in pregnancies complicated with placenta previa.

    Science.gov (United States)

    Baumfeld, Yael; Herskovitz, Reli; Niv, Zehavi Bar; Mastrolia, Salvatore Andrea; Weintraub, Adi Y

    2017-06-01

    The purpose of our study was to examine the hypothesis that pregnancies complicated with placenta previa have an increased risk of placental insufficiency associated pregnancy complications (IUGR, preeclampsia, placental abruption and perinatal mortality). Our study included all deliveries that occurred at Soroka University Medical Center (Beer Sheva, Israel) between January 1998 and December 2013. Of them 1,249 were complicated by placenta previa and represented our study group. A composite outcome was created to include conditions associated with placental insufficiency. It included hypertensive disorders (i.e. gestational hypertension, mild and severe preeclampsia, HELLP and eclampsia), small for gestational age neonates and placental abruption. Patients with pregnancy complicated by placenta previa had significantly different obstetrical characteristics including bad obstetric history (8% vs. 4%, p placenta previa had higher rates of vaginal bleeding in the second half of pregnancy (3% vs. 0%, p placenta (4% vs. 0.5%, p placenta previa group (21% vs. 13%, p placenta previa. This is of clinical relevance and suggests that a careful surveillance for women with placenta previa may help in minimizing maternal, fetal and neonatal complications. Copyright © 2017. Published by Elsevier B.V.

  1. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

    Science.gov (United States)

    Zhang, Zheng; Lin, Hu; Shi, Ming; Xu, Ruonan; Fu, Junliang; Lv, Jiyun; Chen, Liming; Lv, Sa; Li, Yuanyuan; Yu, Shuangjie; Geng, Hua; Jin, Lei; Lau, George K K; Wang, Fu-Sheng

    2012-03-01

    Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

  2. Limb oxygenation during the cold pressor test in spinal cord-injured humans.

    Science.gov (United States)

    Ogata, Hisayoshi; Hobara, Hiroaki; Uematsu, Azusa; Ogata, Toru

    2012-04-01

    To investigate changes in tissue oxygenation in the arm and leg during the cold pressor test in humans with spinal cord injury (SCI). Subjects with SCI at cervical 6 (n=7) and subjects with SCI at thoracic 5 or thoracic 6 (n=5) experienced 3-min cold water immersion of the foot and subsequent 10-min recovery. Changes in tissue oxygenation and blood pressure were determined. Tissue oxygenation was assessed by hemoglobin/myoglobin concentration (Hb/MbO2) measured using near-infrared spectroscopy. Mean arterial blood pressures increased significantly by 15±9 and 6±6 mmHg during cold water immersion in the cervical and thoracic SCI groups, respectively (Pcontrol of arm oxygenation and leg oxygenation in the region below SCI.

  3. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

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    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  4. Distinguish on the viability of human umbilical cord mesenchymal stem cells using delayed luminescence

    Science.gov (United States)

    Chen, Ping; Li, Xing; Wang, Yan; Bai, Hua; Lin, Lie

    2014-09-01

    In this paper, we report the discrimination of the viability of human umbilical cord mesenchymal stem cells (hUC-MSCs) with photo-induced delayed luminescence (DL). We measure the DL decay kinetics of hUC-MSCs using an ultraweak luminescence detection system, and find the significant difference in the weight distributions of the decay rate for hUC-MSCs with high and low viabilities. Spectral discrimination of hUC-MSCs with high and low viabilities is thus carried out by comparing the DL kinetics parameters, including the initial intensity, the peak decay rate and the peak weight value. Our results show that the novel optical method for the viability diagnosis of hUC-MSCs has a promising prospect.

  5. Cartilage constructs from human cord blood stem cells seeded in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Koch, Thomas Gadegaard; Foldager, Casper Bindzus

    stimulation. This study demonstrated the chondrogenic potential of human cord blood-derived Multi-Lineage Progenitor Cells (MLPCs) under normoxic and hypoxic culture conditions. Second, MLPCs were seeded in a novel, structurally graded polycaprolactone (SGS-PCL) scaffold and chondrogenesis was evaluated....... MLPCs obtained from BioE Inc (St. Paul, MN, USA) were expanded, and subsequently cultured in a standard micromass pellet system. Pellets were cultured for 21 days in control or chondrogenic induction medium under 5% or 21% oxygen tension. Chondrogenic potential was evaluated by histology (alcian blue......Nano (Aarhus University, Denmark). Micromass pellets cultured in induction medium were larger with a more dense and well-defined spherical structure. GAG production in induced pellets was shown by alcian blue and safranin O staining with most GAG observed centrally in 21%-, and peripherally in 5%-oxygen...

  6. Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

    Directory of Open Access Journals (Sweden)

    Hadar Arien-Zakay

    2010-09-01

    Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

  7. [EXPERIMENTAL STUDY ON HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS-ALGINATE WOUND DRESSING].

    Science.gov (United States)

    Wang, Song; Su, Meilan; Yang, Huachao; Long, Gang; Tang, Zhenrui; Huang, Wen

    2015-09-01

    To observe the growth characteristics of human umbilical cord mesenchymal stem cells (hUCMSCs) cultured on the alginate gel scaffolds and to explore the feasibility of hUCMSCs-alginate dressing for wound healing. hUCMSCs were separated from human umbilical cords and cultured in vitro. After the 4th passage cells were co-cultured with alginate gel (experimental group), the cell growth characteristics were observed under the inverted phase contrast microscope. Vascular endothelial growth factor (VEGF) content was measured and the number of cells was counted at 0, 3, 6, and 9 days after culture; and the cell migration capacity was observed. The hUCMSCs were cultured without alginated gel as control. The model of full-thickness skin defects was established in 32 8-week-old Balb/c male mice and they were randomly divided into 4 groups (n=8): wounds were covered with hUCMSCs-alginate gel compound (MSC-gel group), cell supernatants-alginate gel compound (CS-gel group), 10% FBS-alginate gel compound (FBS-gel group), and 0.01 mol/L PBS-alginate compound (PBS-gel group), respectively. Wound healing rates at 5, 10, and 15 days were observed and calculated; and the wound tissues were harvested for histological and immunohistochemical staining to assess new skin conditions at 15 days after operation. hUCMSCs grew well with grape-like proliferation on the alginate gel, but no cell migration was observed at 7 days after cultivation. VEGF expression and cell number in experimental group were significantly less than those in control group at 3 days (P0.05). hUCMSCs can continuously express VEGF in alginate gel, which is necessary for wound healing. The hUCMSCs-alginate compound is probably a good wound dressing.

  8. EFFECT OF GESTATIONAL DIABETES MELLITUS ON GROSS MORPHOLOGY OF PLACENTA: A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Pankaj Saini

    2015-03-01

    Full Text Available Background: The fetus, placenta and mother constitute a triad of contributors to pregnancy outcome. When pregnancy is complicated by a medical problem like, diabetes mellitus which affects maternal health, architecture and functions of the placenta may even jeopardize the fetal normalcy. The placenta being the bridge between maternal and fetal activities, considered as a window through which maternal dysfunctions and their impacts on fetal well being can be understood. Aim: The aim was to study gross morphology of placentae of women with gestational diabetes mellitus and to compare the results with normal pregnancies. Methods: It was an observational study. After due approval from institutional ethics committee, 40 placentae from pregnant women clinically diagnosed with gestational diabetes mellitus and 40 placentae from uncomplicated normal pregnant women were collected from labour room and operation theatre of department of obstetrics and gynaecology of government medical college hospital in Jaipur (Rajasthan. Confirmed gestational diabetic cases were selected purposively while controls were taken sequentially. Gross morphological features of each placenta were recorded. The statistical methods used were unpaired ‘t’ test and chi square test. Results: The results showed that weight, diameter, surface area, central thickness and number of cotyledons of placentae from diabetic mothers were significantly more than placentae from normal uncomplicated pregnancies, while no significant differences were observed in shape and site of umbilical cord insertion. Conclusion: The gross morphology of placentae with gestational diabetes mellitus significantly differs from normal pregnancies which may be associated with alteration in physiological functioning of placenta and ultimately fetal outcome.

