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Sample records for cord blood progenitors

  1. Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation.

    Science.gov (United States)

    Mizrahi, K; Stein, J; Pearl-Yafe, M; Kaplan, O; Yaniv, I; Askenasy, N

    2010-07-01

    The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway has selective toxicity to malignant cells. The TRAIL receptors DR4 and DR5 are expressed at low levels in human umbilical cord blood cells (3-15%) and are upregulated by incubation with the cognate ligand, triggering apoptosis in 70-80% of receptor-positive cells (P<0.001). Apoptosis is not induced in hematopoietic progenitors, as determined from sustained severe combined immunodeficiency reconstituting potential and clonogenic activity. Furthermore, elimination of dead cells after incubation with TRAIL for 72 h results in a threefold enrichment in myeloid progenitors. Exposure to TRAIL in semisolid cultures showed synergistic activity of DR4 and granulocyte/macrophage colony-stimulating factor in recruiting lineage-negative (lin(-)) and CD34(+) progenitors and in promoting the formation of large colonies. In murine bone marrow, approximately 30% of lin(-) cells express TRAIL-R2 (the only murine receptor), and the receptor is upregulated after transplantation in cycling and differentiating donor cells that home to the host marrow. However, this receptor is almost ubiquitously expressed in the most primitive (lin(-)SCA-1(+)c-kit(+)) progenitors, and stimulates the clonogenic activity of lin(-) cells (P<0.001), suggesting a tropic function after transplantation. It is concluded that TRAIL does not trigger apoptosis in hematopoietic progenitors, and upregulation of its cognate receptors under stress conditions mediates tropic signaling that supports recovery from hypoplasia.

  2. Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples.

    Directory of Open Access Journals (Sweden)

    Marina Podestà

    Full Text Available Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups.Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15-4.8 vs 0.3% (0.032-2.23 p = 0.0001 and in neonates <32 weeks of gestational age (GA compared to those ≥32 wks GA: 0.95% (range 0.18-4.8 and 0.36% (0.15-3.2 respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL resulted higher compared to term (p = 0.004 and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017. The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168.We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies.

  3. Expansion in bioreactors of human progenitor populations from cord blood and mobilized peripheral blood.

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    Van Zant, G; Rummel, S A; Koller, M R; Larson, D B; Drubachevsky, I; Palsson, M; Emerson, S G

    1994-01-01

    Umbilical cord blood (UCB) and mobilized peripheral blood (MPB) provide an alternate source to bone marrow for transplantation. Expansion in vitro of stem/progenitor cell populations from these sources may provide adult-sized grafts otherwise not attainable because of the limited cell numbers available in the case of UCB or because of numerous rounds of apheresis required for sufficient MPB cells. We asked whether continuous perfusion culture could be employed in ex vivo expansion to produce clinically relevant numbers of stem/progenitor cells from these sources. To evaluate MPB, 1-10 million leukocytes, from patients who had received either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF), were inoculated into bioreactors, with or without irradiated, allogeneic stroma. The growth factor combination in the perfusion medium consisted of interleukin-3 (IL-3), stem cell factor (SCF), GM-CSF and erythropoietin (Epo). Under the best conditions tested, total cell numbers, granulocyte-macrophage colony-forming units (CFU-GM), and long-term culture-initiating cell (LTC-IC) populations were expanded by about 50-, 80-, and 20-fold, respectively, over 14 days. At low cell inocula (1 million), the presence of stroma enhanced the expansion of total cells and CFU-GM but not of LTC-IC. When SCF was not included in the medium, both total cells and CFU-GM expanded to a much lesser extent, but again the expansion of LTC-IC was not affected. At the higher cell inoculum (10 million), expansions of total cells and CFU-GM were equivalent with or without stroma. To evaluate UCB, cells were placed into bioreactors with or without irradiated, allogeneic stroma, and the bioreactors were perfused with medium containing the four standard growth factors. After 6-14 days, in several independent experiments, 20-24 million cells were harvested from bioreactors perfused with SCF-containing medium, irrespective of the

  4. Collagen-Coated Polytetrafluoroethane Membrane Inserts Enhances Chondrogenic Differentiation of Human Cord Blood Multi-Lineage Progenitor Cells

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael

    Background: Articular chondrocytes and bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the favoured cells for cartilage tissue engineering. Umbilical cord blood has proven an alternative source of MSCs and moreover they may be more potent chondroprogenitor cells than bonemarrow...... MSCs. Purpose / Aim of Study: Multilineage progenitor cells (MLPCs) are clonal cord blood-derived MSCs and may therefore provide a cell source with more reproducible outcomes compared to heterogeneous primary MSC cultures. Materials and Methods: We evaluated the chondrogenic potency of MLPCs...

  5. Cord blood-circulating endothelial progenitors for treatment of vascular diseases.

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    Lavergne, M; Vanneaux, V; Delmau, C; Gluckman, E; Rodde-Astier, I; Larghero, J; Uzan, G

    2011-04-01

    Adult peripheral blood (PB) endothelial progenitor cells (EPC) are produced in the bone marrow and are able to integrate vascular structures in sites of neoangiogenesis. EPCs thus represent a potential therapeutic tool for ischaemic diseases. However, use of autologous EPCs in cell therapy is limited by their rarity in adult PB. Cord blood (CB) contains more EPCs than PB, and they are functional after expansion. They form primary colonies that give rise to secondary colonies, each yielding more than 10(7) cells after few passages. The number of endothelial cells obtained from one unit of CB is compatible with potential clinical application. EPC colonies can be securely produced, expanded and cryopreserved in close culture devices and endothelial cells produced in these conditions are functional as shown in different in vitro and in vivo assays. As CB EPC-derived endothelial cells would be allogeneic to patients, it would be of interest to prepare them from ready-existing CB banks. We show that not all frozen CB units from a CB bank are able to generate EPC colonies in culture, and when they do so, number of colonies is lower than that obtained with fresh CB units. However, endothelial cells derived from frozen CB have the same phenotypical and functional properties than those derived from fresh CB. This indicates that CB cryopreservation should be improved to preserve integrity of stem cells other than haematopoietic ones. Feasibility of using CB for clinical applications will be validated in porcine models of ischaemia.

  6. Endothelial progenitor cell differentiation using cryopreserved, umbilical cord blood-derived mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    Jun-ho JANG; Hugh C KIM; Sun-kyung KIM; Jeong-eun CHOI; Young-jin KIM; Hyun-woo LEE; Seok-yun KANG; Joon-seong PARK; Jin-hyuk CHOI; Ho-yeong LIM

    2007-01-01

    Aim: To investigate the endothelial differentiation potentiality of umbilical cord blood (UCB), we induced the differentiation of endothelial progenitor cells (EPC)from cryopreserved UCB-derived mononuclear cells (MNC). Methods: MNC from cryopreserved UCB and peripheral blood (PB) were cultured in M199 medium with endothelial cell growth supplements for 14 d. EPC were characterized by RT-PCR,flow cytometry, and immunocytochemistry analysis. The proliferation of differen-tiated EPC was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTI') assay, and vascular endothelial growth factor (VEGF) concentra-tion was measured using an ELISA kit. Characteristics of UCB-derived EPC were compared with those of PB-derived EPC. Results: A number of round-shaped cells were loosely attached to the bottom after 24 h culture, and numerous spindle-shaped cells began to appear from the round-shaped ones on d 7. Those cells expressed endothelial markers such as, Fit-1/VEGFR-1, ecNOS, VE-cadherin, yon Willebrand factor, and secreted VEGF. The patterns of endothelial markers of EPC from PB and UCB did not show striking differences. The results of the prolifera-tion and secretion of VEGF were also similar. Conclusion: We successfully cul-tured UCB cells stored at -196 ℃ into cells with the quality of endothelial cells.Those EPC could be used for angiogenic therapeutics by activating adjacent endothelial cells and enhancing angiogenesis.

  7. Functional expression of CD95/Fas Antigen and Bcl-2 on Cord blood Hematopoietic Progenitor Cells

    Institute of Scientific and Technical Information of China (English)

    马艳萍; 邹萍

    2002-01-01

    The cell-surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34+ cells freshly isolated from CB displayed low CD95 expression. The combinations of cytokines such as SCF+FL could up-regulate the expression of CD95 in vitro culture and tumor necrosis factor-e (TNF-α) and interon-γ (IFN-γ) further increased the CD95 expression induced by positive cytokines. The functional status of CD95-mediated apoptosis were analyzed by incubation of CD34+CB cells in the presence of anti-CD95 monoclonal antibodies (McAbs). The effects of anti-CD95 McAbs were measured by viable cell counting, flow cytometry, LTIC and CFU-C assays. A decrease of viable cells, CFUC and LTIC numbers were observed in the presence of anti-CD95 McAbs and TNF-α or IFN-γ.However, growth factor deprivation or the early-acting cytokine such as SCF and FL cross-linking to CD95 caused low apoptosis of CD34+ cells. The correlation of increased intracytoplasmic levels of bcl2 and the presence of CD95 on fresh CB CD34+ cells suggested that bcl-2 might be involved in protecting against CD95-mediated apoptosis of CB CD34+ cells.

  8. 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

  9. Study on the induction and differentiation of megakaryocyte progenitor cell derived from umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    陈琳

    2014-01-01

    Objective To build a protocol of separation and induction of megakaryocytes derived from cord blood mononuclear cells.Methods Red blood cells were precipitated by hydroxyethyl starch(HES).Mononuclear cells were obtained by density gradient centrifugation with Ficoll.The inducing efficiencies of megakaryocytes using different cytokine cocktails and culture media were analyzed.Results The best choice for erythrocyte sedimenta-

  10. Collagen-Coated Polytetrafluoroethane Membrane Inserts Enhances Chondrogenic Differentiation of Human Cord Blood Multi-Lineage Progenitor Cells

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael;

    Background: Articular chondrocytes and bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the favoured cells for cartilage tissue engineering. Umbilical cord blood has proven an alternative source of MSCs and moreover they may be more potent chondroprogenitor cells than bonemarrow...... MSCs. Purpose / Aim of Study: Multilineage progenitor cells (MLPCs) are clonal cord blood-derived MSCs and may therefore provide a cell source with more reproducible outcomes compared to heterogeneous primary MSC cultures. Materials and Methods: We evaluated the chondrogenic potency of MLPCs...... in standard micromass pellet system, layered on calcium polyphosphate (CPP), and on semi-permeable polytetrafluoroethane membranes with and without collagen type I, II or IV pre-coating. Findings / Results: The MPLC cell line used in this study possessed poor chondrogenic potency overall, but membrane...

  11. Intracellular Immunization of Human Fetal Cord Blood Stem/Progenitor Cells with a Ribozyme Against Human Immunodeficiency Virus Type 1

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    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.

  12. Hypoxia Enhances Chondrogenic Differentiation of Human Cord Blood Multilineage Progenitor Cells Seeded on a Novel Scaffold of Freeze Dried Polycaprolactone

    DEFF Research Database (Denmark)

    Munir, Samir; Figueroa, Ryan Jude; Koch, Thomas Gadegaard

    Background Cartilage defects are common and causes osteoarthritis. Articular chondrocytes or bone marrow-derived stromal cells are presently the favoured cells for cartilage tissue engineering. Human umbilical cord blood multilineage progenitor cells (MLPCs) are easily harvested and have capability...... blue. Sulphated glycosaminoglycans (sGAG) and secreted CD-RAP were assessed as markers of cartilage anabolism. Results MLPCs pellets and scaffolds induced in 5% O2 showed increased cellularity and matrix deposition compared with induction in 21% O2. Matrix deposition in pellets was observed in a zonal...

  13. Isolation of human umbilical cord blood aldehyde dehydrogenase-expressing progenitor cells that modulate vascular regenerative functions in vitro and in vivo.

    Science.gov (United States)

    Putman, David M; Hess, David A

    2013-01-01

    This unit describes the isolation and application of human umbilical cord blood progenitor cells to modulate vascular regenerative functions using in vitro co-culture systems and in vivo transplantation models. Using aldehyde dehydrogenase as a marker of stem cell function, blood-derived progenitors can be efficiently purified form human umbilical cord blood using flow cytometry. We describe in vitro approaches to measure cell-mediated effects on the survival, proliferation, and tube-forming function of endothelial cells using growth-rate assays and Matrigel tube-forming assays. Additionally, we provide a detailed protocol for inducing acute unilateral hindlimb ischemia in immune-deficient mice to assess progenitor cell-modulated effects on vascular regeneration by tracking the recovery of blood flow using noninvasive laser Doppler perfusion imaging. Collectively, we present combined in vitro and in vivo transplantation strategies for the pre-clinical assessment of human progenitor cell-based therapies to treat ischemic disease.

  14. Negative selection by apoptosis enriches progenitors in naïve and expanded human umbilical cord blood grafts.

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    Mizrahi, K; Ash, S; Peled, T; Yaniv, I; Stein, J; Askenasy, N

    2014-07-01

    The influence of TNF-α and Fas-ligand (FasL) on viability and function was evaluated in fresh- and expanded-umbilical cord blood (UCB) cells. CD34(+) progenitors and T cells display outstanding survival, whereas ~30% and >50% B lymphocytes and myeloid cells undergo spontaneous apoptosis within 24 and 48 h, respectively. Although the impact of exposure to toxic doses of FasL and TNF-α was undetectable in measurements of apoptosis; removal of dead cells after 2 days of incubation with the ligands revealed a twofold increase in frequency of colony-forming cells (CFU). The sensitivity of progenitors to apoptosis was also unaffected by Fas cross-linking following TNF-induced upregulation of the receptor, increasing CFU frequency without impairing SCID repopulating cell (SRC) activity. Most significant enrichment in CD34(+) progenitors and corresponding increase in CFU frequency were observed when FasL was applied during the final week of ex vivo expansion under the influence of nicotinamide, without impairing SRC activity. These data emphasize differential sensitivities of UCB progenitors and lineage-positive cells to apoptotic signaling mediated by the Fas and TNF receptors, which might be useful in improving the efficiency of ex vivo expansion and improving UCB cell engraftment.

  15. Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells.

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    Butler, Jason M; Gars, Eric J; James, Daylon J; Nolan, Daniel J; Scandura, Joseph M; Rafii, Shahin

    2012-08-09

    Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that coculture of CD34(+) hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45(+)CD34(+) progenitor cells, and 23-fold expansion of CD45(+) Lin(-)CD34(hi+)CD45RA(-)CD49f(+) stem and progenitor cells over a 12-day period. Compared with cytokines alone, coculture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders.

  16. Cord-Blood Banking

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    ... to Be Smart About Social Media Cord-Blood Banking KidsHealth > For Parents > Cord-Blood Banking Print A ... for you and your family. About Cord-Blood Banking Cord-blood banking basically means collecting and storing ...

  17. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H

    2000-01-01

    CXC chemokine receptor 3 (CXCR3), which is known to be expressed predominately on memory and activated T lymphocytes, is a receptor for both interferon gamma (IFN-gamma)-inducible protein 10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report the novel finding that CXCR3 is also...... expressed on CD34(+) hematopoietic progenitors from human cord blood stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) but not on freshly isolated CD34(+) progenitors. Freshly isolated CD34(+) progenitors expressed low levels of CXCR3 messenger RNA, but this expression was highly up...... for the physiologic and pathophysiologic events of differentiation of CD34(+) hematopoietic progenitors into lymphoid and myeloid stem cells, subsequently immune and inflammatory cells. These processes include transmigration, relocation, differentiation, and maturation of CD34(+) hematopoietic progenitors. (Blood...

  18. Interactions of monocyte subpopulations generated from cord blood CD34(+) hematopoietic progenitors with tumor cells: assessment of antitumor potential.

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    Stec, Malgorzata; Baran, Jaroslaw; Szatanek, Rafal; Mytar, Bozenna; Baj-Krzyworzeka, Monika; Gozdzik, Jolanta; Siedlar, Maciej; Zembala, Marek

    2012-11-01

    Monocytes and their subsets (CD14(++)CD16(+) and CD14(+)CD16(-)) generated from cord blood CD34(+) progenitor cells were used for determination of their capacity to interact with tumor cells in vitro and in vivo. The studies in vitro included adhesion to human umbilical vein endothelial cells, cytotoxicity, production of toxic mediators: reactive oxygen and nitrogen intermediates (ROI and RNI, respectively), and finally their effect on transplantable human tumor growth in nonobese diabetic severe combined immunodeficient mice. The CD14(++)CD16(+) subset exhibited an increased adherence to human umbilical vein endothelial cells and cytotoxicity toward tumor cells in vitro. CD14(+)CD16(-) monocytes showed a higher production of reactive oxygen and nitrogen intermediates after stimulation with tumor cells, and more pronounced inhibition of tumor growth in vivo. The results revealed significant differences in the behavior of CD14(++)CD16(+) and CD14(+)CD16(-) monocyte subsets toward tumor cells, thus providing further evidence that CD34(+) cell-derived monocytes differ in this respect from blood monocytes. The protocol for generation of monocytes with antitumor reactivity described here may be useful to obtain monocytes from CD34(+) progenitor cells of cancer patients. This might offer a basis for a novel approach for various forms of cellular immunotherapy of cancer.

  19. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Directory of Open Access Journals (Sweden)

    Katsuhiro Kita

    2011-01-01

    Full Text Available Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation.

  20. Expansion of Umbilical Cord Blood Aldehyde Dehydrogenase Expressing Cells Generates Myeloid Progenitor Cells that Stimulate Limb Revascularization.

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    Putman, David M; Cooper, Tyler T; Sherman, Stephen E; Seneviratne, Ayesh K; Hewitt, Mark; Bell, Gillian I; Hess, David A

    2017-07-01

    Uncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH(hi) cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDH(hi) cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (18-fold over 6-days under serum-free conditions. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, only 15.1% ± 1.3% of progeny maintained high ALDH-activity after culture. However, compared to fresh UCB cells, expansion increased the total number of ALDH(hi) cells (2.7-fold), CD34(+) /CD133(+) cells (2.8-fold), and hematopoietic colony forming cells (7.7-fold). Remarkably, injection of expanded progeny accelerated recovery of perfusion and improved limb usage in immunodeficient mice with femoral artery ligation-induced limb ischemia. At 7 or 28 days post-transplantation, mice transplanted with expanded ALDH(hi) cells showed augmented endothelial cell proliferation and increased capillary density compared to controls. Expanded cells maintained pro-angiogenic mRNA expression and secreted angiogenesis-associated growth factors, chemokines, and matrix modifying proteins. Coculture with expanded cells augmented human microvascular endothelial cell survival and tubule formation under serum-starved, growth factor-reduced conditions. Expanded UCB-derived ALDH(hi) cells represent an alternative to autologous bone marrow as an accessible source of pro-angiogenic hematopoietic progenitor cells for the refinement of vascular regeneration-inductive therapies. Stem Cells Translational Medicine 2017;6:1607-1619. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  1. A method for enriching myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from human cord blood by accessory cell depletion.