  9. Arf and RhoA regulate both the cytosolic and the membrane-bound phospholipase D from human placenta

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Hansen, Harald S.; Provost, J.J.;

    1997-01-01

    proteins 1 µM mArf3 (2-fold) and 0.37 nM RhoA (2-fold). This is the first report to show RhoA activation of a cytosolic PLD. The activation by mArf3 was maintained after partial purification on DEAE Sepharose of the enzyme. We have previously reported the existence of a membrane-bound PLD from human...... for the inhibitory effect. Furthermore, placental membrane PLD was activated by 30 µM GTP¿S (4-fold) and by mArf3 (1 µM) and RhoA (0.37 nM) by a factor of 3 and 2, respectively. The solubilized membrane phospholipase D was partially purified to a basal specific activity of 25-37 nmol/min/mg. This preparation...

  10. Mesenchymal stromal cells from the human placenta promote neovascularization in a mouse model in vivo.

    Science.gov (United States)

    Kinzer, M; Hingerl, K; König, J; Reinisch, A; Strunk, D; Huppertz, B; Lang, I

    2014-07-01

    Cell transplantation is a promising strategy in regenerative medicine for revascularization of ischemic tissues. Based on our observation that placental mesenchymal stromal cells (PMSC) enhance endothelial cell viability in vitro via secretion of angiogenic factors, we asked whether PMSC support vascular growth in vivo. PMSC were isolated from amnion and placental endothelial cells (PLEC) from chorion and either separately or co-transplanted subcutaneously into immune-deficient mice. Co-transplantation resulted in a higher number of perfused human vessels (CD31+/vimentin+) containing mouse glycophorin A+ erythrocytes. Results indicate positive effects of PMSC on neovascularization in vivo, making them attractive candidates to create autologous PMSC/PLEC pairs for research and transplantation.

  11. Human Umbilical Cord Mesenchymal Stem Cells Therapy in Cyclophosphamide-Induced Premature Ovarian Failure Rat Model

    Directory of Open Access Journals (Sweden)

    Dan Song

    2016-01-01

    Full Text Available Premature ovarian failure (POF is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX- induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescence in situ hybridization (FISH. The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.

  12. Placenta Percreta Presenting with Delayed Haematuria.

    Science.gov (United States)

    Wagaskar, Vinayak Gorakhanath; Daga, Sudarshan Omprakash; Patwardhan, Sujata Kiran

    2015-12-01

    Placenta percreta presents as life threatening complications with bladder invasion. A condition of placenta invading urinary bladder presented with differential diagnosis of gestational trophoblastic neoplasia on imaging and responded to chemotherapy. A 35-year-old primi-gravida presented at term with per vaginal bleeding. During caesarian section placental mass totally invading uterine myometrium was found. She was given single dose of Methotrexate. After 2 months she presented with gross haematuria with clot retention two times. Her MRI was suggestive of gestational trophoblastic neoplasia of size 19 X 10 X 13cm. Her beta-Human Chorionic Gonadotropin levels were 691.23 mIU/ml. She was given total four doses of methotrexate. At present size of mass was 1.6 X1.3X 1.1cm. Her beta Human Chorionic Gonadotropin level dropped down to 2mIU/ml. Patient was not willing for further intervention or for follow up.

  13. The in vivo study of myeloprotection by GST-π gene transfected human cord blood hematopoietic stem cells transplantation

    Institute of Scientific and Technical Information of China (English)

    Yang Xingsheng; Yu Chenghao; Kong Yawei; Jiang Jie; Dong Ruiying; Cui Baoxia; Wang Lijie; Jiang Sen

    2003-01-01

    Objective:To investigate the influence of GST-π gene transfer into human cord blood hematopoietic stem cells on their drug resistance against anti-tumor drugs in vivo.Methods:GST-π gene transfection into human cord blood CD34+ cells was carried out using a retrovirus vector PLJ-GST-π with the aid of fibronectin.Successful gene transfer was confirmed by in vitro colony assay and RT-PCR.GST-π gene transduced human cord blood CD34+ cells were then engrafted into 4-week-old total body irradiated NOD/Scid mice and carboplatin was intraperitoneally administered sequentially at 4 weeks interval 4 weeks after engraftment.Results:Peripheral blood(PB) WBC was significantly higher in GST-π mice than control mice after 2 course of carboplatin.Retroviral GST-π expression in bone marrow hematopoietic progenitor cells of recipient mice was detected by RT-PCR 16 weeks after Xenotransplantation.Conclusion:The transfection of GST-π gene could confer,to some extent,resistance to cord blood stem cells against carboplatin in vivo.

  14. Metalloprotease Dependent Release of Placenta Derived Fractalkine

    OpenAIRE

    Monika Siwetz; Astrid Blaschitz; Julia Kremshofer; Jelena Bilic; Gernot Desoye; Berthold Huppertz; Martin Gauster

    2014-01-01

    The chemokine fractalkine is considered as unique since it exists both as membrane-bound adhesion molecule and as shed soluble chemoattractant. Here the hypothesis was tested whether placental fractalkine can be shed and released into the maternal circulation. Immunohistochemical staining of human first trimester and term placenta sections localized fractalkine at the apical microvillous plasma membrane of the syncytiotrophoblast. Gene expression analysis revealed abundant upregulation in pla...

  15. Human placenta-derived adherent cell treatment of experimental stroke promotes functional recovery after stroke in young adult and older rats.

    Directory of Open Access Journals (Sweden)

    Amjad Shehadah

    Full Text Available BACKGROUND: Human Placenta-Derived Adherent Cells (PDAC® are a novel mesenchymal-like cell population derived from normal human placental tissue. PDA-001 is a clinical formulation of PDAC® developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo in young adult (2-3 month old and older rats (10-12 months old. METHODS: To evaluate efficacy and determine the optimal number of transplanted cells, young adult Wistar rats were subjected to MCAo and treated 1 day post MCAo with 1×10(6, 4×10(6 or 8×10(6 PDA-001 cells (i.v., vehicle or cell control. 4×10(6 or 8×10(6 PDA-001 cells were also tested in older rats after MCAo. Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS and foot-fault test. Young adult rats were sacrificed 56 days after MCAo, older rats were sacrificed 29 days after MCAo, and lesion volumes were measured using H&E. Immunohistochemical stainings for bromodeoxyuridine (BrdU and von Willebrand Factor (vWF, and synaptophysin were performed. RESULTS: In young adult rats, treatment with 4×10(6 PDA-001 cells significantly improved functional outcome after stroke (p<0.05. In older rats, significant functional improvement was observed with PDA-001 cell therapy in both of the 4×10(6 and 8×10(6 treatment groups. Functional benefits in young adult and older rats were associated with significant increases in the number of BrdU immunoreactive endothelial cells, vascular density and perimeter in the ischemic brain, as well as significantly increased synaptophysin expression in the ischemic border zone (p<0.05. CONCLUSION: PDA-001 treatment significantly improved functional outcome after stroke in both young adult and older rats. The neurorestorative effects induced by PDA-001 treatment may be related to increased

  16. Elemental analysis of human amniotic fluid and placenta by total-reflection X-ray fluorescence and energy-dispersive X-ray fluorescence: child weight and maternal age dependence

    Science.gov (United States)

    Carvalho, M. L.; Custódio, P. J.; Reus, U.; Prange, A.