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    Dowton, L A; Ma, D D

    1992-10-01

    Human cord blood provides a convenient alternative to bone marrow as a rich source of hemopoietic progenitor cells. This study reports a simple means for enriching a cord blood progenitor cell population by accessory cell depletion. Two methods of monocyte depletion were tested. A Cytodex 3 microcarrier system using collagen coated dextran beads was compared to the more commonly used method of plastic plate adhesion. The method of plastic plate adhesion gave a significantly higher cell recovery. T cell depletion using a recently characterized rat monoclonal antibody which fixes human complement was also investigated. A combined method of monocyte depletion by plate adhesion and T cell depletion resulted in the removal of > 96% of monocytes and > 98% of T cells. This led to a significant enrichment of myeloid (CFU-GM) and erythroid (BFU-E) colony growth. Such enriched progenitor cell populations provide a useful starting population for any study on hemopoiesis.

  2. Histone Deacetylase (HDAC Inhibitors Down-Regulate Endothelial Lineage Commitment of Umbilical Cord Blood Derived Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Horia Maniu

    2012-11-01

    Full Text Available To test the involvement of histone deacetylases (HDACs activity in endothelial lineage progression, we investigated the effects of HDAC inhibitors on endothelial progenitors cells (EPCs derived from umbilical cord blood (UCB. Adherent EPCs, that expressed the endothelial marker proteins (PCAM-1, CD105, CD133, and VEGFR2 revealed by flow cytometry were treated with three HDAC inhibitors: Butyrate (BuA, Trichostatin A (TSA, and Valproic acid (VPA. RT-PCR assay showed that HDAC inhibitors down-regulated the expression of endothelial genes such as VE-cadherin, CD133, CXCR4 and Tie-2. Furthermore, flow cytometry analysis illustrated that HDAC inhibitors selectively reduce the expression of VEGFR2, CD117, VE-cadherin, and ICAM-1, whereas the expression of CD34 and CD45 remained unchanged, demonstrating that HDAC is involved in endothelial differentiation of progenitor cells. Real-Time PCR demonstrated that TSA down-regulated telomerase activity probably via suppression of hTERT expression, suggesting that HDAC inhibitor decreased cell proliferation. Cell motility was also decreased after treatment with HDAC inhibitors as shown by wound-healing assay. The balance of acethylation/deacethylation kept in control by the activity of HAT (histone acetyltransferases/HDAC enzymes play an important role in differentiation of stem cells by regulating proliferation and endothelial lineage commitment.

  3. A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity.

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    Oriane Guillevic

    Full Text Available Endothelial Colony Forming Cells (ECFCs, a distinct population of Endothelial Progenitor Cells (EPCs progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile.

  4. Hypoxia/hypercapnia-induced adaptation maintains functional capacity of cord blood stem and progenitor cells at 4°C.

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    Vlaski, Marija; Negroni, Luc; Kovacevic-Filipovic, Milica; Guibert, Christelle; Brunet de la Grange, Philippe; Rossignol, Rodrigue; Chevaleyre, Jean; Duchez, Pascale; Lafarge, Xavier; Praloran, Vincent; Schmitter, Jean-Marie; Ivanovic, Zoran

    2014-12-01

    We analyzed the effect of exposure to hypoxic/hypercapnic (HH) gas mixture (5% O2 /9% CO2 ) on the maintenance of functional cord blood CD34(+) hematopoietic stem and progenitor cells in severe hypothermia (4°C) employing the physiological and proteomic approaches. Ten-day exposure to HH maintained the Day 0 (D-0) level of hematopoietic stem cells as detected in vivo on the basis of hematopoietic repopulation of immunodeficient mice-short-term scid repopulating cells (SRC). Conversely, in the atmospheric air (20% O2 /0.05% CO2 ), usual condition used for cell storage at 4°C, stem cell activity was significantly decreased. Also, HH doubled the survival of CD34(+) cells and committed progenitors (CFCs) with respect to the atmospheric air (60% vs. 30%, respectively). Improved cell maintenance in HH was associated with higher proportion of aldehyde dehydrogenase (ALDH) positive cells. Cell-protective effects are associated with an improved maintenance of the plasma and mitochondrial membrane potential and with a conversion to the glycolytic energetic state. We also showed that HH decreased apoptosis, despite a sustained ROS production and a drop of ATP amount per viable cell. The proteomic study revealed that the global protein content was better preserved in HH. This analysis identified: (i) proteins sensitive or insensitive to hypothermia irrespective of the gas phase, and (ii) proteins related to the HH cell-protective effect. Among them are some protein families known to be implicated in the prolonged survival of hibernating animals in hypothermia. These findings suggest a way to optimize short-term cell conservation without freezing.

  5. Clinical-scale expansion of CD34(+) cord blood cells amplifies committed progenitors and rapid scid repopulation cells.

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    Casamayor-Genescà, Alba; Pla, Arnau; Oliver-Vila, Irene; Pujals-Fonts, Noèlia; Marín-Gallén, Sílvia; Caminal, Marta; Pujol-Autonell, Irma; Carrascal, Jorge; Vives-Pi, Marta; Garcia, Joan; Vives, Joaquim

    2017-03-25

    Umbilical cord blood (UCB) transplantation is associated with long periods of aplastic anaemia. This undesirable situation is due to the low cell dose available per unit of UCB and the immaturity of its progenitors. To overcome this, we present a cell culture strategy aimed at the expansion of the CD34(+) population and the generation of granulocyte lineage-committed progenitors. Two culture products were produced after either 6 or 14days of in vitro expansion, and their characteristics compared to non-expanded UCB CD34(+) controls in terms of phenotype, colony-forming activity and multilineage repopulation potential in NOD-scid IL2Rγ(null) mice. Both expanded cell products maintained rapid SCID repopulation activity similar to the non-expanded control, but 14-day cultured cells showed impaired long term SCID repopulation activity. The process was successfully scaled up to clinically relevant doses of 89×10(6) CD34(+) cells committed to the granulocytic lineage and 3.9×10(9) neutrophil precursors in different maturation stages. Cell yields and biological properties presented by the cell product obtained after 14days in culture were superior and therefore this is proposed as the preferred production setup in a new type of dual transplant strategy to reduce aplastic periods, producing a transient repopulation before the definitive engraftment of the non-cultured UCB unit. Importantly, human telomerase reverse transcriptase activity was undetectable, c-myc expression levels were low and no genetic abnormalities were found, as determined by G-banding karyotype, further confirming the safety of the expanded product.

  6. Eltrombopag, a thrombopoietin receptor agonist, enhances human umbilical cord blood hematopoietic stem/primitive progenitor cell expansion and promotes multi-lineage hematopoiesis

    OpenAIRE

    2012-01-01

    Umbilical cord blood (UCB) transplantation has emerged as promising therapy, but is challenged by scarcity of stem cells. Eltrombopag is a non-peptide, thrombopoietin (TPO) receptor agonist, which selectively activates c-Mpl in humans and chimpanzees. We investigated eltrombopag’s effects on human UCB hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) expansion, and its effects on hematopoiesis in vivo. Eltrombopag selectively augmented the expansion of human CD45+, CD34+, ...

  7. Clinical-scale cultures of cord blood CD34(+) cells to amplify committed progenitors and maintain stem cell activity.

    Science.gov (United States)

    Ivanovic, Zoran; Duchez, Pascale; Chevaleyre, Jean; Vlaski, Marija; Lafarge, Xavier; Dazey, Bernard; Robert-Richard, Elodie; Mazurier, Frédéric; Boiron, Jean-Michel

    2011-01-01

    We developed a clinical-scale cord blood (CB) cell ex vivo procedure to enable an extensive expansion of committed progenitors--colony-forming cells (CFCs) without impairing very primitive hematopoietic stem cells (HSCs). CD34(++) cells, selected from previously cryopreserved and thawed CB units, were cultured in two steps (diluted 1:4 after 6 days) in the presence of stem cell factor (SCF), fms-related tyrosine kinase 3 ligand (Flt-3L), megakaryocyte growth and development factor (MGDF) (100 ng/ml each), granulocyte-colony stimulating factor (G-CSF) (10 ng/ml) in HP01 serum-free medium. HSC activity was evaluated in a serial transplantation assay, by detection of human cells (CD45, CD33, CD19 and CFC of human origin) in bone marrow (BM) of primary and secondary recipient NOD/SCID mice 6-8 weeks after transplantation. A wide amplification of total cells (∼350-fold), CD34(+) cells (∼100-fold), and CFC (∼130-fold) without impairing the HSC activity was obtained. The activity of a particular HSC subpopulation (SRC(CFC)) was even enhanced.Thus, an extensive ex vivo expansion of CFCs is feasible without impairing the activity of HSCs. This result was enabled by associating antioxidant power of medium with an appropriate cytokine cocktail (i.e., mimicking physiologic effects of a weak oxygenation in hematopoietic environment).

  8. Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE

    Directory of Open Access Journals (Sweden)

    Hassan Rafieemehr

    2015-11-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. The aim of this study was to investigate the neuroprotective effects of transplanted human umbilical cord blood mesenchymal stromal cells (UCB-MSC derived neural progenitor cell (MDNPC in EAE, an experimental model of MS. To initiate neuronal differentiation of UCB-MSCs, the pre-induction medium was removed and replaced with induction media containing retinoic acid, b FGF, h EGF, NGF, IBMX and ascorbic acid for one week. The expression of neural genes was examined in comparison to control group by real-time PCR assay. Then, experimental autoimmune encephalitis (EAE was induced using myelin oligodendrocyte glycoprotein (MOG, 35-55 peptides in 24 C57BL/6 mice. After induction, the mice were divided in four groups (n=6 as follows: healthy, PBS, UCB-MSCs and MDNPC, respectively. At the end of the study, disease status in all the groups was analyzed using hematoxylin-eosin (H&E staining of brain sections. We found that UCB-MSCs exhibit neuronal differentiation potential in vitro and transplanted MDNPC lowered clinical score and reduced CNS leukocyte infiltration compared to untreated mice. Our results showed that MDNPC from UCB may be a proper candidate for regenerative therapy in MS and other neurodegenerative diseases. 

  9. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  10. Preliminary evaluation of treatment efficacy of umbilical cord blood-derived mesenchymal stem cell-differentiated cardiac pro-genitor cells in a myocardial injury mouse model

    Directory of Open Access Journals (Sweden)

    Truc Le-Buu Pham

    2015-12-01

    Full Text Available Recently, stem cell therapy has been investigated as a strategy to prevent or reverse damage to heart tissue. Although the results of cell transplantation in animal models and patients with myocardial ischemia are promising, the selection of the appropriate cell type remains an issue that requires consideration. In this study, we aimed to evaluate the effect of cardiac progenitor cell transplantation in a mouse model of myocardial ischemia. The cardiac progenitor cells used for transplantation were differentiated from umbilical cord blood mesenchymal stem cells. Animal models injected with phosphate-buffered saline (PBS and healthy mice were used as controls. Cell grafting was assessed by changes in blood pressure and histological evaluation. After 14 days of transplantation, the results demonstrated that the blood pressure of transplanted mice was stable, similar to healthy mice, whereas it fluctuated in PBS-injected mice. Histological analysis showed that heart tissue had regenerated in transplanted mice, but remained damaged in PBS-injected mice. Furthermore, trichrome staining revealed that the transplanted mice did not generate significant amount of scar tissue compared with PBS-injected control mice. In addition, the cardiac progenitor cells managed to survive and integrate with local cells in cell-injected heart tissue 14 days after transplantation. Most importantly, the transplanted cells did not exhibit tumorigenesis. In conclusion, cardiac progenitor cell transplantation produced a positive effect in a mouse model of myocardial ischemia. [Biomed Res Ther 2015; 2(12.000: 435-445

  11. Cord blood testing

    Science.gov (United States)

    ... is born. The umbilical cord is the cord connecting the baby to the mother's womb. Cord blood ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  12. Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and progenitor cells: basic principles, experimental approaches, and impact in regenerative medicine.

    Science.gov (United States)

    Flores-Guzmán, Patricia; Fernández-Sánchez, Verónica; Mayani, Hector

    2013-11-01

    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expansion of human UCB-derived HSCs and HPCs has become a priority in the biomedical field. Expansion of progenitor cells can be achieved by culturing such cells in the presence of different combinations of recombinant stimulatory cytokines; in contrast, expansion of actual HSCs has proved to be more difficult because, in addition to needing recombinant cytokines, HSCs seem to deeply depend on the presence of stromal cells and/or elements that promote the activation of particular self-renewal signaling pathways. Hence, there is still controversy regarding the optimal culture conditions that should be used to achieve this. To date, UCB transplants using ex vivo-expanded cells have already been performed for the treatment of different hematological disorders, and although results are still far from being optimal, the advances are encouraging. Recent studies suggest that HSCs may also give rise to nonhematopoietic cells, such as neural, cardiac, mesenchymal, and muscle cells. Such plasticity and the possibility of producing nonhematopoietic cells at the clinical scale could bring new alternatives for the treatment of neural, metabolic, orthopedic, cardiac, and neoplastic disorders. Once standardized, ex vivo expansion of human HSCs/HPCs will surely have a positive impact in regenerative medicine.

  13. Fetal exposure to a diabetic intrauterine environment resulted in a failure of cord blood endothelial progenitor cell adaptation against chronic hypoxia

    Science.gov (United States)

    Dincer, U Deniz

    2015-01-01

    Gestational diabetes mellitus (GDM) has long-term health consequences, and fetal exposure to a diabetic intrauterine environment increases cardiovascular risk for her adult offspring. Some part of this could be related to their endothelial progenitor cells (EPCs). Understanding the vessel-forming ability of human umbilical cord blood (HUCB)-derived endothelial colony-forming cells (ECFCs) against pathological stress such as GDM response to hypoxia could generate new therapeutic strategies. This study aims to investigate the role of chronic hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC was expressed in endothelial and pro-angiogenic specific markers, namely endothelial nitric oxide synthase (eNOS), platelet (PECAM-1) endothelial cell adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell adhesion molecule), vascular endothelial growth factor A, (VEGFA) and insulin-like growth factor 1 (IGF1). Chronic hypoxia did not affect CdH5, but PECAM1 MRNA expressions were increased in control and GDM subjects. Control hypoxic and GDM normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1α) protein expressions were significantly increased in HUCB ECFCs. GDM resulted in most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs’ proliferative ability due to reduction of clonogenic capacity and diminished vessel formation. Furthermore, GDM also resulted in most failure of cord blood ECFC adaptation against chronic hypoxic environment. PMID:25565870

  14. Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings.

    Science.gov (United States)

    Iskander, Asm; Knight, Robert A; Zhang, Zheng Gang; Ewing, James R; Shankar, Adarsh; Varma, Nadimpalli Ravi S; Bagher-Ebadian, Hassan; Ali, Meser M; Arbab, Ali S; Janic, Branislava

    2013-09-01

    Endothelial progenitor cells (EPCs) hold enormous therapeutic potential for ischemic vascular diseases. Previous studies have indicated that stem/progenitor cells derived from human umbilical cord blood (hUCB) improve functional recovery in stroke models. Here, we examined the effect of hUCB AC133+ EPCs on stroke development and resolution in a middle cerebral artery occlusion (MCAo) rat model. Since the success of cell therapies strongly depends on the ability to monitor in vivo the migration of transplanted cells, we also assessed the capacity of magnetic resonance imaging (MRI) to track in vivo the magnetically labeled cells that were administered. Animals were subjected to transient MCAo and 24 hours later injected intravenously with 10(7) hUCB AC133+ EPCs. MRI performed at days 1, 7, and 14 after the insult showed accumulation of transplanted cells in stroke-affected hemispheres and revealed that stroke volume decreased at a significantly higher rate in cell-treated animals. Immunohistochemistry analysis of brain tissues localized the administered cells in the stroke-affected hemispheres only and indicated that these cells may have significantly affected the magnitude of endogenous proliferation, angiogenesis, and neurogenesis. We conclude that transplanted cells selectively migrated to the ischemic brain parenchyma, where they exerted a therapeutic effect on the extent of tissue damage, regeneration, and time course of stroke resolution.