    2001-11-01

    This work is an attempt to evaluate the possible influence of the mother's age in trace element concentrations in human amniotic fluid and placenta and whether these concentrations are correlated to the weight of the newborn infants. Total-reflection X-ray fluorescence (TXRF) was used to analyze 16 amniotic fluid samples, and the placenta samples were analyzed by energy dispersive X-ray fluorescence (EDXRF). The whole samples were collected during delivery from healthy mothers and healthy infants and full-term pregnancies. According to the age of the mother, three different groups were considered: 20-25, 25-30 and 30-40 years old. Only two mothers were aged more than 35 years. The weight of the infants ranged from 2.56 to 4.05 kg and three groups were also considered: 2.5-3, 3-3.5 and 3.5-4 kg. The organic matrix of the amniotic fluid samples was removed by treatment with HNO 3 followed by oxygen plasma ashing. Yttrium was used as the internal standard for TXRF analysis. Placenta samples were lyophilized and analyzed by EDXRF without any chemical treatment. Very low levels of Ni and Sr were found in the amniotic fluid samples, and were independent of the age of the mother and weight of the child. Cr, Mn, Se and Pb were at the level of the detection limit. Zn, considered one of the key elements in neonatal health, was not significantly different in the samples analyzed; however, it was weakly related to birth weigh. The concentrations obtained ranged from 0.11 to 0.92 mg/l and 30 to 65 μg/g in amniotic fluid and placenta, respectively. The only two elements which seemed to be significantly correlated with mother's age and newborn weight were Ca and Fe for both types of sample: Ca levels were increased in heavier children and older mothers; however, Fe increased with increasing maternal age, but decreased for heavier babies. The same conclusions were obtained for placenta and amniotic fluid samples. Cu is closely associated with Fe in its function in the organism

  17. Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    WU Zhi-yuan; HUI Guo-zhen; LU Yi; WU Xin; GUO Li-he

    2006-01-01

    Background Human amniotic epithelial cells (HAECs), which have several characteristics similar to stem cells,therefore could possibly be used in cell therapy without creating legal or ethical problems. In this study, we transplanted HEACs into the injured spinal cord of rats to investigate if the cells can improve the rats' hindlimb motor function.Methods HAECs were obtained from a piece of fresh amnion, labeled with Hoechst33342, and transplanted into the site of complete midthoracic spinal transections in adult rats. The rats (n=21) were randomly divided into three groups: Sham-operation group (n=7), cells-graft group (n=7), and PBS group (n=7). One rat of each group was killed for histological analysis at the second week after the transplantation. The other six rats of each group were killed for histological analysis after an 8-week behavioral testing. Hindlimb motor function was assessed by using the open-field BBB scoring system. Survival rate of the graft cells was observed at second and eighth weeks after the transplantation. We also detected the myelin sheath fibers around the lesions and the size of the axotomized red nucleus. A one-way ANOVA was used to compare the means among the groups. The significance level was set at P<0.05.Results The graft HAECs survived for a long time (8 weeks) and integrated into the host spinal cord without immune rejection. Compared with the control group, HAECs can promote the regeneration and sprouting of the axons, improve the hindlimb motor function of the rats (BBB score: cells-graft group 9.0± 0.89 vs PBS group 3.7± 1.03, P<0.01), and inhibit the atrophy of axotomized red nucleus [cells-graft group (526.47 ± 148.42) μm2 vs PBS group (473.69±164.73) μm2, P<0.01].Conclusion Transplantation of HAECs can improve the hindlimb motor function of rats with spinal cord injury.

  18. Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

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    Di Gioacchino, Mario [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Medicine and Science of Ageing University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy)], E-mail: m.digioacchino@unich.it; Petrarca, Claudia; Perrone, Angela [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Medicine and Science of Ageing University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Farina, Massimo; Sabbioni, Enrico; Hartung, Thomas [Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Martino, Simone [Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Esposito, Diana L. [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Lotti, Lavinia Vittoria [Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Mariani-Costantini, Renato [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy)

    2008-03-15

    Stem cells are a key target of environmental toxicants, but little is known about their toxicological responses. We aimed at developing an in-vitro model based on adult human stem cells to identify biomarkers of heavy metal exposure. To this end we investigated the responses of human CD34+ hematopoietic progenitor cells to hexavalent chromium (Cr[VI]) and cadmium (Cd). Parallel cultures of CD34+ cells isolated from umbilical cord blood were exposed for 48 h to 0.1 {mu}M and 10 {mu}M Cr(VI) or Cd. Cultures treated with 10 {mu}M Cr(VI) or Cd showed marked cell loss. Ultrastructural analysis of surviving cells revealed prominent autophagosomes/autophagolysosomes, which is diagnostic of autophagy, associated with mitochondrial damage and replication, dilatation of the rough endoplasmic reticulum and Golgi complex, cytoplasmic lipid droplets and chromatin condensation. Treated cells did not show the morphologic hallmarks of apoptosis. Treatment with 0.1 {mu}M Cr(VI) or Cd did not result in cell loss, but at the ultrastructural level cells showed dilated endoplasmic reticulum and evidence of mitochondrial damage. We conclude that autophagy is implicated in the response of human hematopoietic stem cells to toxic concentrations of Cr(VI) and Cd. Autophagy, which mediates cell survival and death under stress, deserves further evaluation to be established as biomarker of metal exposure.

  19. Optimal time for human umbilical cord blood cell transplantation in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    XING Yun-li; SHEN Lu-hua; LI Hong-wei; ZHANG Yu-chen; ZHAO Lin; ZHAO Shu-mei; XU Qing

    2009-01-01

    Background Cell therapy for cardiac regeneration is still under investigation. To date there have been a limited number of studies describing the optimal time for cell injection. The present study aimed to examine the optimal time for human umbilical cord blood cells (HUCBCs) transplantation after myocardial infarction (MI).Methods The animals underwent MI by ligation of the left anterior descending coronary artery and received an intravenous injection of equal volumes of HUCBCs or phosphate buffered saline at days 1,5,10 and 30 after MI. HUCBCs were detected by immunostaining against human human leucocyte antigen (HLA). Cardiac function, histological analysis and measurement of vascular endothelial growth factor (VEGF) were performed 4 weeks after cell transplantation. Results HUCBCs transplantation could improve cardiac function in rats that received transplantation at 5 and 10 days after MI. The best benefit was achieved in rats that received cells at 10-day after MI. Survival of engrafted HUCBCs, angiogenesis and VEGF expression were more obvious in the 10-day transplantation group than in the other transplantation groups. No evidence of cardiomyocyte regeneration was detected in any transplanted rats. Conclusions HUCBCs transplantation could improve cardiac function in rats that received HUCBCs at days 5 and 10 after MI with the optimal time for transplantation being 10 days post MI. Angiogenesis, but not cardiomyocyte regeneration, played a key role in the cardiac function improvement.

  20. Induction of pluripotency in human umbilical cord mesenchymal stem cells in feeder layer-free condition.

    Science.gov (United States)

    Daneshvar, Nasibeh; Rasedee, Abdullah; Shamsabadi, Fatemeh Tash; Moeini, Hassan; Mehrboud, Parvaneh; Rahman, Heshu Sulaiman; Boroojerdi, Mohadeseh Hashem; Vellasamy, Shalini

    2015-12-01

    Induced Pluripotent Stem Cells (iPSCs) has been produced by the reprogramming of several types of somatic cells through the expression of different sets of transcription factors. This study consists of a technique to obtain iPSCs from human umbilical cord mesenchymal stem cells (UC-MSCs) in a feeder layer-free process using a mini-circle vector containing defined reprogramming genes, Lin28, Nanog, Oct4 and Sox2. The human MSCs transfected with the minicircle vector were cultured in iPSCs medium. Human embryonic stem cell (ESC)-like colonies with tightly packed domelike structures appeared 7-10 days after the second transfection. In the earliest stages, the colonies were green fluorescence protein (GFP)-positive, while upon continuous culture and passage, genuine hiPSC clones expressing GFP were observed. The induced cells, based on the ectopic expression of the pluripotent markers, exhibited characteristics similar to the embryonic stem cells. These iPSCs demonstrated in vitro capabilities for differentiation into the three main embryonic germ layers by embryoid bodies formation. There was no evidence of transgenes integration into the genome of the iPSCs in this study. In conclusion, this method offers a means of producing iPSCs without viral delivery that could possibly overcome ethical concerns and immune rejection in the use of stem cells in medical applications.

  1. Isolation and Characterisation of Mesenchymal Stem Cells from Different Regions of the Human Umbilical Cord

    Directory of Open Access Journals (Sweden)

    Claire Mennan

    2013-01-01

    Full Text Available Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs sourced from several different cord regions, including artery, vein, cord lining, and Wharton’s jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics.

  2. Isolation and Characterisation of Mesenchymal Stem Cells from Different Regions of the Human Umbilical Cord

    Science.gov (United States)

    Wright, Karina; Bhattacharjee, Atanu; Balain, Birender; Richardson, James; Roberts, Sally

    2013-01-01

    Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs) sourced from several different cord regions, including artery, vein, cord lining, and Wharton's jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics. PMID:23984420

  3. Pressor response to passive walking-like exercise in spinal cord-injured humans.

    Science.gov (United States)

    Ogata, Hisayoshi; Higuchi, Yukiharu; Ogata, Toru; Hoshikawa, Shinya; Akai, Masami; Nakazawa, Kimitaka

    2009-04-01

    To examine blood pressure responses during passive walking-like exercise in the standing posture (PWE) in spinal cord-injured (SCI) humans. Twelve motor-complete SCI individuals (cervical level 6 to thoracic level 12, ASIA grade: A or B) and twelve able-bodied controls (CON) participated in this study. SCI individuals were divided into a group with injury level at or above thoracic (T) 6 (HSCI, n = 7) and a group with injury level at or below T10 (LSCI, n = 5). Subjects carried out 6-minute quiet standing and then 12-minute PWE at 1 Hz using a gait training apparatus that enables subjects to stand and move their legs passively. Mean arterial blood pressures (MAPs) at standing in HSCI, LSCI and CON were 69 +/- 5, 83 +/- 4 and 93 +/- 2 mmHg, respectively. MAP changed significantly during PWE only in HSCI and CON, increasing to 88 +/- 4 (P < 0.001) and 98 +/- 1 mmHg (P < 0.01), respectively. The former group showed a larger increase in MAP (P < 0.001). Spinal sympathetic reflexes can be induced in a region isolated from the brainstem in response to a stimulus originating below the level of the spinal cord injury, and the magnitude of increase in blood pressure is greater in SCI individuals with lesion level at or above T6 due to loss of supraspinal control of the major sympathetic outflow. This central mechanism may be one of the reasons why greater pressor response to PWE was observed in HSCI.

  4. Human Umbilical Cord Blood Cells or Estrogen may be Beneficial in Treating Heatstroke

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    Sheng-Hsien Chen

    2007-03-01

    Full Text Available This current review summarized animal models of heatstroke experimentation that promote our current knowledge of therapeutic effects on cerebrovascular dysfunction, coagulopathy, and/or systemic inflammation with human umbilical cord blood cells (HUCBCs or estrogen in the setting of heatstroke. Accumulating evidences have demonstrated that HUCBCs provide a promising new therapeutic method against neurodegenerative diseases, such as stroke, traumatic brain injury, and spinal cord injury as well as blood disease. More recently, we have also demonstrated that postor pretreatment by HUCBCs may resuscitate heatstroke rats with by reducing circulatory shock, and cerebral nitric oxide overload and ischemic injury. Moreover, CD34+ cells sorted from HUCBCs may improve survival by attenuating inflammatory, coagulopathy, and multiorgan dysfunction during experimental heatstroke. Many researchers indicated pro(e.g. tumor necrosis factor-α [TNF-α] and anti-inflammatory (e.g. interleukin-10 [IL-10] cytokines in the peripheral blood stream correlate with severity of circulatory shock, cerebral ischemia and hypoxia, and neuronal damage occurring in heatstroke. It has been shown that intravenous administration of CD34+ cells can secrete therapeutic molecules, such as neurotrophic factors, and attenuate systemic inflammatory reactions by decreasing serum TNF-α but increasing IL-10 during heatstroke. Another line of evidence has suggested that estrogen influences the severity of injury associated with cerebrovascular shock. Recently, we also successfully demonstrated estrogen resuscitated heatstroke rats by ameliorating systemic inflammation. Conclusively, HUCBCs or estrogen may be employed as a beneficial therapeutic strategy in prevention and repair of cerebrovascular dysfunction, coagulopathy, and/or systemic inflammation during heatstroke.

  5. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans.

    Directory of Open Access Journals (Sweden)

    Enrico Rejc

    Full Text Available Sensory and motor complete spinal cord injury (SCI has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs' muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25-60 Hz resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical.

  6. The Effects of Thermal Preconditioning on Oncogenic and Intraspinal Cord Growth Features of Human Glioma Cells.

    Science.gov (United States)

    Zeng, Xiang; Han, Inbo; Abd-El-Barr, Muhammad; Aljuboori, Zaid; Anderson, Jamie E; Chi, John H; Zafonte, Ross D; Teng, Yang D

    2016-12-13

    The adult rodent spinal cord presents an inhibitory environment for donor cell survival, impeding efficiency for xenograft-based modeling of gliomas. We postulated that mild thermal preconditioning may influence the fate of the implanted tumor cells. To test this hypothesis, high-grade human astrocytoma G55 and U87 cells were cultured under 37C and 38.5C to mimic regular experimental or core body temperatures of rodents, respectively. In vitro, the 38.5C-conditioned cells, relative to 37C, grew slightly faster. Compared to U87 cells, G55 cells demonstrated a greater response to the temperature difference. Hyperthermal culture markedly increased production of Hsp27 in most G55 cells, but only promoted transient expression of cancer stem cell marker CD133 in a small cell subpopulation. We subsequently transplanted G55 cells following 37C or 38.5C culture into the C2 or T10 spinal cord of adult female immunodeficient rats (3 rats/each locus/per temperature; total: 12 rats). Systematic analyses revealed that 38.5C-preconditioned G55 cells grew more malignantly at either C2 or T10 as determined by tumor size, outgrowth profile, resistance to bolus intratumor administration of 5-fluorouracil (0.1 mol), and posttumor survival (p0.05; n=6/group). Therefore, thermal preconditioning of glioma cells may be an effective way to influence the in vitro and in vivo oncological contour of glioma cells. Future studies are needed for assessing the potential oncogenic modifying effect of hyperthermia regimens on glioma cells.

  7. The Human Umbilical Cord: A Novel Substitute for Reconstruction of the Extrahepatic Bile Duct

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    Jiong Lu

    2012-01-01

    Full Text Available Reconstruction of the extrahepatic bile duct following bile duct injury or defect is one of the most common challenges for hepatobiliary surgeons. There are currently a number of surgical strategies such as biliary-enteric anastomosis, end-to-end anastomosis and autologous tissue substitute. However, sphincter of Oddi dysfunction as well as biliary stricture may occur after surgical anastomosis. Also, insufficient tissue quantity remains a problem associated with the application of tissue substitute. Therefore, considerable attention has been attracted to explore a new replacement material of the bile duct for biliary reconstruction. The human umbilical cord (HUC is abundant in resource and is convenient to collect, including two arteries and one vein, whose diameters are close to that of the common bile duct. In order to reduce immunogenicity (foreign-body reaction, cells and major histocompatibility complex (MHC antigens can be removed from the HUC and the remaining tissue (extracellular matrix, ECM can be used as a scaffold. The HUC provides a rich source of mesenchymal stem cells (MSCs. A current study has demonstrated that MSCs are able to differentiate into biliary epithelial cells in vivo and in vitro with low immunogenicity, which can be used as seed cells. The HUC might be a promising composite material of a scaffold (ECM and seed cells (biliary epithelial cells, for bile duct replacement in situ without removal of sphincter of Oddi, or biliary stricture. In addition, the patients’ own umbilical cord without any foreign-body reaction can be directly banked for possible future use in bile duct reconstruction. Therefore, we hypothesise that the HUC may be a novel substitute for reconstruction of the extrahepatic bile duct.