  15. Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus

    Science.gov (United States)

    Hadarits, Orsolya; Zóka, András; Barna, Gábor; Al-Aissa, Zahra; Rosta, Klára; Rigó, János; Kautzky-Willer, Alexandra; Somogyi, Anikó

    2016-01-01

    We assessed the hematopoietic stem and progenitor cell (HSPC) population in the cord blood of neonates born to mothers with gestational diabetes mellitus (GDM) in a hypothesis generating pilot study, due to that, neonatal polycythemia may be the consequence of GDM pregnancy. Forty-five pregnant women with GDM (last trimester mean HbA1C = 33.9 mmol/mol) and 42 (nondiabetic) control pregnant women were enrolled after their routine 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational week (with expected differences in their mean routine clinical characteristics: plasma glucose at OGTT: 0′ = 5.07 vs. 4.62 mM, 120′ = 8.9 vs. 5.76 mM, age = 35.07 vs. 31.66 years, prepregnancy body mass index = 27.9 vs. 23.9 kg/m2, GDM vs. control, respectively) on a voluntary basis after signing the informed consent. EDTA-treated cord blood samples were analyzed by flow cytometry and the software Kaluza1.2 using CD45 and CD34-specific fluorescent antibodies to identify the HSPC population (CD34+ cells within the CD45dim blast gate). The proportion of CD34+CD45dim HSPCs among the nucleated cells was significantly (P < 0.05, statistical power = 60.8%) higher in the cord blood samples of neonates born to mothers with GDM (median 0.38%) compared to neonates born to nondiabetic mothers (median 0.32%) and according to treatment types (P < 0.05) median: control 0.32%, GDM-diet only 0.37%, GDM-on insulin 0.45%; control versus GDM on insulin (P < 0.05). The increased proportion of circulating CD34+CD45dim cells in the cord blood may possibly be related to altered fetal stem cell mobilization in GDM pregnancy, yet these results should be interpreted only as preliminary due to the small sample sizes. PMID:26494027

  16. Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex vivo expansion of CD34+ hematopoietic stem cells and for chondrogenic differentiation

    Institute of Scientific and Technical Information of China (English)

    JIN-FUWANG; LI-JUANWANG; YI-FANWU; YINGXIANG; CHUN-GANGXIE; BING-BINGJIA; JENNYHARRINGTON; IANK.MCNIECE

    2005-01-01

    Background and Objectives. Human mesenchymal stem/progenitor cells (MSPC) ar pluripotent, being the precursors for marrow stroma, bone, cartilage, muscle and connective tissues. Although the presence of hematopoietic stem/progenitor cells (HSPC) in umbilical cord blood (UCB) is well known, that of MSPC has been not fully evaluated. Design and Methods. In this study, we examined the immunophenotype, the supporting function in relation to exvivo expansion of hematopoietic stem progenitor cells and the chondrogenic differentiation of cultured cells with characteristics of MSPC from UCB. When UCB nucleated cells were isolated and 107 cells cultured in IMDM with 20% fetal bovine serum, the mean number of adherent fibroblastlike colonies was 3.5±0.7/106 monuclear cells. Results. UCB-derived MSPC could be expanded for at least 15 passages. In their undifferentiated state, UCB-derived MSPC were CD 13+, CD29+, CD90+, CD105+, CD166+, SH2+,SH3+, SH4+, CD45-, CD34-, and CD14-; they produced stem cell factor, interleukin 6 and tumor necrosis factor α.UCB-derived MSPC cultured in chondrogenic media differentiated into chondrogenic cells. UCB-derived MSPC supported the proliferation and differentiation of CD34+ cells from UCB in vitro. Interpretation and Conclusions. UCB-derived MSPC have the potential to support ex vivo expansion of HSPC and chondrogenic differentiation. UCB should not be regarded as medical waste. It can serve as an alternative source of mesenchymal stem cells and may provide a unique source of fetal cells for cellular and gene therapy.

  17. A comparison of umbilical cord blood-derived endothelial progenitor and mononuclear cell transplantation for the treatment of acute hindlimb ischemia

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2014-01-01

    Full Text Available Acute lower limb ischemia is a common peripheral artery disease whose treatment presents many difficulties. Stem cell transplantation is considered a novel and promising method of treating this disease. Umbilical cord blood (UCB is rich in stem cells, including hematopoietic stem cells (HSCs, mesenchymal stem cells (MSCs and endothelial progenitor cells (EPCs. However, historically, banked umbilical cord blood has been used mainly to treat blood-related diseases. Therefore, this study compared the efficacy of umbilical cord bloodderived mononuclear cells (UCB-MNCs with EPC transplantation for the treatment of acute hindlimb ischemia (ALI in mouse models. MNCs were isolated from UCB by Ficoll gradient centrifugation, after which the EPCs were sorted based on CD34+ and CD133+ markers and cultured according to a previously published protocol. To induce ALI, mice were immuno-suppressed using busulfan (BU and cyclophosphamide (CY, after which the femoral arteries were burned. Induction of ALI in the immune suppressed mice was confirmed by the grade of tissue damage, pedal frequency in water, tissue edema, changes in histology, total white blood cell count, and white blood cell composition. Model mice were injected with a dose of MNCs or EPCs and un-treated control mice were injected with phosphate buffered saline. The efficiency of treatment was evaluated by comparing the grade of tissue damage between the three groups of mice. Mice aged 6 and ndash;12 months were suitable for ALI, with 100% of mice exhibiting ischemia from grade I 10%, grade III 50%, grade IV 40%. For all ALI mice, a gradual increase in pedal frequency in water, increased tissue edema, necrosis of muscle tissue, and loss of hindlimb function were observed after 20 days. Transplanted MNCs and EPCs significantly improved hindlimb ischemia compared with control treatment. Moreover, EPC transplantation significantly improved hindlimb ischemia compared with MNC transplantation. Following

  18. The Role of Amnion Membrane-Derived Mesenchymal Stem Cells on Differentiation and Expansion of Natural Killer Cell Progenitors Originated From Umbilical Cord Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Ahmadi

    2015-11-01

    Full Text Available Background Natural killer (NK cells are members of the innate immune system. Their unique properties, including recognition of viral infected and tumor cells without major histocompatibility complex (MHC restriction or prior sensitization, make them a suitable choice for immunotherapy. Low numbers of NK cells in circulating blood is the most important obstacle for this goal. Objectives The aim of this study was to make an optimum in vitro condition to proliferate and differentiate cord blood (CB-NK cell progenitors to mature NK cells, which can be used for cell therapy. Materials and Methods In our study, CB-Mononuclear Cells’ (MNCs CD3+ lymphocytes were positive depleted using immunomagnetic microbeads. This CD3-depleted (CD3-dep CB - MNCs compartment was used for in vitro expansion with or without a layer of amnion membrane mesenchymal stem cells (MSCs in combination with cytokines that are essential for NK cells expansion (IL-2, IL-3, IL-15, and FLT3 ligand. The expansion period lasted for one week. On day seven, immunophenotype and fold expansion of differentiated cells were measured. Results Combination of cytokines and MSC layer yielded significant fold expansion in comparison with cytokines without feeder conditions (day 7: 5.2 ± 1.12 and 2 ± 0.78, respectively, P < 0.05. CD3-/CD56+ cells percentage increased during the culture period in MSCs/with cytokine and cytokine/without feeder, respectively (day 0: 4.4 ± 0.42% and day 7: 22.9 ± 3.6% and 13.9 ± 1.92 % for MSC/with cytokine and cytokine without feeder, respectively. Conclusions Our results suggested that CB-NK cells progenitors could proliferate and differentiate on feeder layer of amnion membrane MSCs in combination with specific cytokines to produce NK cells for immunotherapy.

  19. Residual expression of the reprogramming factors prevents differentiation of iPSC generated from human fibroblasts and cord blood CD34+ progenitors.

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    Verónica Ramos-Mejía

    Full Text Available Human induced pluripotent stem cells (hiPSC have been generated from different tissues, with the age of the donor, tissue source and specific cell type influencing the reprogramming process. Reprogramming hematopoietic progenitors to hiPSC may provide a very useful cellular system for modelling blood diseases. We report the generation and complete characterization of hiPSCs from human neonatal fibroblasts and cord blood (CB-derived CD34+ hematopoietic progenitors using a single polycistronic lentiviral vector containing an excisable cassette encoding the four reprogramming factors Oct4, Klf4, Sox2 and c-myc (OKSM. The ectopic expression of OKSM was fully silenced upon reprogramming in some hiPSC clones and was not reactivated upon differentiation, whereas other hiPSC clones failed to silence the transgene expression, independently of the cell type/tissue origin. When hiPSC were induced to differentiate towards hematopoietic and neural lineages those hiPSC which had silenced OKSM ectopic expression displayed good hematopoietic and early neuroectoderm differentiation potential. In contrast, those hiPSC which failed to switch off OKSM expression were unable to differentiate towards either lineage, suggesting that the residual expression of the reprogramming factors functions as a developmental brake impairing hiPSC differentiation. Successful adenovirus-based Cre-mediated excision of the provirus OKSM cassette in CB-derived CD34+ hiPSC with residual transgene expression resulted in transgene-free hiPSC clones with significantly improved differentiation capacity. Overall, our findings confirm that residual expression of reprogramming factors impairs hiPSC differentiation.

  20. Eltrombopag, a thrombopoietin receptor agonist, enhances human umbilical cord blood hematopoietic stem/primitive progenitor cell expansion and promotes multi-lineage hematopoiesis.

    Science.gov (United States)

    Sun, Hongliang; Tsai, Ying; Nowak, Irena; Liesveld, Jane; Chen, Yuhchyau

    2012-09-01

    Umbilical cord blood (UCB) transplantation has emerged as a promising therapy, but it is challenged by scarcity of stem cells. Eltrombopag is a non-peptide, thrombopoietin (TPO) receptor agonist, which selectively activates c-Mpl in humans and chimpanzees. We investigated eltrombopag's effects on human UCB hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) expansion, and its effects on hematopoiesis in vivo. Eltrombopag selectively augmented the expansion of human CD45+, CD34+, and CD41+ cells in bone marrow compartment without effects on mouse bone marrow cells in the NOD/SCID mice xenotransplant model. Consequently, eltrombopag increased peripheral human platelets and white blood cells. We further examined effects in the STAT and AKT signaling pathways in serum-free cultures. Eltrombopag expanded human CD34+ CD38-, CD34+, and CD41+ cells. Both eltrombopag and recombinant human TPO (rhTPO) induced phosphorylation of STAT5 of CD34+ CD41-, CD34- CD41+, and CD34- CD41- cells. rhTPO preferentially induced pSTAT3, pAKT, and more pSTAT5 in CD34- C41+ cells, while eltrombopag had no effects on pSTAT3. In conclusion, eltrombopag enhanced expansion of HSCs/HPCs of human UCB in vivo and in vitro, and promoted multi-lineage hematopoiesis through the expansion of bone marrow HSCs/HPCs of human UCB in vivo. Eltrombopag differed somewhat from rhTPO in the signal transduction pathways by favoring earlier HSC/HPC populations.

  1. Cord blood stem cell banking and transplantation.

    Science.gov (United States)

    Dhot, P S; Nair, V; Swarup, D; Sirohi, D; Ganguli, P

    2003-12-01

    Stem cells have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Cord blood as a source of hematopoietic stem cells (HSC) has several advantages as it is easily available, involves non-invasive collection procedure and is better tolerated across the HLA barrier. Since the first cord blood transplant in 1988, over 2500 cord blood HSC transplants have been done world wide. Since then, the advantages of cord blood as a source of hematopietic stem cells for transplantation have become clear. Firstly, the proliferative capacity of HSC in cord blood is superior to that of cells in bone marrow or blood from adults. A 100 ml unit of cord blood contains 1/10th the number of nucleated cells and progenitor cells (CD34+ cells) present in 1000 ml of bone marrow, but because they proliferate rapidly, the stem cell in a single unit of cord blood can reconstitute the entire haematopoietic system. Secondly, the use of cord blood reduces the risk of graft vs host disease. Cord Blood Stem Cell banks have been established in Europe and United States to supply HSC for related and unrelated donors. Currently, more than 65,000 units are available and more than 2500 patients have received transplants of cord blood. Results in children have clearly shown that the number of nucleated cells in the infused cord blood influences the speed of recovery of neutrophils and platelets after myeloablative chemotherapy. The optimal dose is about 2 x 10(7) nucleated cells/kg of body weight. The present study was carried out for collection, separation, enumeration and cryopreservation of cord blood HSC and establishing a Cord Blood HSC Bank. 172 samples of cord blood HSC were collected after delivery of infant prior to expulsion of placenta. The average cord blood volume collected was 101.20 ml. Mononuclear cell count ranged from 7.36 to 25.6 x 10(7)/ml. Viability count of mononuclear cells was 98.1%. After 1 year of cryopreservation, the viability count on

  2. 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.

  3. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Directory of Open Access Journals (Sweden)

    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  4. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Science.gov (United States)

    Perea-Gil, Isaac; Monguió-Tortajada, Marta; Gálvez-Montón, Carolina; Bayes-Genis, Antoni; Borràs, Francesc E.; Roura, Santiago

    2015-01-01

    Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs) with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs). Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ) was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells. PMID:25861626

  5. 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.

  6. Myelotoxicity of trichothecenes and apoptosis: an in vitro study on human cord blood CD34+ hematopoietic progenitor.

    Science.gov (United States)

    Le Dréan, G; Auffret, M; Batina, P; Arnold, F; Sibiril, Y; Arzur, D; Parent-Massin, D

    2005-12-01

    Previous studies have revealed that hematological disorders associated with trichothecenes intoxication in humans could result from hematopoiesis inhibition. The most frequent and potent trichothecene mycotoxins are T-2 toxin and deoxynivalenol (DON), respectively. Apoptosis induction by these two toxins was investigated in vitro on human hematopoietic progenitors (CD34+ cells). Hoechst coloration, DNA fragmentation and annexin-V/PI labeling in flow cytometry showed that T-2 toxin, in contrast to DON, induced apoptosis in CD34+ cells. T-2 toxin effect was dose- and time-dependent with a significant increase of apoptotic cells as early as 3h after incubation at 10(-7) M and a maximum reached at 12 h. This observation evidenced the high sensitivity of hematopoietic progenitors to T-2 toxin. The inhibition of T-2 toxin-induced apoptosis by a pan-caspase inhibitor (Z-VAD-fmk) suggested the involvement of caspases. The proportional increase of caspase-3 specific activity (DEVDase) with T-2 toxin concentration confirmed its role in the process. After incubation of CD34+ cells with T-2 toxin, in conditions that induced apoptosis, clonal expansion of granulo-monocytes, erythrocytes and megakaryocytes precursors was dose-dependently inhibited. The hematological effects observed in T-2 toxin mycotoxicosis could then be assigned to hematopoiesis inhibition by apoptosis. Different mechanisms that need to be further elucidated are involved in DON myelotoxicity.

  7. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H

    2000-01-01

    for the physiologic and pathophysiologic events of differentiation of CD34(+) hematopoietic progenitors into lymphoid and myeloid stem cells, subsequently immune and inflammatory cells. These processes include transmigration, relocation, differentiation, and maturation of CD34(+) hematopoietic progenitors. (Blood......Ab blocked these functions of gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha. gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+) progenitors. Moreover, gamma IP-10 and Mig...

  8. Ex vivo expansion of hematopoietic stem- and progenitor cells from cord blood in coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly, amniotic fluid, cord blood, and bone marrow.

    Science.gov (United States)

    Klein, Caroline; Strobel, Julian; Zingsem, Jürgen; Richter, Richard H; Goecke, Tamme W; Beckmann, Matthias W; Eckstein, Reinhold; Weisbach, Volker

    2013-12-01

    In most cases, the amount of hematopoietic stem and progenitor cells (HSPCs) in a single cord blood (CB) unit is not sufficient for allogenic transplantation of adults. Therefore, two CB units are usually required. The ex vivo expansion of HSPCs from CB in coculture with mesenchymal stroma cells (MSCs) might be an alternative. It was investigated, whether bone marrow-derived MSCs, which have to be obtained in an invasive procedure, introduce a further donor and increases the risk of transmissible infectious diseases for the patient can be replaced by MSCs from amnion, chorion, Wharton's jelly, amniotic fluid, and CB, which can be isolated from placental tissue which is readily available when CB is sampled. In a two-step ex vivo coculture mononuclear cells from cryopreserved CB were cultured with different MSC-feederlayers in a medium supplemented with cytokines (stem cell factor, thrombopoietin [TPO], and granulocyte colony-stimulating factor). Expansion rates were analyzed as well, by long-term culture-initiating cell (LTC-IC) and colony-forming unit (CFU) assays, as by measuring CD34(+)- and CD45(+)-cells. Due to the comparably low number of 5×10(2) to 1×10(4) CD34(+)-cells per cm(2) MSC-monolayer, we observed comparably high expansion rates from 80 to 391,000 for CFU, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. Expansion of LTC-IC was partly observed. Compared to the literature, we found a better expansion rate of CD34(+)-cells with MSCs from all different sources. This is probably due to the comparably low number of 5×10(2) to 1×10 CD34(+)-cells per cm(2) MSC-monolayer we used. Comparably, high expansion rates were observed from 80 to 391,000 for CFUs, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. However, the expansion of CD34(+)-cells was significantly more effective with MSCs from bone marrow compared to MSCs from amnion, chorion, and Wharton's jelly. The comparison of MSCs from bone marrow with MSCs from CB and

  9. Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Edyta Paczkowska

    Full Text Available BACKGROUND: Stem/progenitor cells (SPCs demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs and their receptors in specific umbilical cord blood (UCB SPC populations, including lineage-negative, CD34(+, and CD133(+ cells, with that in unsorted, nucleated cells (NCs. METHODS AND RESULTS: The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+, and CD133(+ cells. To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3 was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+, and CD133(+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+ or CD133(+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. CONCLUSIONS: Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and

  10. Umbilical cord blood transplantation.

    Science.gov (United States)

    Koo, Hong Hoe; Ahn, Hyo Seop

    2012-07-01

    Since the first umbilical cord blood transplantation (CBT) in 1998, cord blood (CB) has now become one of the most commonly used sources of hematopoietic stem cells for transplantation. CBT has advantages of easy procurement, no risk to donor, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite human leukocyte antigen disparity. Several studies have shown that the number of cells transplanted is the most important factor for engraftment in CBT, and it limits the wide use of CB in adult patients. New strategies for facilitating engraftment and reducing transplantation-related mortality are ongoing in the field of CBT and include the use of a reduced-intensity conditioning regimen, double-unit CBT, ex vivo expansion of CB, and co-transplantation of CB and mesenchymal stem cells. Recently, the results of two international studies with large sample sizes showed that CB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack human leukocyte antigen-matched adult donors. Along with the intensive researches, development in banking process of CB will amplify the use of CB and offer the chance for cure in more patients.

  11. Umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Hong Hoe Koo

    2012-07-01

    Full Text Available Since the first umbilical cord blood transplantation (CBT in 1998, cord blood (CB has now become one of the most commonly used sources of hematopoietic stem cells for transplantation. CBT has advantages of easy procurement, no risk to donor, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite human leukocyte antigen disparity. Several studies have shown that the number of cells transplanted is the most important factor for engraftment in CBT, and it limits the wide use of CB in adult patients. New strategies for facilitating engraftment and reducing transplantation-related mortality are ongoing in the field of CBT and include the use of a reduced-intensity conditioning regimen, double-unit CBT, ex vivo expansion of CB, and co-transplantation of CB and mesenchymal stem cells. Recently, the results of two international studies with large sample sizes showed that CB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack human leukocyte antigen-matched adult donors. Along with the intensive researches, development in banking process of CB will amplify the use of CB and offer the chance for cure in more patients.

  12. Procedure for action in the donation of umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Antonio Herrera Gómez

    2012-05-01

    Full Text Available Stem cells are candidates for donation and transplantation in certain diseases, such as treatment of choice. Stem cells from umbilical cord blood are of particular interest as a gift, for many reasons. It should be noted that the umbilical cord blood is a single, limited source of hematopoietic progenitor cells, and the eventual success of a transplant, cellular viability and retained sample are critical, so the extraction process transport and cryopreservation must be performed under strict quality control criteria. Objective: To describe the procedure extacción umbilical cord blood to be carried out in units of delivery, to ensure quality results.