  8. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans.

    Science.gov (United States)

    Rejc, Enrico; Angeli, Claudia; Harkema, Susan

    2015-01-01

    Sensory and motor complete spinal cord injury (SCI) has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs' muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25-60 Hz) resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical.

  9. Osteogenic potential of human umbilical cord-derived mesenchymal stromal cells cultured with umbilical cord blood-derived fibrin: a preliminary study.

    Science.gov (United States)

    Baba, Kyoko; Yamazaki, Yasuharu; Ishiguro, Masashi; Kumazawa, Kenichi; Aoyagi, Kazuya; Ikemoto, Shigehiro; Takeda, Akira; Uchinuma, Eiju

    2013-12-01

    This study examined the potential for osteogenesis via regenerative medicine using autologous tissues (umbilical cord (UC) and umbilical cord blood (UCB)) in nude mice. The study was designed to provide the three elements required for regenerative medicine (cell, scaffold, and growth factor) and autoserum for culture by means of autologous tissues. Mesenchymal stromal cells were obtained from UC (UC-MSCs). Fibrin, platelet-rich-plasma, and autoserum were obtained from UCB as scaffold, growth factor and serum for culture respectively. UC-MSCs were obtained from Wharton jelly and cultured with UCB-derived fibrin (UCB-fibrin) for 3-4 weeks to induce their differentiation into osteoblasts. They were implanted subcutaneously into the dorsum of male nude mice for 6 weeks prior to undergoing assessment. The assessments performed were haematoxylin and eosin, and alizarin red staining, immunohistochemical staining of human mitochondria, scanning electron microscopy, scanning electron microscopy with energy dispersive X-ray spectrometry and real-time reverse transcriptase-polymerase chain reaction to assess the expressions of osteoblast markers. Consequently, the differentiation of UC-MSCs into osteoblasts and the production of hydroxyapatite were verified. This study suggested the possible formation of bone tissue using biomedical materials obtained from UC and UCB.

  10. Human umbilical cord Wharton's jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration

    Institute of Scientific and Technical Information of China (English)

    Hong Chen; Yan Zhang; Zhijun Yang; Hongtian Zhang

    2013-01-01

    Human umbilical mesenchymal stem cells from Wharton's jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.

  11. A new method to isolate mesenchymal stem cells from human placenta%胎盘源间充质干细胞分离提取的新方法

    Institute of Scientific and Technical Information of China (English)

    刘洋; 靳继德; 李艳琪; 王洪一; 吴晓冰; 荆永光; 徐潇; 姚尧; 张宇; 吴祖泽

    2015-01-01

    背景:胎盘是获取间充质干细胞的理想来源,在干细胞治疗和再生医学中具有潜在广泛的用途,建立高效分离提取方法有助于其存储和临床应用。目的:分析组织绞碎加酶液消化法培养人胎盘间充质干细胞的生物学特性。方法:采用组织绞碎加酶液消化法分离、富集胎盘组织中间充质干细胞,应用流式细胞术检测细胞表面标记, MTT法分析增殖能力,并采用诱导剂定向诱导胎盘间充质干细胞成脂、成骨和成软骨分化。结果与结论:胎盘组织来源间充质干细胞在体外可稳定长期传代培养,应用流式细胞仪检测结果显示 CD73、CD90、CD105表达阳性,CD11b、CD19、CD34、CD45、HLA-DR表达阴性。胎盘间充质干细胞增殖活跃,第3-5天进入对数生长期,第6天进入平台期。经诱导后,胎盘间充质干细胞具有向脂肪细胞、骨细胞、软骨细胞分化的潜能。结果表明联合利用组织绞碎和酶液消化法可高效获取胎盘间充质干细胞,在体外培养过程中生长稳定,增殖能力强,可长期传代。%BACKGROUND:Placenta is a valuable source of mesenchymal stem cels for stem cel therapy and future application in the field of regenerative medicine. However, conventional methods cannot acquire a large amount of purified human placenta-derived mesenchymal stem cels. Here, we present a new method for isolating human placenta-derived mesenchymal stem cels suitable for banking strategies and for future clinical applications. OBJECTIVE:To analyze the biological characteristics of human placenta-derived mesenchymal stem cels cultured by tissue dissociating and colagenase digestion. METHODS: Human placenta-derived mesenchymal stem cels were obtained from human placenta by tissue dissociating and colagenase digestion method. Immunophenotype was analyzed by flow cytometry. Growth curve was determined by MTT assay, and differentiation ability was

  12. Human embryonic stem cell-derived oligodendrocyte progenitors aid in functional recovery of sensory pathways following contusive spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Angelo H All

    Full Text Available BACKGROUND: Transplantations of human stem cell derivatives have been widely investigated in rodent models for the potential restoration of function of neural pathways after spinal cord injury (SCI. Studies have already demonstrated cells survival following transplantation in SCI. We sought to evaluate survival and potential therapeutic effects of transplanted human embryonic stem (hES cell-derived oligodendrocyte progenitor cells (OPCs in a contusive injury in rats. Bioluminescence imaging was utilized to verify survivability of cells up to 4 weeks, and somatosensory evoked potential (SSEPs were recorded at the cortex to monitor function of sensory pathways throughout the 6-week recovery period. PRINCIPAL FINDINGS: hES cells were transduced with the firefly luciferase gene and differentiated into OPCs. OPCs were transplanted into the lesion epicenter of rat spinal cords 2 hours after inducing a moderate contusive SCI. The hES-treatment group showed improved SSEPs, including increased amplitude and decreased latencies, compared to the control group. The bioluminescence of transplanted OPCs decreased by 97% in the injured spinal cord compared to only 80% when injected into an uninjured spinal cord. Bioluminescence increased in both experimental groups such that by week 3, no statistical difference was detected, signifying that the cells survived and proliferated independent of injury. Post-mortem histology of the spinal cords showed integration of human cells expressing mature oligodendrocyte markers and myelin basic protein without the expression of markers for astrocytes (GFAP or pluripotent cells (OCT4. CONCLUSIONS: hES-derived OPCs transplanted 2 hours after contusive SCI survive and differentiate into OLs that produce MBP. Treated rats demonstrated functional improvements in SSEP amplitudes and latencies compared to controls as early as 1 week post-injury. Finally, the hostile injury microenvironment at 2 hours post-injury initially caused

  13. Cell differentiation mediated by co-culture of human umbilical cord blood stem cells with murine hepatic cells.

    Science.gov (United States)

    Stecklum, Maria; Wulf-Goldenberg, Annika; Purfürst, Bettina; Siegert, Antje; Keil, Marlen; Eckert, Klaus; Fichtner, Iduna

    2015-02-01

    In the present study, purified human cord blood stem cells were co-cultivated with murine hepatic alpha mouse liver 12 (AML12) cells to compare the effect on endodermal stem cell differentiation by either direct cell-cell interaction or by soluble factors in conditioned hepatic cell medium. With that approach, we want to mimic in vitro the situation of preclinical transplantation experiments using human cells in mice. Cord blood stem cells, cultivated with hepatic conditioned medium, showed a low endodermal differentiation but an increased connexin 32 (Cx32) and Cx43, and cytokeratin 8 (CK8) and CK19 expression was monitored by reverse transcription polymerase chain reaction (RT-PCR). Microarray profiling indicated that in cultivated cord blood cells, 604 genes were upregulated 2-fold, with the highest expression for epithelial CK19 and epithelial cadherin (E-cadherin). On ultrastructural level, there were no major changes in the cellular morphology, except a higher presence of phago(ly)some-like structures observed. Direct co-culture of AML12 cells with cord blood cells led to less incisive differentiation with increased sex-determining region Y-box 17 (SOX17), Cx32 and Cx43, as well as epithelial CK8 and CK19 expressions. On ultrastructural level, tight cell contacts along the plasma membranes were revealed. FACS analysis in co-cultivated cells quantified dye exchange on low level, as also proved by time relapse video-imaging of labelled cells. Modulators of gap junction formation influenced dye transfer between the co-cultured cells, whereby retinoic acid increased and 3-heptanol reduced the dye transfer. The study indicated that the cell-co-cultured model of human umbilical cord blood cells and murine AML12 cells may be a suitable approach to study some aspects of endodermal/hepatic cell differentiation induction.

  14. Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

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    Kayaalti, Zeliha, E-mail: kayaalti@ankara.edu.tr [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Kaya-Akyüzlü, Dilek [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Söylemez, Esma [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat (Turkey); Söylemezoğlu, Tülin [Ankara University, Institute of Forensic Sciences, Ankara (Turkey)

    2015-07-15

    Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother–placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR–RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods. - Highlights: • Mothers with H63D gene variants have higher lead levels of their newborn's umbilical cord blood. • Unborn child of women with HD+DD genotypes may be at increased risk of internal exposure to lead. • Maternal HFE status may have an effect on increased placenta, maternal and cord blood lead levels.

  15. Morphological observation of nanobacteria in calcified placenta and umbilical cord blood%钙化胎盘及脐带血中纳米细菌的形态学观察

    Institute of Scientific and Technical Information of China (English)

    刘胜男; 张德纯; 张名均; 郭亚楠; 杨晓容; 杨顺杰

    2013-01-01

    目的 研究纳米细菌(nanobacteria,NB)的分布,寻求检测胎盘钙化NB感染的更好组织来源.方法 收集孕妇胎盘钙化组织和脐带血20例,并以20例正常胎盘组织作对照,分离培养NB;用革兰染色和茜素红染色法、扫描电镜和透射电镜进行形态学鉴定.结果 培养沉淀物符合NB的特性.脐带血NB分离率为80%(16/20),钙化胎盘组织为65%(13/20),均明显高于正常胎盘组织的10%(2/20),X2分别为12.07、9.09,P均<0.01;脐带血与钙化胎盘组织比较,差异无统计学意义(x2=1.33,P>0.05).油镜下脐带血和钙化胎盘组织分离的NB为球状或球杆状,形态相似;茜素红染色脐带血中NB较多且聚集成簇;透射电镜和扫描电镜下NB呈球形,大小为80 ~ 500 nm,并可见毛刺结构.结论 胎盘钙化与NB感染有关,脐带血适用于检测钙化胎盘的NB感染.%Objective To study the distribution of nanobacteria (NB) and explore an appropriate tissue as the source for detection of placental calcification infected with nanobacteria. Methods The calcified placental tissues and umbilical cord blood from 20 pregnant women for isolation and culture of NB, and normal placental tissues were used as controls. The morphological identification of NB was performed with Gram and alizarin red staining and scanning electron microscope (SEM) , transmission electron microscope (TEM). Results The precipitates were corresponding to the characteristics of NB. The isolation rate of NB was 65% (13/20) in the specimens of calcified placental tissues and 80% (16/20) in the cord blood, and both of them were higher than that in normal placental tissues (10% ) with a significantly statistical difference ( chi-square values were 12. 07 and 9. 09 respectively, P 0. 05). The shape of NB isolated from calcified placental tissue and umbilical cord blood under oil lens was spherical or rhabdoid with burr edge, and was globoid with size of 80-500 nm and staining of Gram

  16. Metalloprotease Dependent Release of Placenta Derived Fractalkine

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    Monika Siwetz

    2014-01-01

    Full Text Available The chemokine fractalkine is considered as unique since it exists both as membrane-bound adhesion molecule and as shed soluble chemoattractant. Here the hypothesis was tested whether placental fractalkine can be shed and released into the maternal circulation. Immunohistochemical staining of human first trimester and term placenta sections localized fractalkine at the apical microvillous plasma membrane of the syncytiotrophoblast. Gene expression analysis revealed abundant upregulation in placental fractalkine at term, compared to first trimester. Fractalkine expression and release were detected in the trophoblast cell line BeWo, in primary term trophoblasts and placental explants. Incubation of BeWo cells and placental explants with metalloprotease inhibitor Batimastat inhibited the release of soluble fractalkine and at the same time increased the membrane-bound form. These results demonstrate that human placenta is a source for fractalkine, which is expressed in the syncytiotrophoblast and can be released into the maternal circulation by constitutive metalloprotease dependent shedding. Increased expression and release of placental fractalkine may contribute to low grade systemic inflammatory responses in third trimester of normal pregnancy. Aberrant placental metalloprotease activity may not only affect the release of placenta derived fractalkine but may at the same time affect the abundance of the membrane-bound form of the chemokine.

  17. Human umbilical cord mesenchymal stem cells promote peripheral nerve repairvia paracrine mechanisms

    Institute of Scientific and Technical Information of China (English)

    Zhi-yuan Guo; Xun Sun; Xiao-long Xu; Qing Zhao; Jiang Peng; Yu Wang

    2015-01-01

    Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the para-crine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These ifndings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

  18. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

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    Yuanyuan Zhao

    2015-01-01

    Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

  19. Reflex responses to combined hip and knee motion in human chronic spinal cord injury

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    Ming Wu, PhD

    2010-04-01

    Full Text Available The relative contributions of hip and knee proprioceptors to the origination of extensor spasms were examined in 11 subjects with chronic spinal cord injury (SCI. Ramp and hold extension and combined hip and knee oscillation movements were imposed to the right leg while the ankle was held in a static position by a custom-designed robot. Isometric joint torques of the hip, knee, and ankle and surface electromyograms (EMGs from seven leg muscles were recorded following controlled hip and knee extension. A stereotypical torque response consisting of hip flexion, knee extension, and ankle plantar flexion was observed following hip and knee perturbations. Further, the hip or knee joint posture modulated the spastic reflexes triggered by the extension movement of the other joint, with larger responses observed with the hip and knee extended. In addition, combined hip and knee oscillation movements were imposed to one leg with four different phasing conditions. The phasing between the hip and knee modulated the reflex activity triggered by hip and knee oscillations. The EMG patterns of the spastic reflexes were generally consistent with muscle timing during locomotion in human SCI. This knowledge may help identify rehabilitation strategies that produce functional movements in human SCI.