  13. Targeted expansion and regulation of genetically modified cord blood stem/progenitor cells in vitro%靶基因调控的脐血干/祖细胞体外长期扩增与调控

    Institute of Scientific and Technical Information of China (English)

    赵声明; 彭明婷; 顾惜春; 常乃柏

    2008-01-01

    BACKGROUND: Cord blood stem cells are one of ideal target cells for gene therapy, but low gene transferring rate is the main difficulty at recent. Janus kinase tyrosine 2 (JAK2) plays an important role in self-renewing of cord blood stem/progenitor cell12s. Therefore, cord blood CD34+ cell line modified by target-amplified JAK2 genes has been developed yet by using gene regulating expression technique in order to overcome low transferring rate of cord blood genes.OBJECTIVE: To investigate the feasibility and reliability of a long-term amplified regulation for cord blood stem/progenitor cells mediated by transgene JAK2. SETTING: Department of Hematology, Beijing Hospital, Ministry of Health.MATERIALS: The experiment was carried out in the Laboratory of Hematological Department, Beijing Hospital, Ministry of Health from June 2003 to April 2006. Cord blood was derived from umbilical cord which was immediately cut from healthy, full-term and natural-parturition infants and was provided by Department of Obstetrics & Gynecology, Beijing Hospital. The experiment was approved by the local ethical committee, and informed consent was obtained from expectant mothers and their relatives for the use of cord blood cells. MiniMACS magnetic separation apparatus and immunomagnetic beads adsorbing CD34 single antibody were provided by Miltenyi Biotec Company, Germany; flow cytometer by FACScalibur, USA; recombinant human stem cell factor (rhSCF), Flt3 ligand (FL), human interleukin-6 (hIL-6), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and thrombopoeitin (TPO) by PeproTec Company; nude mice of the SPF level by Animal Center of Beijing Medical University.METHODS: Retroviral vector MGI-F2JAK2, which was composed of functional catalytic domain of JAK2 genes and two site proteins (2xF36v, F2) combined with synthetic drug (AP20187) of target gene of small molecules, was constructed. AP20187 might specially combine with F36v to

  14. Percutaneous umbilical cord blood sampling - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100196.htm Percutaneous umbilical cord blood sampling - series—Normal anatomy To use the ... or blood disorder, your doctor may recommend percutaneous umbilical cord blood sampling (PUBS), which is performed at 18 ...

  15. CD133+人脐血造血祖细胞的干性维持培养及鉴定%Long-term culture and identification of CD133 + hematopoietic progenitor cells from human umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    吴小金; 陈芳; 陆滟霞; 杨慧; 彭璠莉; 袁理; 刘国炳; 李学农

    2012-01-01

    Objective To isolate CD133+ hematopoietic progenitor cells from human umbilical cord blood and optimize the culture condition for maintaining their stem cell characteristics. Methods CD133+ hematopoietic progenitor cells were isolated from human umbilical cord blood using magnetic cell sorting system, and the cells were detected by flow cytometry. Four methods were used for culturing cells. After 8 weeks' culture, cytomorphology, flow cytometry, immunocytochemistry and immunofluorescence assay were used to identify the characteristics of the stem cells. Results Over 80% of CD133 * hematopoietic progenitor cells were isolated from human umbilical cord blood using magnetic cell sorting system. The cells were effectively expanded using optimized serum-free medium after 8 weeks of cell culture, whereas the cells in other media differentiated into adherent cells in a poor state. Conclusion The optimized serum-free medium allows effective expansion of CD133+ hematopoietic progenitor cells that maintain stem cell characteristics after a long-term culture.%目的 从人脐带血中分选出CD133+造血祖细胞,并进行长时间干性维持培养.方法 通过免疫磁珠法分选出人脐带血中的CD133+造血祖细胞,经流式细胞仪检测免疫磁珠分选后的CD133+造血祖细胞.采用五种方法扩增培养该细胞,8周后,再通过细胞形态学、流式细胞术、免疫细胞化学和免疫荧光对细胞进行干性鉴定,探索最佳干性维持培养方法.结果 通过免疫磁珠法可以从人脐带血中分选出80%以上的CD133+造血祖细胞.采用优化的无血清培养基培养8周之后,CD133+造血祖细胞可得到有效扩增.而其他的培养基会使CD133+造血祖细胞由半悬浮细胞分化为梭形贴壁细胞,并且细胞状态欠佳.结论 利用免疫磁珠法分选出的CD133+造血祖细胞,采用优化的无血清培养基能够有效扩增该细胞,并可长期有效的维持其干性.

  16. Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

    Directory of Open Access Journals (Sweden)

    Ali Dehghanifard

    2012-07-01

    Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

  17. Cord Blood Transplantation Study (COBLT): cord blood bank standard operating procedures.

    Science.gov (United States)

    Fraser, J K; Cairo, M S; Wagner, E L; McCurdy, P R; Baxter-Lowe, L A; Carter, S L; Kernan, N A; Lill, M C; Slone, V; Wagner, J E; Wallas, C H; Kurtzberg, J

    1998-12-01

    In 1995, the National Heart Lung and Blood Institute (NHLBI) solicited requests for a proposal (RFP) entitled "Transplant Centers for Clinical Research on Transplantation of Umbilical Cord Stem and Progenitor Cells." Three banks, six transplant centers, and one medical coordinating center (MCC) (Table 1) were funded with the overall goal of banking cord blood units (CBU) using a single manual of operations. Furthermore, the clinical protocols to evaluate the transplant outcome for adult and pediatric recipients of these well-characterized CBU would be analyzed in a uniform fashion. Because of the intense interest of the transplantation community in the policies and procedures for cord blood collection and processing, the principal investigators of the cord blood banks (CBB) and NHLBI elected to submit for publication the rationale and an abridged, but detailed, version of the standard operating procedures (SOP) developed between October 1996 and July 1998 prior to the initiation of the clinical protocols to be performed with these CBU. As the SOP will be refined over time, the complete SOP and subsequent amendments will be published and continually updated on the websites from the MCC-The EMMES Corporation (www.EMMES.com). All forms referred to in this document may be obtained from the EMMES website. It is hoped that the publication of this document will lay down a framework that will not only facilitate the development of other CBB but also help us more rapidly define what constitutes an "acceptable" CBU product.

  18. Effect of PolyI:C on Quantity and Activity of Endothelial Progenitor Cells From Human Umbilical Cord Blood%PolyI:C对人脐血内皮祖细胞数量及功能的影响

    Institute of Scientific and Technical Information of China (English)

    杨梅; 肖智林; 吕青山; 陈美芳; 陈晓彬; 谢秀梅; 胡锦跃

    2011-01-01

    目的 观察Toll样受体3的配体聚肌胞(PolyI:C)对人脐血内皮祖细胞增殖、凋亡及炎性细胞因子表达的影响.方法 采用密度梯度离心法获取人脐静脉血单个核细胞,EBM-2细胞培养基进行培养,诱导单个核细胞向内皮祖细胞分化.以不同浓度的PolyI:C(0、0.01、0.1、1 g/L和10 g/L)干预人脐血内皮祖细胞,通过CCK-8细胞增殖试验检测PolyI:C对内皮祖细胞增殖的影响,流式细胞术检测PolyI:C对细胞凋亡的影响.通过逆转录聚合酶链反应对内皮祖细胞表达的Toll样受体进行检测,并检测不同浓度的PolyI:C对内皮祖细胞表达Toll样受体3、炎性细胞因子的影响.结果 静息状态下,内皮祖细胞表达较高水平的Toll样受体1、Toll样受体3、Toll样受体4、Toll样受体6,表达较低水平的Toll样受体2、Toll样受体5、Toll样受体7、Toll样受体8、Toll样受体10,不表达Toll样受体9.而PolyI:C能上调Toll样受体3 mRNA表达,并呈量效关系.与对照组相比,较高浓度PolyI:C(1 g/L和10 g/L)持续作用于脐血内皮祖细胞3天后显著抑制内皮祖细胞增殖(P<0.01),终浓度10 g/L的PolyI:C呈时间依赖性抑制内皮祖细胞增殖,且PolyI:C呈剂量依赖性诱导内皮祖细胞凋亡.同时,PolyI:C呈剂量依赖性上调炎性细胞因子白细胞介素1β、白细胞介素6、白细胞介素8、肿瘤坏死因子α、干扰素β的基因表达.结论 PolyI:C可能通过活化Toll样受体3诱导内皮祖细胞凋亡,从而抑制内皮祖细胞增殖,并促进内皮祖细胞表达相关炎性细胞因子.%Aim To investigate the effect of a synthetic dsRNA analog polyriboinosinic polyribocytidylic acid ( PolyI: C) on quantity and activity of endothelial progenitor cells from human umbilical cord blood in vitro. Methods Mononuclear cells were isolated from human cord blood by Ficoll density gradient centrifugation and then the cells were cultured in EBM-2 medium to differentiate into endothelial

  19. How to improve cord blood engraftment?

    Directory of Open Access Journals (Sweden)

    Meral eBeksac

    2016-02-01

    Full Text Available Various factors make cord blood (CB a significant source of hematopoietic stem cells (HSC, including ease of procurement and lack of donor attrition, with the ability to process and store the donor cells long term. Importantly, high proliferative potential of the immature HSCs allows one log less use of cells compared to bone marrow (BM or peripheral blood stem cells. As total nucleated cell (TNC and CD34 + cell content of CB grafts are correlated with engraftment rate and speed, strategies to expand HSC and homing have been developed. This chapter will focus on modalities such as intra-bone administration, fucosylation, CD26 inhibition, Prostaglandin G2 derivative or complement 3 exposure and SDF-1/CXCR4/CXCL-12 pathway interventions that have been experimented successfully. Furthermore increasing evidence in line with better recognition of CB progenitors that are involved in engraftment and homing will also be addressed.

  20. Imatinib and nilotinib inhibit hematopoietic progenitor cell growth, but do not prevent adhesion, migration and engraftment of human cord blood CD34+ cells.

    Directory of Open Access Journals (Sweden)

    Ludovic Belle

    Full Text Available BACKGROUND: The availability of tyrosine kinase inhibitors (TKIs has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors have shown that therapeutic doses of nilotinib deliver drug levels similar to those of imatinib. The aim of this study was to compare the inhibitory effects of imatinib and nilotinib on proliferation, differentiation, adhesion, migration and engraftment capacities of human cord blood CD34(+ cells. DESIGN AND METHODS: After a 48-hour cell culture with or without TKIs, CFC, LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second time, the impact of these TKIs on engraftment was assessed in a xenotransplantation model using NOD/SCID/IL-2Rγ (null mice. RESULTS: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of CFC formation due to inhibition of CD34(+ cell cycle entry. Adhesion of CD34(+ cells to retronectin was reduced in the presence of either imatinib or nilotinib but only at high concentrations. Migration through a SDF-1α gradient was not changed by cell culture in the presence of TKIs. Finally, bone marrow cellularity and human chimerism were not affected by daily doses of imatinib and nilotinib in a xenogenic transplantation model. No significant difference was seen between TKIs given the equivalent affinity of imatinib and nilotinib for KIT. CONCLUSIONS: These data suggest that combining non-myeloablative conditioning regimen with TKIs starting the day of the transplantation could be safe.

  1. Cord-Blood Banking

    Science.gov (United States)

    ... blood banks may capitalize on the fears of vulnerable new parents by providing misleading information about the statistics of stem cell transplants. Parents of children of ethnic or racial minorities, adopted children, or ...

  2. Effect of human cytomegalovirus on proliferation of hematopoietic progenitor cells of cord blood%人类巨细胞病毒感染对脐血造血祖细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    刘文君; 金润铭; 付晓冬; 刘斌; 郭渠莲; 邓正华

    2006-01-01

    目的探讨人类巨细胞病毒(HCMV)感染对脐血造血祖细胞(CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk)体外增殖的抑制作用及其机制.方法20例脐血标本收集于正常足月顺产新生儿.实验共分5组:(1)3个HCMV感染组,每个感染组分别加入0.1 mL的103、104及105空斑形成单位(PFU)HCMV-AD169病毒液于培养体系中;(2)灭活对照组,加入同体积灭活HCMV病毒液;(3)空白对照组,不加HCMV病毒液,代之以同体积的IMDM.采用造血祖细胞体外半固体培养技术,培养、观察、计数HCMV-AD169株对脐血CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk集落数、抑制率和集落维持时间;并用聚合酶链反应(PCR)技术检测集落细胞内HCMV-DNA.结果(1)在造血祖细胞培养体系中加入不同滴度的HCMV-AD169后,104和105PFU滴度感染对CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk集落形成均有显著的抑制作用,103PFU滴度感染对CFU-Mix及CFU- Mk集落形成有显著的抑制作用,与空白对照组和灭活对照组比较,差异有显著性(P<0.05).病毒滴度越高,抑制程度越明显(P<0.05).(2)104和105 PFU滴度感染组CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk集落维持时间较对照组明显缩短(P<0.01),103 PFU滴度感染组CFU-Mix和CFU-Mk集落维持时间较对照组明显缩短(P<0.01).(3)PCR显示3个感染组的CFU-GM、CFU-E、CFU-Mix及CFU-Mk集落细胞内均有HCMV-AD169 DNA存在.结论HCMV-AD169能直接感染CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk造血祖细胞,并抑制造血祖细胞的增殖,这可能与HCMV感染患儿出现粒细胞减少、血小板减少和贫血等造血功能紊乱有关.%Objective This study was designed to investigate the effect of human cytomegalovirus (HCMV) on the proliferation of colony forming unit granulocyte-macrophage ( CFU-GM ), CFU-erythroid ( CFU-E), burst forming uniterythroid (BFU-E), CFU-multipotential (CFU-Mix) and CFU-megakaryocytic (CFU-Mk) progenitor cells of cord blood in vitro as well as

  3. [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.

  4. Neuromesodermal progenitors and the making of the spinal cord

    Science.gov (United States)

    Henrique, Domingos; Abranches, Elsa; Verrier, Laure; Storey, Kate G.

    2016-01-01

    Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a result of patterning of the anterior neural plate. However, as the molecular mechanisms that specify NMps in vivo are uncovered, and as protocols for generating these bipotent cells from mouse and human pluripotent stem cells in vitro are established, the emerging data suggest that this view needs to be revised. Here, we review the characteristics, regulation, in vitro derivation and in vivo induction of NMps. We propose that these cells arise within primitive streak-associated epiblast via a mechanism that is separable from that which establishes neural fate in the anterior epiblast. We thus argue for the existence of two distinct routes for making central nervous system progenitors. PMID:26329597

  5. Family-directed umbilical cord blood banking

    Science.gov (United States)

    Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M.

    2011-01-01

    Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available. PMID:21750089

  6. 人脐血内皮祖细胞治疗裸鼠心肌梗死%Transplantation of endothelial progenitor cells from human cord blood into ischemic myocardium of nude mice

    Institute of Scientific and Technical Information of China (English)

    董永强; 徐家行; 张晓明; 朱水波; 刘高利; 殷桂林

    2010-01-01

    目的 探讨人脐血内皮祖细胞(EPCs)移植治疗裸鼠心肌梗死的可行性.方法 采用淋巴细胞分离液提取人脐血单个核细胞(MNCs),应用添加诱导因子的培养基于体外诱导分化并于培养7 d后进行鉴定.采用20只裸鼠建立心肌梗死模型后,将体外诱导分化7 d并摄取CM-Dil的内皮祖细胞通过尾静脉注射进行细胞移植到实验组,对照组注射培养基.2周后计数心梗区域新生毛细m管密度及心梗面积并于荧光显微镜下观察新生血管的荧光.结果 体外诱导7 d后贴壁细胞CD34阳性率达(50.48±5.17)%,CDl33阳性率达(19.12±4.37)%.实验组平均梗死面积为(8.27±1.64)%,对照组为(14.30±2.84)%(t=-4.78,P<0.05);实验组每高倍视野平均新生血管密度为14.29±1.38,对照组为10.17±1.72(t=4.71,P<0.01);行荧光显微镜下观察实验组新生血管有红色荧光.讨论人脐血单个核细胞在体外诱导分化为内皮祖细胞,进行细胞移植到建立心梗模型的裸鼠后可在心梗区域形成新生血管,从而并改善梗死部位心脏功能.%Objective To investigate the possibility of endothelial progenitor cells (EPCs) trans-plantation for the treatment of myocardial infarction of nude mice. Methods Mononuclear cells (MNCs) were isolated by lymphocyte separating medium from human cord blood and were cultured in DMEM with proper inducing factors. After 7 days, the attached cells were identified by the characteristic of EPCs. After establishing myocardial infarction model of 20 nude mice the attached cells taking CM-Dil were injected into vena caudalis. The control group was injected with non-serum culture medium, nfarcted size, apillary den-sity and fluorescence of new capillaries were measured 2 weeks after operation. Results After 7 days, the CD34 positive rate in the attached cells was (50.48±5. 17)% and CD133 rate was (19. 12±4. 37)%, respectively. Two weeks after operations, infarcted sizes of transplantation group was

  7. Cord blood banking: 'providing cord blood banking for a nation'.

    Science.gov (United States)

    Querol, Sergio; Rubinstein, Pablo; Marsh, Steven G E; Goldman, John; Madrigal, Jose Alejandro

    2009-10-01

    Transplantation of cord blood (CB) is increasingly used as therapy for patients whose own marrow is affected by genetic mutations that prevent the development of normal cells of the blood or immune tissues, or for patients whose marrow has been destroyed in the course of treatment for leukaemia and other malignancies. CB is a rich source of haematopoietic stem cells, can be easily harvested and stored in frozen aliquots in a CB bank. The first public CB bank was established in 1993 allowing unrelated CB transplantation to become an option for patients lacking a suitable adult donor. Today, the results of CB transplantation are comparable to those of bone marrow transplants with several important advantages: the graft is available 'off the shelf', thereby reducing the waiting time, and the requirements of human lecucoyte antigen (HLA) matching are less restrictive than those of adult sources. The reduced requirement for HLA matching allows transplants between incompletely matched donors and recipients, thus reducing the size of the inventory required at the national level. This also mitigates the disadvantage encountered by persons of rare HLA genotypes or those who do not belong to populations of North Western European descent. Finally, national CB programmes can easily make available for research individual surplus units not meeting minimal criteria for clinical use.