  20. Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

    Directory of Open Access Journals (Sweden)

    Zhi-yuan Guo

    2015-01-01

    Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

  1. Twitch and tetanic properties of human thenar motor units paralyzed by chronic spinal cord injury.

    Science.gov (United States)

    Häger-Ross, C K; Klein, C S; Thomas, C K

    2006-07-01

    Little is known about how human motor units respond to chronic paralysis. Our aim was to record surface electromyographic (EMG) signals, twitch forces, and tetanic forces from paralyzed motor units in the thenar muscles of individuals (n = 12) with chronic (1.5-19 yr) cervical spinal cord injury (SCI). Each motor unit was activated by intraneural stimulation of its motor axon using single pulses and trains of pulses at frequencies between 5 and 100 Hz. Paralyzed motor units (n = 48) had small EMGs and weak tetanic forces (n = 32 units) but strong twitch forces, resulting in half-maximal force being achieved at a median of only 8 Hz. The distributions for cumulative twitch and tetanic forces also separated less for paralyzed units than for control units, indicating that increases in stimulation frequency made a smaller relative contribution to the total force output in paralyzed muscles. Paralysis also induced slowing of conduction velocities, twitch contraction times and EMG durations. However, the elevated ratios between the twitch and the tetanic forces, but not contractile speed, correlated significantly with the extent to which unit force summated in response to different frequencies of stimulation. Despite changes in the absolute values of many electrical and mechanical properties of paralyzed motor units, most of the distributions shifted uniformly relative to those of thenar units obtained from control subjects. Thus human thenar muscles paralyzed by SCI retain a population of motor units with heterogeneous contractile properties because chronic paralysis influenced all of the motor units similarly.

  2. Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes

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    Xingfu Li

    2016-01-01

    Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2 and decreased type I collagen (COL1 protein expression levels. SRY-box 9 (SOX9 mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

  3. Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model.

    Science.gov (United States)

    Drobyshevsky, Alexander; Cotten, C Michael; Shi, Zhongjie; Luo, Kehuan; Jiang, Rugang; Derrick, Matthew; Tracy, Elizabeth T; Gentry, Tracy; Goldberg, Ronald N; Kurtzberg, Joanne; Tan, Sidhartha

    2015-01-01

    Cerebral palsy (CP) has a significant impact on both patients and society, but therapy is limited. Human umbilical cord blood cells (HUCBC), containing various stem and progenitor cells, have been used to treat various brain genetic conditions. In small animal experiments, HUCBC have improved outcomes after hypoxic-ischemic (HI) injury. Clinical trials using HUCBC are underway, testing feasibility, safety and efficacy for neonatal injury as well as CP. We tested HUCBC therapy in a validated rabbit model of CP after acute changes secondary to HI injury had subsided. Following uterine ischemia at 70% gestation, we infused HUCBC into newborn rabbit kits with either mild or severe neurobehavioral changes. Infusion of high-dose HUCBC (5 × 10(6) cells) dramatically altered the natural history of the injury, alleviating the abnormal phenotype including posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed lesser but still significant improvement. The swimming test, however, showed that joint function did not restore to naïve control function in either group. Tracing HUCBC with either MRI biomarkers or PCR for human DNA found little penetration of HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial effects were not due to cellular integration or direct proliferative effects but rather to paracrine signaling. This is the first study to show that HUCBC improve motor performance in a dose-dependent manner, perhaps by improving compensatory repair processes. © 2015 S. Karger AG, Basel.

  4. Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells

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    Hass Ralf

    2010-07-01

    Full Text Available Abstract Following cultivation of distinct mesenchymal stem cell (MSC populations derived from human umbilical cord under hypoxic conditions (between 1.5% to 5% oxygen (O2 revealed a 2- to 3-fold reduced oxygen consumption rate as compared to the same cultures at normoxic oxygen levels (21% O2. A simultaneous measurement of dissolved oxygen within the culture media from 4 different MSC donors ranged from 15 μmol/L at 1.5% O2 to 196 μmol/L at normoxic 21% O2. The proliferative capacity of the different hypoxic MSC populations was elevated as compared to the normoxic culture. This effect was paralleled by a significantly reduced cell damage or cell death under hypoxic conditions as evaluated by the cellular release of LDH whereby the measurement of caspase3/7 activity revealed little if any differences in apoptotic cell death between the various cultures. The MSC culture under hypoxic conditions was associated with the induction of hypoxia-inducing factor-alpha (HIF-1α and an elevated expression of energy metabolism-associated genes including GLUT-1, LDH and PDK1. Concomitantly, a significantly enhanced glucose consumption and a corresponding lactate production could be observed in the hypoxic MSC cultures suggesting an altered metabolism of these human stem cells within the hypoxic environment.

  5. Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo.

    Directory of Open Access Journals (Sweden)

    Santiago Roura

    Full Text Available Stem cell therapies are promising strategies to regenerate human injured tissues, including ischemic myocardium. Here, we examined the acquisition of properties associated with vascular growth by human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs, and whether they promoted vascular growth in vivo. UCBMSCs were induced in endothelial cell-specific growth medium (EGM-2 acquiring new cell markers, increased Ac-LDL uptake, and migratory capacity as assessed by qRT-PCR, Western blotting, indirect immunofluorescence, and invasion assays. Angiogenic and vasculogenic potentials could be anticipated by in vitro experiments showing self organization into Matrigel-mediated cell networks, and activation of circulating angiogenic-supportive myeloid cells. In mice, following subcutaneous co-injection with Matrigel, UCBMSCs modified to co-express bioluminescent (luciferases and fluorescent proteins were demonstrated to participate in the formation of new microvasculature connected with the host circulatory system. Response of UCBMSCs to ischemia was explored in a mouse model of acute myocardial infarction (MI. UCBMSCs transplanted using a fibrin patch survived 4 weeks post-implantation and organized into CD31(+network structures above the infarcted myocardium. MI-treated animals showed a reduced infarct scar and a larger vessel-occupied area in comparison with MI-control animals. Taken together, the presented results show that UCBMSCs can be induced in vitro to acquire angiogenic and vasculogenic properties and contribute to vascular growth in vivo.

  6. Placenta accreta and anesthesia: A multidisciplinary approach

    Directory of Open Access Journals (Sweden)

    R S Khokhar

    2016-01-01

    Full Text Available Placenta accreta (an abnormally adherent placenta is one of the two leading causes of peripartum hemorrhage and the most common indication for peripartum hysterectomy. Placenta accreta may be associated with significant maternal hemorrhage at delivery owing to the incomplete placental separation. When placenta accreta is diagnosed before delivery, a multidisciplinary approach may improve patient outcome.

  7. Placenta accreta and anesthesia: A multidisciplinary approach.

    Science.gov (United States)

    Khokhar, R S; Baaj, J; Khan, M U; Dammas, F A; Rashid, N

    2016-01-01

    Placenta accreta (an abnormally adherent placenta) is one of the two leading causes of peripartum hemorrhage and the most common indication for peripartum hysterectomy. Placenta accreta may be associated with significant maternal hemorrhage at delivery owing to the incomplete placental separation. When placenta accreta is diagnosed before delivery, a multidisciplinary approach may improve patient outcome.

  8. Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    HU Cheng-heng; WU Gui-fu; WANG Xiao-qing; YANG Yan-hua; DU Zhi-min; HE Xiao-hong; XIANG Peng

    2006-01-01

    Background Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI.Methods Forty-five male Wistar rats were randomized into three groups: MI or control group (n=15), MI plus cell transplantation (n=15), and sham group (n=15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations.Results The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart.Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08±8.10) mmHg vs (30.82±9.59) mmHg, P<0.05], increase in +dp/dtmax [(4.29± 1.27)mmHg/ms vs (3.24±0.75) mmHg/ms, P<0.05), and increase in -dp/dtmax [(3.71 ±0.79) mmHg/ms vs (3.00±0.49) mmHg/ms, P<0.05] among MI group with hUCBC transplantation when compared with MI/control group.Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33±2.69)% vs (11.10±3.75)%, P< 0.01]. Based on immunostaining of α-actin, the numbers of microvessels were significantly (P<0.01) increased at the boundary of

  9. Angptl4 maintains in vivo repopulation capacity of CD34+ human cord blood cells.

    Science.gov (United States)