  8. Short-Lived Human Umbilical Cord-Blood-Derived Neural Stem Cells Influence the Endogenous Secretome and Increase the Number of Endogenous Neural Progenitors in a Rat Model of Lacunar Stroke.

    Science.gov (United States)

    Jablonska, Anna; Drela, Katarzyna; Wojcik-Stanaszek, Luiza; Janowski, Miroslaw; Zalewska, Teresa; Lukomska, Barbara

    2016-11-01

    Stroke is the leading cause of severe disability, and lacunar stroke is related to cognitive decline and hemiparesis. There is no effective treatment for the majority of patients with stroke. Thus, stem cell-based regenerative medicine has drawn a growing body of attention due to the capabilities for trophic factor expression and neurogenesis enhancement. Moreover, it was shown in an experimental autoimmune encephalomyelitis (EAE) model that even short-lived stem cells can be therapeutic, and we have previously observed that phenomenon indirectly. Here, in a rat model of lacunar stroke, we investigated the molecular mechanisms underlying the positive therapeutic effects of short-lived human umbilical cord-blood-derived neural stem cells (HUCB-NSCs) through the distinct measurement of exogenous human and endogenous rat trophic factors. We have also evaluated neurogenesis and metalloproteinase activity as cellular components of therapeutic activity. As expected, we observed an increased proliferation and migration of progenitors, as well as metalloproteinase activity up to 14 days post transplantation. These changes were most prominent at the 7-day time point when we observed 30 % increases in the number of bromodeoxyuridine (BrdU)-positive cells in HUCB-NSC transplanted animals. The expression of human trophic factors was present until 7 days post transplantation, which correlated well with the survival of the human graft. For these 7 days, the level of messenger RNA (mRNA) in the analyzed trophic factors was from 300-fold for CNTF to 10,000-fold for IGF, much higher compared to constitutive expression in HUCB-NSCs in vitro. What is interesting is that there was no increase in the expression of rat trophic factors during the human graft survival, compared to that in non-transplanted animals. However, there was a prolongation of a period of increased trophic expression until 14 days post transplantation, while, in non-transplanted animals, there was a

  9. CD34+ stem cells from umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Alfio D’Agati

    2011-09-01

    Full Text Available We describe the relation between umbilical cord clamping time and two different enrichment system of CD34+ stem cells from umbilical cord blood with the proliferative ability and bone marrow reconstitution of the stem cells obtained. After an obstetrician performed the cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections using the Stem Sep method, or with a positive cells selection based on their surface CD34 antigens using the Mini Macs system. An excellent recovery of haematopoietic progenitors [Burst Forming Unit Erythroids (BFUE; Colony Forming Unit Granulocytes and Macrophages (CFU-GM; and Colony Forming Unit Granulocytes, Erythroids, Monocytes and Macrophages (CFU-GME], inversely related to the increase in clamping time, was performed with the Mini Macs system (54% of colonies, with 90% purity. With Stem Sep method, haematopoietic progenitor’s recovery was 35% (with 80% purity. By applying early clamping of umbilical cord blood we obtained a greater number of CD34+ cells and their clonogenic activity was increased with enrichment. This is a useful technique considering that the number of CD34+ stem cells usually contained from a unit of placental blood is enough for the transplant to a child, but not for an adult. Thus, using these methods, we can get a larger number of CD34+ stem cells which reduces the risk of Graft versus Host Disease also in adult patients, producing survival rates similar to those obtained with transplantation of bone marrow from unrelated donors.

  10. CD34+ stem cells from umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Carlo Pafumi

    2011-10-01

    Full Text Available We describe the relation between umbilical cord clamping time and two different enrichment system of CD34+ stem cells from umbilical cord blood with the proliferative ability and bone marrow reconstitution of the stem cells obtained. After an obstetrician performed the cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections using the Stem Sep method, or with a positive cells selection based on their surface CD34 antigens using the Mini Macs system. An excellent recovery of haematopoietic progenitors [Burst Forming Unit Erythroids (BFUE; Colony Forming Unit Granulocytes and Macrophages (CFU-GM; and Colony Forming Unit Granulocytes, Erythroids, Monocytes and Macrophages (CFU-GME], inversely related to the increase in clamping time, was performed with the Mini Macs system (54% of colonies, with 90% purity. With Stem Sep method, haematopoietic progenitor’s recovery was 35% (with 80% purity. By applying early clamping of umbilical cord blood we obtained a greater number of CD34+ cells and their clonogenic activity was increased with enrichment. This is a useful technique considering that the number of CD34+ stem cells usually contained from a unit of placental blood is enough for the transplant to a child, but not for an adult. Thus, using these methods, we can get a larger number of CD34+ stem cells which reduces the risk of Graft versus Host Disease also in adult patients, producing survival rates similar to those obtained with transplantation of bone marrow from unrelated donors.

  11. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish.

    Directory of Open Access Journals (Sweden)

    Subhra Prakash Hui

    Full Text Available Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.

  12. Isolation of mesenchymal stem cells from equine umbilical cord blood

    OpenAIRE

    Thomsen Preben D; Heerkens Tammy; Koch Thomas G; Betts Dean H

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is lo...

  13. Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic?

    Science.gov (United States)

    Norkin, M; Lazarus, H M; Wingard, J R

    2013-07-01

    Umbilical cord blood (UCB) is an attractive stem cell graft option for patients who need allogeneic hematopoietic stem cell support, but lack a suitable HLA-matched donor. However, the limited number of hematopoietic progenitor cells in a single cord blood unit can lead to an increased risk of graft failure, delayed hematological recovery and prolonged immunosuppression, particularly in adult patients. Several strategies to overcome these potential limitations are being evaluated. In this review, we discuss promising ex vivo manipulations to enhance cord blood engraftment capacity such as culture of UCB cells with stimulatory cytokines and growth factors, mesenchymal cells, Notch ligand, copper chelators, prostaglandins, complement components, nicotinamide and CD26/DPPIV inhibitors. All these approaches are now in early clinical trials. However, despite the fact that several cord blood enhancement strategies have resulted in increased numbers of progenitor cells and faster neutrophil recovery, the ability of these techniques to significantly shorten engraftment time and permit the use of cord units with low numbers of total nucleated cells, or accomplish reliable engraftment with a single cord, have yet to be convincingly demonstrated. The ultimate clinical value of ex vivo cord blood expansion or manipulation has not been defined yet, and the current data do not permit predicting which technology will prove to be the optimal strategy. Nevertheless, expectations remain high that eventually ex vivo enhancement will be able to improve clinical outcomes and significantly extend the applicability of UCB transplantation.

  14. Temporal response of endogenous neural progenitor cells following injury to the adult rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yilin eMao

    2016-03-01

    Full Text Available A pool of endogenous neural progenitor cells found in the ependymal layer and the sub-ependymal area of the spinal cord are reported to upregulate nestin in response to traumatic spinal cord injury. These cells could potentially be manipulated within a critical time period offering one innovative approach to the repair of spinal cord injury. However, little is known about the temporal response of endogenous neural progenitor cells following spinal cord injury. This study used a mild contusion injury in rat spinal cord and immunohistochemistry to determine the temporal response of ependymal neural progenitor cells following injury and their correlation to astrocyte activation at the lesion site. The results from the study demonstrated that Nestin staining intensity at the central canal peaked at 24 hours post-injury and then gradually declined over time. Reactive astrocytes double labelled by Nestin and GFAP were found at the lesion edge and commenced to form the glial scar from 1 week after injury. We conclude that the critical time period for manipulating endogenous neural progenitor cells following a spinal cord injury in rats is between 24 hrs when nestin expression in ependymal cells is increased and 1 week when astrocytes are activated in large numbers.

  15. Ethical considerations in umbilical cord blood banking.

    Science.gov (United States)

    Fox, Nathan S; Chervenak, Frank A; McCullough, Laurence B

    2008-01-01

    Pregnant patients have the option at delivery of having their cord blood collected and stored for future use. At many hospitals, they have the option of donating their cord blood to the public banking system for future use by anyone who is an appropriate match (public banking). Patients also have the option of having their cord blood stored for a fee with a commercial/private company for future use within their family (private banking). Currently, private banking is not recommended by major obstetric and pediatric professional organizations. We applied current evidence of the risks and benefits of private and public cord blood banking and accepted ethical principles to answer the following two related questions: 1) Do obstetricians have an ethical obligation to comply with a request for private banking? and 2) Do obstetricians have an ethical obligation to routinely offer private banking to women who do not request it? The only situation where there is a known benefit to private banking is when public banking is not available and the patient currently has an affected family member who may benefit from cord blood therapy. We conclude that when presented with a request for private banking, obstetricians have an ethical obligation to explain the lack of proven benefit of this procedure. If the patient still requests private banking, it would be appropriate to comply, because there is minimal or no risk to the procedure. However, obstetricians are not ethically obligated to offer private banking, even when public banking is not available, except in the limited circumstance when the patient currently has an affected family member who may benefit from cord blood therapy.

  16. Vascular smooth muscle progenitor cells: building and repairing blood vessels.

    Science.gov (United States)

    Majesky, Mark W; Dong, Xiu Rong; Regan, Jenna N; Hoglund, Virginia J

    2011-02-04

    Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.

  17. Umbilical cord blood transplantation: the first 25 years and beyond.

    Science.gov (United States)

    Ballen, Karen K; Gluckman, Eliane; Broxmeyer, Hal E

    2013-07-25

    Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.

  18. Isolation of mesenchymal stem cells from equine umbilical cord blood

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low......, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal...

  19. Histamine release from cord blood basophils

    DEFF Research Database (Denmark)

    Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels

    1990-01-01

    The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...

  20. Histamine release from cord blood basophils

    DEFF Research Database (Denmark)

    Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels

    1990-01-01

    The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...

  1. Arrest—Individual Treatment with Cord Blood

    Directory of Open Access Journals (Sweden)

    A. Jensen

    2013-01-01

    Full Text Available Each year, thousands of children incur brain damage that results in lifelong sequelae. Therefore, based on experimental evidence, we explored the therapeutic potential of human cord blood, known to contain stem cells, to examine the functional neuroregeneration in a child with cerebral palsy after cardiac arrest. The boy, whose cord blood was stored at birth, was 2.5 years old and normally developed when global ischemic brain damage occurred resulting in a persistent vegetative state. Nine weeks later, he received autologous cord blood (91.7 mL, cryopreserved, 5.75×10e8 mononuclear cells intravenously. Active rehabilitation (physio- and ergotherapy was provided daily, follow-up at 2, 5, 12, 24, 30, and 40 months. At 2-months follow-up the boy’s motor control improved, spastic paresis was largely reduced, and eyesight was recovered, as did the electroencephalogram. He smiled when played with, was able to sit and to speak simple words. At 40 months, independent eating, walking in gait trainer, crawling, and moving from prone position to free sitting were possible, and there was significantly improved receptive and expressive speech competence (four-word sentences, 200 words. This remarkable functional neuroregeneration is difficult to explain by intense active rehabilitation alone and suggests that autologous cord blood transplantation may be an additional and causative treatment of pediatric cerebral palsy after brain damage.

  2. Pathogens in Maternal Blood and Fetal Cord Blood Using Q-Pcr Assay

    Directory of Open Access Journals (Sweden)

    Guang Qiong Hou

    2006-06-01

    Conclusion: Our results revealed an unexpectedly high incidence of pathogens in fetal cord blood. Screening for the above pathogens in donor cord blood in cord blood banks using Q-PCR is strongly urged to decrease morbidity and mortality rates in fetal cord blood stem cell transplant recipients.

  3. ACOG Committee Opinion No. 648: Umbilical Cord Blood Banking.

    Science.gov (United States)

    2015-12-01

    Once considered a waste product that was discarded with the placenta, umbilical cord blood is now known to contain potentially life-saving hematopoietic stem cells. When used in hematopoietic stem cell transplantation, umbilical cord blood offers several distinct advantages over bone marrow or peripheral stem cells. However, umbilical cord blood collection is not part of routine obstetric care and is not medically indicated. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice for the timing of umbilical cord clamping. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public and private umbilical cord blood banking should be provided. The routine storage of umbilical cord blood as "biologic insurance" against future disease is not recommended.

  4. Committee Opinion No. 648 Summary: Umbilical Cord Blood Banking.

    Science.gov (United States)

    2015-12-01

    Once considered a waste product that was discarded with the placenta, umbilical cord blood is now known to contain potentially life-saving hematopoietic stem cells. When used in hematopoietic stem cell transplantation, umbilical cord blood offers several distinct advantages over bone marrow or peripheral stem cells. However, umbilical cord blood collection is not part of routine obstetric care and is not medically indicated. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice for the timing of umbilical cord clamping. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public and private umbilical cord blood banking should be provided. The routine storage of umbilical cord blood as "biologic insurance" against future disease is not recommended.

  5. Interleukin-3 and granulocyte-macrophage colony-stimulating factor levels of cord blood plasma in term neonates

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ AIM: Umbilical cord blood plasma contain higher hematopoietic stimulatory activities than adult peripheral blood plasma. IL-3 is regarded as multilineage hematopoietic growth factor that acts on primitive pluripotential stem cells and progenitor cells of every lineage except T and B-lymphoid lineage.

  6. Double cord blood transplantation: co-operation or competition?

    Directory of Open Access Journals (Sweden)

    Nikolaos Neokleous

    2011-06-01

    Full Text Available Over the last two decades umbilical cord blood (UCB transplantation (UCBT is increasingly used for a variety of malignant and benign hematological and other diseases. The main factor that limits the use of UCB to low weight recipients, mainly children and adolescents, is its low progenitor cell content. Various alternatives have been exploited to overcome this difficulty, including the transplantation of two UCB units (double umbilical cord blood transplantation, dUCBT. Following dUCBT, donor(s hematopoietic stem cells (HSC can be detected in the peripheral blood of the recipient as soon as 14 days post-transplantation. Sustained engraftment of HSC from one or both donors can be observed- dominance or mixed chimerism respectively, although single donor unit dominance has been observed in over 85% of patients. The underlying biology, which accounts for the interactions both between the two infused UCB units- cooperative or competitive, and with the recipient’s immune system, has not been elucidated.

  7. Hypoxic chondrogenic differentiation of human cord blood stem cells in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael

    Background: Articular chondrocytes and bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the favoured cells for cartilage tissue engineering. Umbilical cord blood has proven an alternative source of MSCs and moreover they may be more potent chondroprogenitor cells than bonemarrow...... MSCs. Purpose / Aim of Study: Multilineage progenitor cells (MLPCs) are clonal cord blood-derived MSCs and may therefore provide a cell source with more reproducible outcomes compared to heterogeneous primary MSC cultures. Materials and Methods: We evaluated the chondrogenic potency of MLPCs...

  8. 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.

  9. Percutaneous ultrasound guided umbilical cord blood sampling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Hyup; Choi, B. I.; Kim, C. W.; Youn, B. H.; Shin, H. C.; Kim, S. O. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    This report describes a technique and the result of percutaneous ultrasound-guided umbilical cord blood sampling and its potential use in the management of diagnostic problems in the second and third trimester of pregnancy. This method has been employed in the prenatal assessment of 19 fetuses at risk for chromosomal disorders, fetal hypoxia and hematologic disorders. This simple and rapid procedure offers a safe access to the fetal circulation

  10. Umbilical cord blood mercury levels in China

    Institute of Scientific and Technical Information of China (English)

    Meiqin Wu,; Chonghuai Yan; Jian Xu; Wei Wu; Hui Li; Xin Zhou

    2013-01-01

    Mercury (Hg) is a well-known neurotoxicant.Hg exposure at high levels can harm individuals of all ages.Even low level exposure to Hg can damage the brain of fetuses and young children,and affect their central nervous system and cognitive development.The aims of our study were to measure total Hg levels in infant umbilical cord blood and to investigate the risk factors associated with total Hg cord blood levels in various cities in China.Our goal was to provide clues for the prevention of Hg exposure in utero.The results indicated that the average cord blood mercury levels (CBMLs) were (1.81 ± 1.93) μg/L,which were lower than those found in most previous studies.The concentrations also differed according to geographic region.The CBMLs were not only associated with family economic and living conditions,but also with diet in pregnant women,especially the intake of marine fish,shellfish,poultry,formula milk and fruits.

  11. Umbilical cord blood transplantation: A review of atricles

    OpenAIRE

    1999-01-01

    Interest in umbilical cord blood as an alternative source of hematopietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that are readily available and rarely contaminated by latent viruses. Moreover, the collection of umbilical cord blood poses no risk to the donor. There is no need for general anesthesia or blood replacement and the procedure causes no discomfort. Current clinical experience suggests that the incidence of GVHD i...

  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. Umbilical cord blood transplantation: A review of atricles

    Directory of Open Access Journals (Sweden)

    Asadi Amoly F

    1999-08-01

    Full Text Available Interest in umbilical cord blood as an alternative source of hematopietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that are readily available and rarely contaminated by latent viruses. Moreover, the collection of umbilical cord blood poses no risk to the donor. There is no need for general anesthesia or blood replacement and the procedure causes no discomfort. Current clinical experience suggests that the incidence of GVHD in umbilical cord blood transplantation is low. These results and associated laboratory findings pose intriguing possibilities for the future of umbilical cord blood stem cells in the setting of unrelated donor transplantation. There are other intriguing possibilities for example cord blood may be an optimal source of pluripotential stem cells for use in genetherapy.

  14. HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China.

    Science.gov (United States)

    Wang, F; He, J; Chen, S; Qin, F; Dai, B; Zhang, W; Zhu, F M; Lv, H J

    2014-02-01

    Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A-B-DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours.

  15. 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.

  16. Cord blood transplantation: can we make it better?

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    Leland eMetheny

    2013-09-01

    Full Text Available Umbilical cord blood is an established source of hematopoietic stem cells for transplantation. It enjoys several advantages over bone marrow or peripheral blood, including increased tolerance for Human Leukocyte Antigen mismatches, decreased incidence of graft-versus-host disease, and easy availability. Unrelated cord blood does have limitations, however, especially in the treatment of adults. In the 24 years since the first umbilical cord blood transplant was performed, significant progress has been made, but delayed hematopoietic engraftment and increased treatment related mortality remain obstacles to widespread use. Here we summarize the latest results of unrelated cord blood transplants, and review strategies under investigation to improve clinical outcomes.

  17. Cord blood transplantation for the treatment of acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Meerim Park; Young-ho Lee

    2013-01-01

    Objective This review discussed the available data on treatment outcomes of cord blood transplantation (CBT) for acute leukemia.Data sources The data cited in this review were obtained from articles listed in Medline and Pubmed.Study selection We reviewed the articles of clinical results from various registries and institutions,as well as our experiences with CBT in children,adolescents and adults.Results This research has clearly shown that cord blood (CB) has several unique characteristics resulting in distinct advantage and disadvantages when compared to transplantation with unrelated donor bone marrow or peripheral blood stem cells.The field of CBT has advanced from investigating its safety and feasibility to addressing more specific issues such as accelerating engraftment,extending access,and examining outcomes in specific subgroups of patients.Many approaches have been investigated in the attempt to improve engraftment and survival.Variable factors have been identified,such as factors related to donor choice (human leukocyte antigen (HLA) compatibility,cell dose,and others) and transplantation (conditioning and graft-versus-host disease prophylaxis regimen).Data support that CB should be considered a reasonable option in those that do not have HLA matched sibling donor and for those in whom the time to transplant is critical.Conclusions CB is a reasonable alternative to unrelated donor bone marrow or peripheral blood progenitor cells for transplantation.Recently developed strategies aimed at improving hematopoietic recovery and reducing early transplantation-related mortality could further improve treatment outcomes of CBT for patients with acute leukemia.

  18. Free erythrocyte porphyrins in cord blood.

    Science.gov (United States)

    Gottuso, M A; Oski, B F; Oski, F A

    1978-05-01

    Red cell free erythrocyte porphyrin determinations were performed on cord blood specimens from 236 term infants and on capillary blood specimens from 63 preterm infants weighing less than 1,500 gm, during the first week of life. These results were contrasted with those obtained from 398 normal infants and children ages 1 to 6 years. The mean FEP value for the infants was significantly higher than that observed in the normal control subjects. In 10.5% of the term infants and 15.9% of the preterm infants, values in excess of 120 microgram/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values were found to have lower serum iron and transferrin saturation values than did infants with low FEP values. These findings suggest that elevations in cord blood FEP values may indicate a state of relative iron deficiency present at birth.

  19. Quality of Red Blood Cells Isolated from Umbilical Cord Blood Stored at Room Temperature

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    Mariia Zhurova

    2012-01-01

    Full Text Available Red blood cells (RBCs from cord blood contain fetal hemoglobin that is predominant in newborns and, therefore, may be more appropriate for neonatal transfusions than currently transfused adult RBCs. Post-collection, cord blood can be stored at room temperature for several days before it is processed for stem cells isolation, with little known about how these conditions affect currently discarded RBCs. The present study examined the effect of the duration cord blood spent at room temperature and other cord blood characteristics on cord RBC quality. RBCs were tested immediately after their isolation from cord blood using a broad panel of quality assays. No significant decrease in cord RBC quality was observed during the first 65 hours of storage at room temperature. The ratio of cord blood to anticoagulant was associated with RBC quality and needs to be optimized in future. This knowledge will assist in future development of cord RBC transfusion product.

  20. Modulation of Chemokine Gene Expression in CD133 Cord Blood-Derived Human Mast Cells by Cyclosporin A and Dexamethasone

    DEFF Research Database (Denmark)

    Holm, Mette; Kvistgaard, Helene; Dahl, Christine

    2006-01-01

    We have recently developed a protocol for generating huge numbers of mature and functional mast cells from in vitro differentiated umbilical cord blood cells. Using CD133 as a positive selection marker to isolate haematopoietic progenitors we routinely expand the number of recovered cells at least...

  1. Cost-effectiveness of private umbilical cord blood banking.

    Science.gov (United States)

    Kaimal, Anjali J; Smith, Catherine C; Laros, Russell K; Caughey, Aaron B; Cheng, Yvonne W

    2009-10-01

    To investigate the cost-effectiveness of private umbilical cord blood banking. A decision-analytic model was designed comparing private umbilical cord blood banking with no umbilical cord blood banking. Baseline assumptions included a cost of $3,620 for umbilical cord blood banking and storage for 20 years, a 0.04% chance of requiring an autologous stem cell transplant, a 0.07% chance of a sibling requiring an allogenic stem cell transplant, and a 50% reduction in risk of graft-versus-host disease if a sibling uses banked umbilical cord blood. Private cord blood banking is not cost-effective because it cost an additional $1,374,246 per life-year gained. In sensitivity analysis, if the cost of umbilical cord blood banking is less than $262 or the likelihood of a child needing a stem cell transplant is greater than 1 in 110, private umbilical cord blood banking becomes cost-effective. Currently, private umbilical cord blood banking is cost-effective only for children with a very high likelihood of needing a stem cell transplant. Patients considering private blood banking should be informed of the remote likelihood that a unit will be used for a child or another family member. III.

  2. The problem of cord blood banking

    Directory of Open Access Journals (Sweden)

    Shved A. D.

    2013-03-01

    Full Text Available The review considers the literature data on issues of cord blood (CB banking in different countries and regions. The existing forms of banks are private, mixed and public, the latter is preferred by most clinicians who are experienced in stem cell transplantation. All the researchers admit the need for development of CB banks, but they note that the progress depends on several factors: the deficit of government financial support and poor people’s awareness of the possibilities of stem cell therapy, the appropriateness and relevance of public resources of CB units in National Banks.

  3. Cord blood banking activity in Iran National Cord Blood Bank: a two years experience.

    Science.gov (United States)

    Jamali, Mostafa; Atarodi, Kamran; Nakhlestani, Mozhdeh; Abolghasemi, Hasan; Sadegh, Hosein; Faranoosh, Mohammad; Golzade, Khadije; Fadai, Razieh; Niknam, Fereshte; Zarif, Mahin Nikougoftar

    2014-02-01

    Today umbilical cord blood (UCB) has known as a commonly used source of hematopoietic stem cells for allogeneic transplantation and many cord blood banks have been established around the world for collection and cryopreservation of cord blood units. Herein, we describe our experience at Iran National Cord Blood Bank (INCBB) during 2 years of activity. From November 2010 to 2012, UCBs were collected from 5 hospitals in Tehran. All the collection, processing, testing, cryopreservation and storage procedures were done according to standard operation procedures. Total nucleated cells (TNC) count, viability test, CD34+ cell count, colony forming unit (CFU) assay, screening tests and HLA typing were done on all banked units. Within 3770 collected units, only 32.9% fulfilled banking criteria. The mean volume of units was 105.2 ml and after volume reduction the mean of TNC, viability, CD34+ cells and CFUs was 10.76×10(8), 95.2%, 2.99×10(6) and 7.1×10(5), respectively. One unit was transplanted at Dec 2012 to a 5-year old patient with five of six HLA compatibilities. In our country banking of UCB is new and high rate of hematopoietic stem cell transplants needs expanding CB banks capacity to find more matching units, optimization of methods and sharing experiences to improve biological characterization of units.

  4. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord.

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    Sharyn L Rossi

    Full Text Available BACKGROUND: Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI. CONCLUSIONS/SIGNIFICANCE: These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.

  5. [Marrow donor registration and cord blood banking: current issues].

    Science.gov (United States)

    Takanashi, Minoko

    2016-03-01

    Marrow donor registration and cord blood banking are essential components of the infrastructure required for unrelated haemopoietic stem cell transplantations. We now have a new law to support and regulate the Marrow Donor Coordination Agency, Cord Blood Banks and the Haematopoietic Stem Cell Provision Support Organization. We also need to have a specific goal for bone marrow and peripheral blood stem cell donor registration, a minimum cord blood bank size, and the demographic data to back the medical needs for unrelated haemopoietic stem cell transplantations. To improve bone marrow and peripheral blood stem cell transplantations, we need to recruit younger adults for marrow registration and make greater efforts to shorten the coordinating period. For cord blood transplantations, uniting and empowering the cord blood collection sites is needed, to encourage and motivate obstetricians and other staff, as the quality of cord blood units is primarily determined during collection. Also, the cord blood banks must work cooperatively to provide cord blood internationally, which includes coordinating with international agencies and their regulations.

  6. Ex vivo expansion of human peripheral blood progenitors.

    Science.gov (United States)

    Chabannon, C; Herrera-Rodriguez, D; Bardin, F; Mouren, M; Novakovitch, G; Blaise, D; Maraninchi, D; Mannoni, P

    1995-01-01

    Culture of human hematopoietic progenitors on a large scale could lead to several clinical applications within the near future, including the production of differentiated and functional cells, the increase in the number of early progenitors, especially stem cells, with such use as gene transfer, or the improvement of grafts used to limit the hematological toxicity associated with high-dose chemotherapy. In this case, one can still distinguish different objectives: improvement of grafts that contain low numbers of progenitors because of prior chemotherapies or because of marrow involvement for example, and qualitative changes in the graft content that would allow to envision the disappearance, or the further reduction, in the duration of absolute neutropenia that follows delivery of high dose chemotherapy ("nadir rescue"), despite substitution of mobilized blood cells to marrow cells and the in vivo use of hematopoietic growth factors. Additional advantages may be related to tumor purging in autologous expanded cells, and to the change in the ratio between hematopoietic progenitors and immunocompetent cells in allogeneic expanded populations. Therefore it appears that in vitro expansion currently raises two types of questions: the first ones are related to the definition of clinical or biological endpoints to be achieved, the second ones are related to "bioengineering", and deal with the efficiency and safety of progenitor cell cultures to be used for clinical applications. We here present preliminary results preparing future pilot clinical studies with ex vivo cultured human hematopoietic cells.

  7. Isolation of mesenchymal stem cells from equine umbilical cord blood

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    Thomsen Preben D

    2007-05-01

    Full Text Available Abstract Background There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low. The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5°C in humidified atmosphere containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were observed. Cellular morphology varied between monolayers of elongated spindle-shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic extensions. Positive Alizarin Red and von Kossa staining as well as significant calcium deposition and alkaline phosphatase activity confirmed osteogenesis. Histology and positive Safranin O staining of matrix glycosaminoglycans illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed adipogenesis. Conclusion We here report, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal model for proof-of-principle studies of cord blood derived MSCs.

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

    Directory of Open Access Journals (Sweden)

    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. Maternal predictors and quality of umbilical cord blood units.

    Science.gov (United States)

    Bielec-Berek, Beata; Jastrzębska-Stojko, Żaneta; Drosdzol-Cop, Agnieszka; Jendyk, Cecylia; Boruczkowski, Dariusz; Ołdak, Tomasz; Nowak-Brzezińska, Agnieszka; Stojko, Rafał

    2017-08-19

    The aim of the study was to determine the relationship between the maternal age at delivery and selected properties of the cord blood stem cells. The study included 50 pregnant women aged between 18 and 38 years in which spontaneous labors or elective cesarean sections were performed. Umbilical cord blood was collected immediately after the women were delivered of newborns. The samples were analyzed in the Polish Stem Cells Bank in Warsaw. The highest mean WBC level (p umbilical blood collected from patients aged 35 years and more. Similarly, the highest mean cell viability was observed in the umbilical cord blood collected from patients aged 35 and more. There were no statistically significant correlations between the CD34+ cells count and mean cell viability in the umbilical cord blood and the maternal age. With the significance level at p umbilical cord blood of patients aged 35 and more after spontaneous labors. In the same group, the umbilical cord blood was also characterized by the highest mean cell viability (98.72%). The number of nucleated cells in the umbilical cord blood collected in the perinatal period increases together with the maternal age. In the course of physiological spontaneous labors, the collected umbilical cord blood has more nucleated cells as compared with elective caesarian sections.

  10. Functional Electrical Stimulation Helps Replenish Progenitor Cells in the Injured Spinal Cord of Adult Rats

    Science.gov (United States)

    Becker, Daniel; Gary, Devin S.; Rosenzweig, Ephron S.; Grill, Warren M.; McDonald, John W.

    2010-01-01

    Functional electrical stimulation (FES) can restore control and offset atrophy to muscles after neurological injury. However, FES has not been considered as a method for enhancing CNS regeneration. This paper demonstrates that FES dramatically enhanced progenitor cell birth in the spinal cord of rats with a chronic spinal cord injury (SCI). A complete SCI at thoracic level 8/9 was performed on 12 rats. Three weeks later, a FES device to stimulate hindlimb movement was implanted into these rats. Twelve identically-injured rats received inactive FES implants. An additional control group of uninjured rats were also examined. Ten days after FES implantation, dividing cells were marked with bromodeoxyuridine (BrdU). The ‘cell birth’ subgroup (half the animals in each group) was sacrificed immediately after completion of BrdU administration, and the ‘cell survival’ subgroup was sacrificed 7 days later. In the injured ‘cell birth’ subgroup, FES induced an 82-86 % increase in cell birth in the lumbar spinal cord. In the injured ‘cell survival’ subgroup, the increased lumbar newborn cell counts persisted. FES doubled the proportion of the newly-born cells which expressed nestin and other markers suggestive of tripotential progenitors. In uninjured rats, FES had no effect on cell birth/survival. This report suggests that controlled electrical activation of the CNS may enhance spontaneous regeneration after neurological injuries. PMID:20059998

  11. Neural progenitor cell apoptosis and differentiation were affected by activated microglia in spinal cord slice culture.

    Science.gov (United States)

    Liu, Xuqing; Chu, Tak-Ho; Su, Huanxing; Guo, Anchen; Wu, Wutian

    2014-03-01

    Neural progenitor cell (NPC) transplantation offers great potential to treat spinal cord injury (SCI). NPCs may replace lost neurons or oligodendrocytes and act as a source of neurotrophic factors to support survival of remaining cells. However, their efficiency was limited by poor survival after transplantation, and they tended more to differentiate into astrocytes, but not neurons and oligodendrocytes. This study investigated whether activated microglia is a factor that contributes to this phenomenon. Organotypic spinal cord slice (SCS) culture was used to mimic the local environment after SCI, and NPCs were co-cultured with them to share the culture medium. After specific depletion of microglia in the SCSs with clodronate loaded liposome, the apoptotic rate of NPCs decreased, more NPCs differentiated into neurons, and glial differentiation was impaired. This suggested that microglia may impair NPC survival, and neuronal differentiation, but improve astrocyte differentiation. In NPC transplantation strategy for SCI, microglia would be manipulated to improve the survival and neuronal differentiation of NPCs.

  12. Response of ependymal progenitors to spinal cord injury or enhanced physical activity in adult rat.

    Science.gov (United States)

    Cizkova, Dasa; Nagyova, Miriam; Slovinska, Lucia; Novotna, Ivana; Radonak, Jozef; Cizek, Milan; Mechirova, Eva; Tomori, Zoltan; Hlucilova, Jana; Motlik, Jan; Sulla, Igor; Vanicky, Ivo

    2009-09-01

    Ependymal cells (EC) in the spinal cord central canal (CC) are believed to be responsible for the postnatal neurogenesis following pathological or stimulatory conditions. In this study, we have analyzed the proliferation of the CC ependymal progenitors in adult rats processed to compression SCI or enhanced physical activity. To label dividing cells, a single daily injection of Bromo-deoxyuridine (BrdU) was administered over a 14-day-survival period. Systematic quantification of BrdU-positive ependymal progenitors was performed by using stereological principles of systematic, random sampling, and optical Dissector software. The number of proliferating BrdU-labeled EC increased gradually with the time of survival after both paradigms, spinal cord injury, or increased physical activity. In the spinal cord injury group, we have found 4.9-fold (4 days), 7.1-fold (7 days), 4.9-fold (10 days), and 5.6-fold (14 days) increase of proliferating EC in the rostro-caudal regions, 4 mm away from the epicenter. In the second group subjected to enhanced physical activity by running wheel, we have observed 2.1-2.6 fold increase of dividing EC in the thoracic spinal cord segments at 4 and 7 days, but no significant progression at 10-14 days. Nestin was rapidly induced in the ependymal cells of the CC by 2-4 days and expression decreased by 7-14 days post-injury. Double immunohistochemistry showed that dividing cells adjacent to CC expressed astrocytic (GFAP, S100beta) or nestin markers at 14 days. These data demonstrate that SCI or enhanced physical activity in adult rats induces an endogenous ependymal cell response leading to increased proliferation and differentiation primarily into macroglia or cells with nestin phenotype.

  13. Time related variations in stem cell harvesting of umbilical cord blood

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Miscio, Giuseppe; Fontana, Andrea; Copetti, Massimiliano; Francavilla, Massimo; Bosi, Alberto; Perfetto, Federico; Valoriani, Alice; De Cata, Angelo; Santodirocco, Michele; Totaro, Angela; Rubino, Rosa; di Mauro, Lazzaro; Tarquini, Roberto

    2016-01-01

    Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units. PMID:26906327

  14. Umbilical cord blood banking: implications for perinatal care providers.

    Science.gov (United States)

    Armson, B Anthony

    2005-03-01

    To evaluate the risks and benefits of umbilical cord blood banking for future stem cell transplantation and to provide guidelines for Canadian perinatal care providers regarding the counselling, procedural, and ethical implications of this potential therapeutic option. Selective or routine collection and storage of umbilical cord blood for future autologous (self) or allogenic (related or unrelated) transplantation of hematopoietic stem cells to treat malignant and nonmalignant disorders in children and adults. Maternal and perinatal morbidity, indications for umbilical cord blood transplantation, short- and long-term risks and benefits of umbilical cord blood transplantation, burden of umbilical cord blood collection on perinatal care providers, parental satisfaction, and health care costs. MEDLINE and PubMed searches were conducted from January 1970 to October 2003 for English-language articles related to umbilical cord blood collection, banking, and transplantation; the Cochrane library was searched; and committee opinions of the Royal College of Obstetricians and Gynaecologists, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists were obtained. The evidence collected was reviewed and evaluated by the Maternal/Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), and recommendations were made using the evaluation of evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam. Umbilical cord blood is a readily available source of hematopoietic stem cells used with increasing frequency as an alternative to bone marrow or peripheral stem cells for transplantation in the treatment of malignant and nonmalignant conditions in children and adults. Umbilical cord blood transplantation provides a rich source of hematopoietic stem cells with several advantages, including prompt availability, decreased risk of transmissible viral infections and graft

  15. Cord blood banking and transplantation: advances and controversies.

    Science.gov (United States)

    Yoder, Mervin C

    2014-04-01

    A review of articles published since January 2012 on the topic of cord blood banking and cord blood stem cell transplantation was conducted for this the 25th anniversary year of the first cord blood transplant performed in a human. Cord blood banking is performed throughout the world. Umbilical cord blood (UCB) transplantation is recognized as an acceptable alternative stem cell source for paediatric and adults requiring a haematopoietic transplant, particularly for patients of racial and ethnic minorities. To further advance the use of UCB, methods to enhance UCB stem cell expansion, engraftment and maintenance may be required. Controversy on the most effective and economically sustainable model for banking and storing an optimal UCB product continues to persist. Cord blood banking and transplantation of cord blood stem cells has advanced rapidly over the initial 25 years, as more than 30 ,000 patients have benefited from the therapy. New concepts on the use of methods to expand UCB stem cells for transplantation and use for nonhaematopoietic indications may increase demand for UCB over the next few decades.