    Blank, Ulrika; Ehrnström, Birgitta; Heinz, Niels; Nilsson, Eva; Brun, Ann; Baum, Christopher; Schiedlmeier, Bernhard; Karlsson, Stefan

    2012-09-01

    Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass an attractive approach that would substantially broaden the clinical applicability of HSCs derived from cord blood (CB). Recently, members of the angiopoietin-like (Angptl) family of growth factors were shown to expand both murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion of human NOD/SCID-repopulating cells (SRCs) ex vivo. Here, we sought to evaluate the potential of additional Angptls to expand human SRCs from CB. Additionally, the purpose of this study was to evaluate the reproducibility of Angptl-mediated expansion of SRCs across independent experiments. Human CD34(+) cells from CB were cultured in vitro for eleven or 8 d in the presence or absence of Angptls. The reconstitution capacity of expanded cells was subsequently measured in vivo by transplantation into NOD/SCID or NSG mice and compared with that of uncultured cells. We report here that Angptl4 functions to maintain SRC activity of CD34(+) CB-derived cells ex vivo as assayed in NOD/SCID and NSG mice. However, all Angptls tested, including Angptl1, Angptl4, and Angptl5, were associated with variation between experiments. Our findings indicate that Angptl4 and Angptl5 can lead to increased engraftment capacity of SRCs, but more frequently, these factors are associated with maintenance of SRC activity during ex vivo culture. Thus, Angptl-mediated expansion of SRCs ex vivo is associated with more interexperimental variation than previously thought. We conclude that Angptls would be useful in instances where there is a need to maintain HSCs ex vivo, such as during transduction for gene therapy applications. © 2012 John Wiley & Sons A/S.

  10. Placenta accreta: the silent invader

    Directory of Open Access Journals (Sweden)

    Seema Dwivedi

    2016-05-01

    Conclusions: Incidence of placenta accrete has increased now a days because of increased incidence of cesarian sections, placenta accreta was seen in primi due to uterine procedures done deliberately in both diagnostic and therapeutic indications. Morbidly adherent placenta is always a nightmare for the obstetrician. Suspicion of a case on history, preoperative confirmation of diagnosis, planned management with bundle of care, with multi-disciplinary approach can save many patients from the clutches of inevitable death. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1501-1505

  11. Human umbilical cord mesenchymal stem cell-loaded amniotic membrane for the repair of radial nerve injury

    Institute of Scientific and Technical Information of China (English)

    Zhi Li; Hanjiao Qin; Zishan Feng; Wei Liu; Ye Zhou; Lifeng Yang; Wei Zhao; Youjun Li

    2013-01-01

    In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cellon the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cellsuspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 × 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after celltransplantation, more than 80%of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improve-ments were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electro-physiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After celltransplantation, no immunological rejec-tions were observed. These findings suggest that human umbilical cord mesenchymal stem cel-loaded amniotic membrane can be used for the repair of radial nerve injury.

  12. Ultrasonographic findings of placenta lacunae and a lack of a clear zone in cases with placenta previa and normal placenta.

    Science.gov (United States)

    Hamada, Shoko; Hasegawa, Junichi; Nakamura, Masamitsu; Matsuoka, Ryu; Ichizuka, Kiyotake; Sekizawa, Akihiko; Okai, Takashi

    2011-11-01

    To evaluate whether the frequencies of placenta lacunae and lack of a clear zone are higher in cases of placenta previa compared with those without it. Ultrasonographic findings just before delivery, including placenta lacunae and lack of a clear zone were prospectively evaluated in consecutive subjects. After collection, a case-control study with 1:5 matched pairs was conducted. The frequencies of ultrasonographic findings were analyzed in cases with placenta previa and normal placenta. Seventy cases with placenta previa and 350 cases with normal placentas were observed. Five and zero cases with abnormal placental adherence were observed in cases with placenta previa and normal placenta, respectively. Lack of a clear zone was observed in 60 and 1.5% of cases with and without the placental adherence (p = 0.001). Placenta lacunae and lack of a clear zone were observed in 31.4 and 9.7% of cases with and without placenta previa [odds ratio (OR) 4.2]. Lack of a clear zone was observed in 5.7 and 0.9% of cases with and without placenta previa (OR 7.0). Placenta lacunae and lack of a clear zone are frequently observed in placenta previa even when there is no adherence of the placenta. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Human Umbilical Cord Blood-Derived Serum for Culturing the Supportive Feeder Cells of Human Pluripotent Stem Cell Lines

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    Ruttachuk Rungsiwiwut

    2016-01-01

    Full Text Available Although human pluripotent stem cells (hPSCs can proliferate robustly on the feeder-free culture system, genetic instability of hPSCs has been reported in such environment. Alternatively, feeder cells enable hPSCs to maintain their pluripotency. The feeder cells are usually grown in a culture medium containing fetal bovine serum (FBS prior to coculture with hPSCs. The use of FBS might limit the clinical application of hPSCs. Recently, human cord blood-derived serum (hUCS showed a positive effect on culture of mesenchymal stem cells. It is interesting to test whether hUCS can be used for culture of feeder cells of hPSCs. This study was aimed to replace FBS with hUCS for culturing the human foreskin fibroblasts (HFFs prior to feeder cell preparation. The results showed that HFFs cultured in hUCS-containing medium (HFF-hUCS displayed fibroblastic features, high proliferation rates, short population doubling times, and normal karyotypes after prolonged culture. Inactivated HFF-hUCS expressed important genes, including Activin A, FGF2, and TGFβ1, which have been implicated in the maintenance of hPSC pluripotency. Moreover, hPSC lines maintained pluripotency, differentiation capacities, and karyotypic stability after being cocultured for extended period with inactivated HFF-hUCS. Therefore, the results demonstrated the benefit of hUCS for hPSCs culture system.

  14. Placenta accreta: adherent placenta due to Asherman syndrome

    DEFF Research Database (Denmark)

    Engelbrechtsen, Line; Langhoff-Roos, Jens; Kjer, Jens Jørgen

    2015-01-01

    It is important to be aware of the risk of abnormally invasive placenta in patients with a history of Asherman syndrome and uterine scarring. A prenatal diagnosis by ultrasonography is useful when planning of mode of delivery.......It is important to be aware of the risk of abnormally invasive placenta in patients with a history of Asherman syndrome and uterine scarring. A prenatal diagnosis by ultrasonography is useful when planning of mode of delivery....

  15. Lean Umbilical Cord - a Case Report.

    Science.gov (United States)

    Rippinger, N; Elsässer, M; Sinn, P; Sohn, C; Fluhr, H

    2016-11-01

    The "lean" umbilical cord (also known as thin-cord syndrome) is a comparatively rare anomaly of the umbilical cord, which has seldom been described in the medical literature. We report on a 35-year-old women who presented to us at 29 + 4 weeks gestation with vaginal bleeding and cervical incompetence subsequently complicated not only by premature rupture of membranes but also acute placental insufficiency requiring emergency caesarean section under general anaesthesia at 31 + 2 weeks gestation. At surgery no obvious cause for the acute placental insufficiency - such as placental abruption, cord prolapse or true knot of the umbilical cord - was found. Other possible causes such as vasa praevia or placenta praevia had previously been excluded sonographically on admission for vaginal bleeding. The only notable intraoperative finding was a macroscopically extremely thin umbilical cord.

  16. Molecular characterization of the Neuronatin gene in the porcine placenta.

    Directory of Open Access Journals (Sweden)

    Ting Gu

    Full Text Available Imprinted genes play important roles in placental and embryonic development. Neuronatin (NNAT, first identified as an imprinted gene in human and mouse brains, played important roles in neuronal differentiation in the brain and in glucose-mediated insulin secretion in pancreatic β cells. In the pig, NNAT was reported to be imprinted in eleven tissues. Our previous microarray hybridization study showed that NNAT was di