  16. Apheresis techniques for collection of peripheral blood progenitor cells.

    Science.gov (United States)

    Moog, Rainer

    2004-12-01

    The combination of effective mobilisation protocols and efficient use of apheresis machines has caused peripheral blood progenitor cells (PBPC) transplantation to grow rapidly. The development of apheresis technology has improved over the years. Today PBSC procedures have changed towards systems to minimise operator interaction and to reduce the collection of undesired cells such as polymorphonuclear cells and platelets using functionally closed, sterile environments for PBSC collection in keeping with Good Manufacturing Practice guidelines. Blood cell separators with continuous flow technique allow the processing of more blood than intermittent flow devices resulting in higher PBSC yields. Large volume leukapheresis with the processing of 3-4-fold donor's/patient's blood volume can increase the number of collected progenitor cells. Therefore, intermittent flow cell separators are indicated if only single vein access is available. Anticoagulant induced hypocalcaemia is an often observed side effect in long lasting PBPC harvesting and monitoring of electrolytes should be performed especially at the end of the apheresis procedure to supplement low levels of potassium, calcium or magnesium. Refinement and improvement of collection techniques continue to add to the armamentarium of current approaches for cancer and non-malignant conditions and will enable future strategies.

  17. Bilirubin dosage in cord blood: could it predict neonatal hyperbilirubinemia?

    Directory of Open Access Journals (Sweden)

    Adélia Jeha Nasser Bernaldo

    Full Text Available CONTEXT: With early discharge, many newborns have to be readmitted to hospital for hyperbilirubinemia to be treated, and this has been held responsible for the reappearance of kernicterus. OBJECTIVE: To evaluate whether bilirubin levels in cord blood could predict neonatal hyperbilirubinemia that would require treatment, in full-term newborns up to their third day of life. TYPE OF STUDY: Prospective study. SETTING: Neonatal Unit of Hospital Israelita Albert Einstein, São Paulo, Brazil. PARTICIPANTS: 380 full-term newborns considered normal: with or without ABO/Rh blood group incompatibility and without other complications. PROCEDURES: Blood was taken from the umbilical cord for analysis of conjugated, unconjugated and total bilirubin serum levels. The newborns were followed up until discharge, and unconjugated bilirubin that required phototherapy was compared to the cord bilirubin assay. Discriminant analysis was used to classify newborns: with or without risk of needing phototherapy by the third day of life. MAIN MEASUREMENTS: Bilirubin assay in cord blood; mother's and newborn's blood groups; phototherapy indication. RESULTS: The mean value for unconjugated bilirubin in cord blood was significantly higher in newborns whose unconjugated bilirubin required phototherapy. The presence of ABO blood group incompatibility was a significant variable in relation to unconjugated bilirubin that required phototherapy. The most useful cutoff point for unconjugated bilirubin in cord blood was 2.0 mg/100 ml. DISCUSSION: Cord blood could be collected, stored and used for further analysis of unconjugated bilirubin levels as a means for considering whether or not to discharge a moderately jaundiced child from hospital, in association with other resources. CONCLUSIONS: Blood incompatibility between mother and child was a predictor for the appearance of hyperbilirubinemia that required treatment. Considering a cutoff point of 2.0 mg/100 ml, it could be concluded

  18. Hypoxic chondrogenic differentiation of human cord blood stem cells in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael;

    Background: Articular chondrocytes and bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the favoured cells for cartilage tissue engineering. Umbilical cord blood has proven an alternative source of MSCs and moreover they may be more potent chondroprogenitor cells than bonemarrow...... MSCs. Purpose / Aim of Study: Multilineage progenitor cells (MLPCs) are clonal cord blood-derived MSCs and may therefore provide a cell source with more reproducible outcomes compared to heterogeneous primary MSC cultures. Materials and Methods: We evaluated the chondrogenic potency of MLPCs...... in standard micromass pellet system, layered on calcium polyphosphate (CPP), and on semi-permeable polytetrafluoroethane membranes with and without collagen type I, II or IV pre-coating. Findings / Results: The MPLC cell line used in this study possessed poor chondrogenic potency overall, but membrane...

  19. Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking.

    Science.gov (United States)

    Allan, David S; Scrivens, Nicholas; Lawless, Tiffany; Mostert, Karen; Oppenheimer, Lawrence; Walker, Mark; Petraszko, Tanya; Elmoazzen, Heidi

    2016-03-01

    Public banking of umbilical cord blood units (CBUs) containing higher numbers of cells ensures timely engraftment after transplantation for increasing numbers of patients. Delayed clamping of the umbilical cord after birth may benefit some infants by preventing iron deficiency. Implications of delayed cord clamping for public cord blood banking remains unclear. CBUs collected by Canadian Blood Services at one collection site between November 1, 2014, and March 17, 2015, were analyzed. The delay in cord clamping after birth was timed and classified as "no delay," 20 to 60 seconds, more than 60 seconds, or more than 120 seconds. Of 367 collections, 100 reported no delay in clamping while clamping was delayed by 20 to 60 seconds (n = 69), more than 60 seconds (n = 98), or more than 120 seconds (n = 100) in the remaining cases. The mean volume and total nucleated cells (TNCs) in units with no delay in clamping were significantly greater than mean volumes for all categories of delayed clamping (Tukey's test, p clamping was delayed (p = 5.5 × 10(-8) ). The difference was most marked for cords that were clamped more than 120 seconds after delivery (6.2% compared with 39%). Delayed cord clamping greatly diminishes the volume and TNC count of units collected for a public cord blood bank. Creating an inventory of CBUs with high TNC content may take more time than expected. © 2015 AABB.

  20. Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    HU Cheng-heng; LI Zhi-ming; DU Zhi-min; ZHANG Ai-xia; YANG Da-ya; WU Gui-fu

    2009-01-01

    Background Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction.Methods Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-I). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VⅢ immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody,representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization.Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VⅢ staining demonstrated a higher degree of microvessel formation in EPCs transplanted

  1. Cord Blood Banking Standards: Autologous Versus Altruistic.

    Science.gov (United States)

    Armitage, Sue

    2015-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

  2. Toxoplasmosis in cord blood transplantation recipients.

    Science.gov (United States)

    Bautista, G; Ramos, A; Forés, R; Regidor, C; Ruiz, E; de Laiglesia, A; Navarro, B; Bravo, J; Portero, F; Sanjuan, I; Fernández, M N; Cabrera, R

    2012-10-01

    Toxoplasmosis is a devastating opportunistic infection that can affect immunocompromised patients such as cord blood transplantation (CBT) recipients. The clinical characteristics of 4 toxoplasmosis CBT patients treated at our institution are reviewed, together with 5 cases collected from the literature. The rate of toxoplasmosis in our hospital was 6% in CBT recipients and 0.2% in other types of allogeneic hematopoietic stem cell transplantation (P < 0.001). Five patients (56%) presented disseminated toxoplasmosis and 4 patients (44%) had localized infection in the central nervous system. In 5 of the 9 patients considered (56%), cytomegalovirus viral replication had been detected before the clinical onset of toxoplasmosis. Seven patients (78%) had previously developed graft-versus-host disease. All patients who exhibited disseminated disease died due to Toxoplasma infection. Pre-transplant serology was positive in 1 patient, negative in 3 patients, and not performed in another. Only 1 of these 5 patients with disseminated disease had received Toxoplasma prophylaxis with cotrimoxazole. It could be concluded that mortality in CBT patients with disseminated toxoplasmosis is unacceptably high. The negative results of serology in the majority of these cases, and its unspecific clinical presentation, makes diagnosis exceedingly difficult. Better diagnostic tests and prophylaxis strategy are needed in CBT recipients.

  3. Cord blood banking in France: reorganising the national network.

    Science.gov (United States)

    Katz, Gregory; Mills, Antonia

    2010-06-01

    Paradoxically, France is one of the leading exporters of cord blood units worldwide, but ranks only 17th in terms of cord blood units per inhabitant, and imports 64% of cord blood grafts to meet national transplantation demands. With three operational banks in 2008, the French allogeneic cord blood network is now entering an important phase of development with the creation of seven new banks collecting from local clusters of maternities. Although the French network of public banks is demonstrating a strong commitment to reorganise and scale up its activities, the revision of France's bioethics law in 2010 has sparked a debate concerning the legalisation of commercial autologous banking. The paper discusses key elements for a comprehensive national plan that would strengthen the allogeneic banking network through which France could meet its national medical needs and guarantee equal access to healthcare. Copyright 2010. Published by Elsevier Ltd.

  4. Activation and crosstalk between TNF family receptors in umbilical cord blood cells is not responsible for loss of engraftment capacity following culture

    OpenAIRE

    Mizrahi, Keren; Askenasy, Nadir

    2013-01-01

    Umbilical cord blood (UCB) is a rich source of hematopoietic progenitors for transplantation. Murine and human progenitors are insensitive to apoptotic signaling mediated by the TNF family receptors, however extension of culture over 48 hours is accompanied by severe deterioration in engraftment and hematopoietic reconstituting capacity. In this study we assessed crosstalk between the Fas, TNF and TRAIL receptors, and questioned whether it contributes to increased mortality and decreased acti...

  5. Temporal Response of Endogenous Neural Progenitor Cells Following Injury to the Adult Rat Spinal Cord.

    Science.gov (United States)

    Mao, Yilin; Mathews, Kathryn; Gorrie, Catherine A

    2016-01-01

    A pool of endogenous neural progenitor cells (NPCs) found in the ependymal layer and the sub-ependymal area of the spinal cord are reported to upregulate Nestin in response to traumatic spinal cord injury (SCI). These cells could potentially be manipulated within a critical time period offering an innovative approach to the repair of SCI. However, little is known about the temporal response of endogenous NPCs following SCI. This study used a mild contusion injury in rat spinal cord and immunohistochemistry to determine the temporal response of ependymal NPCs following injury and their correlation to astrocyte activation at the lesion edge. The results from the study demonstrated that Nestin staining intensity at the central canal peaked at 24 h post-injury and then gradually declined over time. Reactive astrocytes double labeled by Nestin and glial fibrillary acidic protein (GFAP) were found at the lesion edge and commenced to form the glial scar from 1 week after injury. We conclude that the critical time period for manipulating endogenous NPCs following a spinal cod injury in rats is between 24 h when Nestin expression in ependymal cells is increased and 1 week when astrocytes are activated in large numbers.

  6. Novel, high-yield red blood cell production methods from CD34-positive cells derived from human embryonic stem, yolk sac, fetal liver, cord blood, and peripheral blood.

    Science.gov (United States)

    Olivier, Emmanuel; Qiu, Caihong; Bouhassira, Eric E

    2012-08-01

    The current supply of red blood cells expressing rare blood groups is not sufficient to cover all the existing transfusion needs for chronically transfused patients, such as sickle cell disease homozygous carriers, because of alloimmunization. In vitro production of cultured red blood cells is slowly emerging as a possible complement to the existing collection-based red blood cell procurement system. The yield of cultured red blood cells can theoretically be maximized by amplifying the stem, progenitor, or precursor compartment. Here, we combined methods designed to expand these three compartments to optimize the yield of cultured red blood cells and found that exposing CD34(+) cells to a short pulse of cytokines favorable for erythroid differentiation prior to stem cell expansion followed by progenitor expansion produced the highest yield of erythroid cells. This novel serum-free red blood cell production protocol was efficient on CD34(+) cells derived from human embryonic stem cells, 6-8-week yolk sacs, 16-18-week fetal livers, cord blood, and peripheral blood. The yields of cells obtained with these new protocols were larger by an order of magnitude than the yields observed previously. Globin expression analysis by high-performance liquid chromatography revealed that these expansion protocols generally yielded red blood cells that expressed a globin profile similar to that expected for the developmental age of the CD34(+) cells.

  7. Saving the leftovers: models for banking cord blood stem cells.

    Science.gov (United States)

    Cogdell, Kimberly J

    2009-01-01

    Each year there are over four million live births in the United States. Each birth produces umbilical cord blood stem cells, which are usually discarded. The author argues that rather than discarding the umbilical cord, this valuable resource of cord blood should be banked and used for research and therapeutic purposes. Umbilical cord blood could provide a solution to the critical need to find matching donors for hematopoietic transplants in patients who have no matching bone marrow donors. Creating a system of universal donation to a public bank will greatlyincrease the number of donors and therefore, the number of matches for patients. Such a system will facilitate the development and use of new technologies and transplant procedures, while providing an opportunity for treatment to individuals who would otherwise not be able to find suitable donors.

  8. Effect of delayed umbilical cord clamping on blood gas analysis.

    Science.gov (United States)

    Valero, Javier; Desantes, Domingo; Perales-Puchalt, Alfredo; Rubio, Juan; Diago Almela, Vicente J; Perales, Alfredo

    2012-05-01

    To ascertain if there are differences in umbilical cord blood gas analysis between immediate and delayed cord clamping. In a prospective observational study on 60 vaginally delivered healthy term newborns, we sampled umbilical cord blood immediately after delivery and at the time umbilical cord pulsation spontaneously ceased. There were significant decreases in pH, oxygen saturation (sO(2)), glycemia, oxygen content (ctO(2)), bicarbonate (HCO(3)(-)) and base excess (BE). Lactate and [Formula: see text] increased. Delayed cord clamping pH correlated with immediate cord clamping pH, [Formula: see text] , ctHb, sO(2) and time (r(2)=0.77, pcord clamping lactate was associated with immediate cord clamping lactate and time (r(2)=0.83, pcord clamping alters acid-base parameters and lactate values compared to immediate cord clamping. Those variations depend mainly on time, prior pH and lactate. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Connexin 50 Expression in Ependymal Stem Progenitor Cells after Spinal Cord Injury Activation.

    Science.gov (United States)

    Rodriguez-Jimenez, Francisco Javier; Alastrue-Agudo, Ana; Stojkovic, Miodrag; Erceg, Slaven; Moreno-Manzano, Victoria

    2015-11-06

    Ion channels included in the family of Connexins (Cx) help to control cell proliferation and differentiation of neuronal progenitors. Here we explored the role of Connexin 50 (Cx50) in cell fate modulation of adult spinal cord derived neural precursors located in the ependymal canal (epSPC). epSPC from non-injured animals showed high expression levels of Cx50 compared to epSPC from animals with spinal cord injury (SCI) (epSPCi). When epSPC or epSPCi were induced to spontaneously differentiate in vitro we found that Cx50 favors glial cell fate, since higher expression levels, endogenous or by over-expression of Cx50, augmented the expression of the astrocyte marker GFAP and impaired the neuronal marker Tuj1. Cx50 was found in both the cytoplasm and nucleus of glial cells, astrocytes and oligodendrocyte-derived cells. Similar expression patterns were found in primary cultures of mature astrocytes. In addition, opposite expression profile for nuclear Cx50 was observed when epSPC and activated epSPCi were conducted to differentiate into mature oligodendrocytes, suggesting a different role for this ion channel in spinal cord beyond cell-to-cell communication. In vivo detection of Cx50 by immunohistochemistry showed a defined location in gray matter in non-injured tissues and at the epicenter of the injury after SCI. epSPCi transplantation, which accelerates locomotion regeneration by a neuroprotective effect after acute SCI is associated with a lower signal of Cx50 within the injured area, suggesting a minor or detrimental contribution of this ion channel in spinal cord regeneration by activated epSPCi.

  10. Connexin 50 Expression in Ependymal Stem Progenitor Cells after Spinal Cord Injury Activation

    Directory of Open Access Journals (Sweden)

    Francisco Javier Rodriguez-Jimenez

    2015-11-01

    Full Text Available Ion channels included in the family of Connexins (Cx help to control cell proliferation and differentiation of neuronal progenitors. Here we explored the role of Connexin 50 (Cx50 in cell fate modulation of adult spinal cord derived neural precursors located in the ependymal canal (epSPC. epSPC from non-injured animals showed high expression levels of Cx50 compared to epSPC from animals with spinal cord injury (SCI (epSPCi. When epSPC or epSPCi were induced to spontaneously differentiate in vitro we found that Cx50 favors glial cell fate, since higher expression levels, endogenous or by over-expression of Cx50, augmented the expression of the astrocyte marker GFAP and impaired the neuronal marker Tuj1. Cx50 was found in both the cytoplasm and nucleus of glial cells, astrocytes and oligodendrocyte-derived cells. Similar expression patterns were found in primary cultures of mature astrocytes. In addition, opposite expression profile for nuclear Cx50 was observed when epSPC and activated epSPCi were conducted to differentiate into mature oligodendrocytes, suggesting a different role for this ion channel in spinal cord beyond cell-to-cell communication. In vivo detection of Cx50 by immunohistochemistry showed a defined location in gray matter in non-injured tissues and at the epicenter of the injury after SCI. epSPCi transplantation, which accelerates locomotion regeneration by a neuroprotective effect after acute SCI is associated with a lower signal of Cx50 within the injured area, suggesting a minor or detrimental contribution of this ion channel in spinal cord regeneration by activated epSPCi.

  11. [Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

    Science.gov (United States)

    Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

    2013-08-01

    Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

  12. 人巨细胞病毒感染致造血祖细胞增殖抑制与更昔洛韦的影响%Inhibitory effect of ganciclovir on proliferation of cord blood hematopoietic progenitor cells after infection of human cytomegalovirus in vitro

    Institute of Scientific and Technical Information of China (English)

    刘文君; 刘斌; 郭渠莲; 付晓冬; 邓正华

    2008-01-01

    BACKGROUND: Clinically, in patients undergoing hematopoietic stem cell transplantation (HSCT), human cytomegalovirus (HCMV) can be associated with delayed platelet engraftment, phenotypically abnormal peripheral blood leukocytes, and graft rejection, possibly through a direct viral effect on hematopoietic progenitor cells after HCMV infection. OBJECTIVE: To investigate the inhibitory effect of ganciclovir (GCV) on proliferation of colony forming unit (CFU) granulocyte-macrophage (CFU-GM), CFU-erythroid (CFU-E), CFU T-lymphocyte (CFU-TL), CFU-multipotential (CFU-Mix) and CFU-megakaryocyte (CFU-Mk) progenitor cells of cord blood (CB) and the protective effects on them. DESIGN: Contrast observational study.SETTING: Department of Molecular Biology, Affiliated Hospital of Luzhou Medical College.PARTICIPANTS: A total of 20 cord blood (CB) samples (with 10 mL for each sample) from fetal umbilical vein of normal term spontaneous delivery neonates were provided by the Department of Gynaecology and Obstetrics, Affiliated Hospital of Luzhou Medical College. All the patients were informed and agreed with the experiment.METHODS: The experiment was carried out in the Department of Molecular Biology, Affiliated Hospital of Luzhou Medical College from June 2004 to December 2006. Colony forming unit-assay was applied to observe the suppression effect of HCMV-AD169 strain on CFU-GM, CFU-E, CFU-TL, CFU-Mix and CFU-Mk of CB with the presence of GCV. The techniques of polymerase chain reaction (PCR) and fluorescence quantification PCR were used to demonstrate the existence of HCMV-AD169 DNA in the colony cells of cultured CFU-GM, CFU-E, CFU-TL, CFU-Mix and CFU-Mk. Normal progenitor cells culture system was regarded as blank control group; normal progenitor cells culture system with inactivated HCMV fluid as inactivated (IV) control group.MAIN OUTCOME MEASURES: ① The number and maintaining duration of colonies of cultured progenitor cells were counted by using a light inverted phase

  13. Different strategies to improve the use of the umbilical cord and cord blood for hematopoietic and other regenerative cell therapies

    NARCIS (Netherlands)

    Garde, Mark Paul van der

    2016-01-01

    The umbilical cord and cord blood contain stem cells that can be used for regenerative cell therapies such as hematopoietic stem cell transplantation. However, the application of cord blood is hindered by the slow engraftment of the cells and delayed immune reconstitution compared to stem cells of

  14. Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

    Directory of Open Access Journals (Sweden)

    David Zvara

    2004-01-01

    Full Text Available Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8, and control (CTRL, n = 8. Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7, ischemic preconditioning (IPC, n = 7, and time control (TC, n = 4. Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

  15. Could cord blood cell therapy reduce preterm brain injury?

    Science.gov (United States)

    Li, Jingang; McDonald, Courtney A; Fahey, Michael C; Jenkin, Graham; Miller, Suzanne L

    2014-01-01

    Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications.

  16. Could cord blood cell therapy reduce preterm brain injury?

    Directory of Open Access Journals (Sweden)

    Jingang eLi

    2014-10-01

    Full Text Available Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP. Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB derived from preterm and term infants for use in clinical applications.

  17. Cord blood unit bankability can be predicted by prenatal sonographic parameters.

    Science.gov (United States)

    Cobellis, L; Castaldi, M A; Trabucco, E; Imparato, G; Perricone, F; Frega, V; Signoriello, G; Colacurci, N

    2013-10-01

    To identify possible sonographic prenatal parameters and postnatal parameters in order to obtain more bankable cord blood units (CBUs) containing a high number of primitive progenitor cells, allowing CBUs to be used as a source of haematopoietic progenitors for clinical transplantation. Prospective study undertaken in the Department of Gynaecology, Obstetrics and Reproductive Science, Second University of Naples, Italy. In total, 219 unrelated CBU donors were enrolled. Ultrasound parameters (biparietal diameter, head circumference, abdominal circumference, femur length, estimation of fetal weight, umbilical artery pulsatility index), collected at hospital admission, together with birth weight and placental weight, were correlated with bankable CBU parameters (CBU volume, total nucleated cell count, CD34+ cell count). Femur length and abdominal circumference correlated positively with bankable CBUs. Receiver operating curve analysis showed that these parameters can identify bankable CBUs. This is the first prospective study to show the relationship between ultrasonographic fetal parameters at term and the possibility of obtaining high-quality CBUs. As such, cord blood banking could be improved worldwide by performing low-cost ultrasonographic scans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Evaluation of the expansion of umbilical cord blood derived from CD133+ cells on biocompatible microwells

    Directory of Open Access Journals (Sweden)

    Mina Soufizomorrod

    2016-05-01

    Full Text Available Background: Hematopoietic stem cell transplantation (HSCT is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB has known as an alternative for hematopoietic stem/progenitor cells (HPSC in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB. Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells’ proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.

  19. Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner.

    Directory of Open Access Journals (Sweden)

    Cynthia Garcia

    Full Text Available OBJECTIVE: Individuals with the neurofibromatosis type 2 (NF2 cancer predisposition syndrome develop spinal cord glial tumors (ependymomas that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC neural progenitor cells (NPCs. METHODS: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. RESULTS: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. SIGNIFICANCE: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma.

  20. Neuron-specific enolase: reference values in cord blood.

    Science.gov (United States)

    Kintzel, K; Sonntag, J; Strauss, E; Obladen, M

    1998-04-01

    With foetal sonography prenatal detection of tumours has become more frequent. To evaluate and treat these infants it is necessary to identify the tumour postnatally. Elevated neuron-specific enolase is a biochemical marker of neuroblastoma. Since conditions during birth may influence neuron-specific enolase concentration in foetal serum, specific reference values in cord blood are required. Cord blood samples were taken from 192 healthy term newborns and concentration of neuron-specific enolase was measured by enzyme immunoassay (EIA). Median neuron-specific enolase concentration in the reference group was 8.0 micrograms/l and the 5th-95th percentiles were 4.8-19.4 micrograms/l. No differences between male and female newborns were detected (p = 0.13). Measurement of neuron-specific enolase in cord blood, in comparison with our reference values, offers an early postnatal possibility of confirming the diagnosis of neuroblastoma.

  1. Sangue de cordão umbilical para uso autólogo ou grupo de pacientes especiais The potential therapeutic use of cord blood in autologous transplants or in special patients: a review and update

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Cruz

    2009-05-01

    Full Text Available O sangue de cordão umbilical e placentário (SCUP é uma rica fonte de células-tronco (CT hematopoéticas e é amplamente utilizado como substituto da medula óssea em casos de transplante. As células do SCUP possuem vantagens sobre as células da medula óssea (MO, principalmente por serem mais jovens e apresentarem maior taxa proliferativa. Além dos progenitores hematopoéticos, o sangue de cordão umbilical contém progenitores endoteliais e mesenquimais, sugerindo sua possível aplicação nos novos protocolos de terapia celular para diferentes tecidos. Na presente revisão, discutimos a importância do armazenamento do sangue de cordão umbilical autólogo e as pesquisas desenvolvidas para a sua aplicação em doenças degenerativas.Umbilical Cord Blood is a rich source of hematopoietic stem cells widely used as a substitute of bone marrow (BM in transplants. Cells from umbilical cord blood present advantages over BM cells, mainly as they are younger and a have higher proliferative rate. Besides hematopoietic stem cells, umbilical cord blood contains endothelial and mesenchymal progenitor cells, suggesting their possible application in cell therapy protocols for different tissues. In this paper, we discuss the importance of autologous umbilical cord blood storage and the research on stem cell transplantation for degenerative diseases.

  2. File list: ALL.Bld.05.AllAg.Umbilical_cord_blood [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Bld.50.AllAg.Umbilical_cord_blood [Chip-atlas[Archive

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  1. File list: Unc.Bld.50.AllAg.Umbilical_cord_blood [Chip-atlas[Archive

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  5. Endothelial Progenitor Cells in Peripheral Blood of Cardiac Catheterization Personnel

    Directory of Open Access Journals (Sweden)

    Soheir Korraa1, Tawfik M.S.1, Mohamed Maher 2 and Amr Zaher

    2014-07-01

    Full Text Available Background: The aim of the present study was to evaluate the rejuvenation capacity among cardiac catheterization technicians occupationally exposed to ionizing radiation. Subjects and methods: The individual annual collective dose information was measured by thermoluminscent personal dosimeters (TLD for those technicians and found to be ranging between 2.16 and 8.44 mSv/y. Venous blood samples were obtained from 30 cardiac catheterization technicians exposed to X-ray during fluoroscopy procedures at the National Heart Institute in Embaba. The control group involved 25 persons not exposed to ionizing radiation and not working in hospitals in addition to 20 persons not exposed to ionizing radiation and working in hospitals. Blood samples were assayed for total and differential blood counts, micronucleus formation (FMN plasma stromal derived growth factor-1α (SDF-1 α and cell phenotype of circulating endothelial progenitor cells (EPCs, whose surface markers were identified as the CD34, CD133 and kinase domain receptors (KDR. Results: SDF-1α (2650± 270 vs. 2170 ± 430 pg/ml and FMN (19.9 ± 5.5 vs. 2.8 ± 1.4/1000 cells were significantly higher among cardiac catheterization staff compared to those of the controls respectively. Similarly, EPCs: CD34 (53 ± 3.9 vs. 48 ± 8.5/105 mononuclear cells, CD133 (62.4 ± 4.8 vs. 54.2 ± 10.6 /105 mononuclear cells KDR (52.7 ± 10.6 vs.43.5± 8.2 /105 mononuclear cells were also significantly higher among cardiac catheterization staff compared to the values of controls respectively. Smoking seemed to have a positive effect on the FMN and SDF-1 but had a negative effect on EPCs. It was found that among cardiac catheterization staff, the numbers of circulating progenitor cells had increased and accordingly there was an increased capacity for tissue repair. Conclusion: In conclusion, the present work shows that occupational exposure to radiation, well within permissible levels, leaves a genetic mark on the

  6. Umbilical Cord Blood Lead Levels and Neonatal Behaviour

    Directory of Open Access Journals (Sweden)

    M. L. de Cáceres

    1995-01-01

    Full Text Available Negative correlations have been found between cord blood lead levels and scores on the Brazelton Neonatal Behaviour Assessment in 30 otherwise healthy newborns. Items in the Habituation, Orientation and Regulation of state clusters, particularly those items related to self-regulatory, self-quieting and auditory habituation, showed lower scores (worse performance in those newborns with higher cord blood lead levels. These disturbances are potentially important since this type of behavior may interfere with the normal process of adaptation to their environment, leading to a less than optimal bonding between newborns and their carers.

  7. 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.

  8. Effects of delayed umbilical cord clamping on peripheral blood hematopoietic stem cells in premature neonates.

    Science.gov (United States)

    Gokmen, Zeynel; Ozkiraz, Servet; Tarcan, Aylin; Kozanoglu, Ilknur; Ozcimen, Emel Ebru; Ozbek, Namik

    2011-05-01

    To investigate the effects of delayed cord clamping (DCC) on peripheral hematopoietic progenitor cells (HPCs) and hematological parameters in premature infants (cord clamping (ICC) at 5-10 s and 21 infants to DCC at 30-45 s. One milliliter blood sample was taken in the first 30 min of life. HPCs were measured by three-color flow cytometry using monoclonal antibodies. There were no significant differences between groups in either maternal or neonatal demographics. All HPC counts were higher in the ICC group, but the difference was not significant. CD34+ cell counts were 45.3 ± 36.6/μL in the ICC and 33.2 ± 26.6/μL in the DCC group (P=0.33); multi-potent progenitor cell counts were 43.2 ± 35/μL in the ICC and 31.1 ± 26.6/μL in the DCC group (P=0.28); and hematopoietic stem cell counts were 2.1 ± 2.1/μL in the ICC and 2.1 ± 3.1/μL in the DCC group (P=0.66). Contrary to our expectation, all HPC counts were lower in the DCC group.

  9. Good practices in collecting umbilical cord and placental blood

    Directory of Open Access Journals (Sweden)

    Lauren Auer Lopes

    Full Text Available Abstract Objective: to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. Method: this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1 verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2 definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r and R(r. Results: while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. Conclusion: the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality.

  10. Pharmacokinetic studies on fenoterol in maternal and cord blood.

    Science.gov (United States)

    von Mandach, U; Huch, A; Huch, R

    1989-04-01

    Fenoterol plasma concentrations were measured by radioimmunoassay in 38 pregnant women at different stages of preterm labor and in cord blood. Eight women were treated intravenously until delivery with 1.0 to 4 micrograms/min of fenoterol for periods ranging from 27 hours to 27 days; blood samples were taken at the same time as cord blood. In these women the fenoterol concentrations in cord blood ranged from 18 to 53% of the maternal concentrations. In eight women treated intravenously with 1.2 to 4.0 micrograms/min for 2 to 15 days, the infusion was stopped 1.3 to 38 hours before delivery. In these instances the concentrations in cord blood reached as much as 90% of the maternal, meaning that the rate of elimination from fetal plasma is lower than that from maternal plasma. Five women were treated daily with 20 to 30 mg per os for 3 to 17 days (three of these women had also had intravenous treatment before). The ratio of cord to maternal blood concentrations was higher than in women receiving the drug intravenously, the relative times of sampling being the same. The findings suggest that: (1) the placental transfer of fenoterol is higher than that found in previous studies in humans and animals with tritium-labeled substances; (2) the rate of fenoterol elimination from fetal plasma after intravenous and oral long-term therapy is lower than that from maternal plasma; (3) after oral administration, the ratios of fetal to maternal fenoterol concentrations are higher than after intravenous infusion.

  11. 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.

  12. SCREENING CORD BLOOD FOR HEMOGLOBINOPATHIES AND THALASSEMIA BY HPLC

    NARCIS (Netherlands)

    VANDERDIJS, FPL; VANDENBERG, GA; SCHERMER, JG; MUSKIET, FD; LANDMAN, H; MUSKIET, FAJ

    1992-01-01

    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns we

  13. Cord blood transplants for SCID: better B-cell engraftment?

    Science.gov (United States)

    Chan, Wan-Yin; Roberts, Robert Lloyd; Moore, Theodore B; Stiehm, E Richard

    2013-01-01

    Hematopoietic stem-cell transplantation is the treatment of choice for severe combined immunodeficiency (SCID). Despite successful T-cell engraftment in transplanted patients, B-cell function is not always achieved; up to 58% of patients require immunoglobulin therapy after receiving haploidentical transplants. We report 2 half-sibling males with X-linked γ-chain SCID treated with different sources of stem cells. Sibling 1 was transplanted with T-cell-depleted haploidentical maternal bone marrow and sibling 2 was transplanted with 7/8 human leukocyte antigen-matched unrelated umbilical cord blood. Both patients received pretransplant conditioning and posttransplant graft-versus-host-disease prophylaxis. B-cell engraftment and function was achieved in sibling 1 but not in sibling 2. This disparate result is consistent with a review of 19 other SCID children who received cord blood transplants. B-cell function, as indicated by no need for immunoglobulin therapy, was restored in 42% of patients given haploidentical transplants and in 68% of patients given matched unrelated donor transplants compared with 80% of patients given cord blood transplants. Cord blood is an alternative source of stem cells for transplantation in children with SCID and has a higher likelihood of B-cell reconstitution.

  14. SCREENING CORD BLOOD FOR HEMOGLOBINOPATHIES AND THALASSEMIA BY HPLC

    NARCIS (Netherlands)

    VANDERDIJS, FPL; VANDENBERG, GA; SCHERMER, JG; MUSKIET, FD; LANDMAN, H; MUSKIET, FAJ

    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns

  15. 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.

  16. Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

    Science.gov (United States)

    Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

    2017-07-01

    Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Is there any reason to prefer cord blood instead of adult donors for hematopoietic stem cell transplants?

    Directory of Open Access Journals (Sweden)

    Meral eBeksac

    2016-01-01

    Full Text Available As cord blood (CB enables rapid access and tolerance to HLA mismatches, number of unrelated cord blood transplants have reached 30 000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified CBUs reaching more than 600 000 CBUs stored worldwide. Efforts to increase stem cell content or engraftment rate of the graft by ex vivo expansion, modulation by molecules such as fucose, Prostaglandin E2 derivative, complement, CD26 inhibitors or CXCR4/CXCL12 axis have been able to accelerate engraftment speed and rate. Furthermore introduction of reduced intensity conditioning protocols, better HLA matching and recognition of the importance of HLA-C have improved CBT success by decreasing Transplant Related Mortality (TRM. Cord blood progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to BM-MSC and less oncogenic potential than Induced Progenitor Stem Cells. This chapter summarizes the advantage and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

  18. The in Vitro Assessment of Biochemical Factors in Hepatocyte like Cells Derived from Umbilical Cord Blood Stem Cells

    Directory of Open Access Journals (Sweden)

    A KHoramroodi

    2009-10-01

    Full Text Available Introduction & Objective: Umbilical cord blood (UCB is a source of Hematopoietic Stem Cells (HSC and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders. Mesenchymal stem cell-derived from umbilical cord blood (UCB have been differentiated to some kind of cells, such as osteobblast, adipoblast and chondroblast in Vitro. This study examined the differentiation of Umbilical Cord Blood (UCB derived stem cells to functional hepatocytes. Materials & Methods: The present study was an experimental study which was carried out in the Payam-e-Noor University of Tehran in cooperation with Hamedan University of Medical Sciences in 2008. Umbilical cord blood (UCB was obtained from Fatemieh hospital (Hamadan, Iran. Stem cells were isolated from the cord blood by combining density gradient centrifugation with plastic adherence. When the isolated cells reached 80% confluence, they differentiated to hepatocyte like cells. The medium which was used was consists of DMEM and 10% Fetal Bovine Serum (FBS supplemented with 20 ng/mL Hepatocyte Growth Factor (HGF, 10 ng/mL basic Fibroblast Growth Factor (bFGF and 20 ng/mL Oncostatin M (OSM.The medium was changed every 3 days and stored for Albumin (ALB, Alpha Fetoprotein (AFP, Alkaline Phosphatase (ALP, and urea assay. Finally PAS stain was done to study Glycogen storage in the differentiated cell. Results: Measurement of biochemical factors in different days showed that concentration of albumin (ALB, alpha fetoprotein (AFP, alkaline phosphatase (ALP, and Urea gradually increased. Also, PAS staining showed the storage of glycogen in these cells. Conclusion: Stem cell-derived from human umbilical cord blood (HUCB is a new source of cell types for cell transplantation therapy of hepatic diseases and under certain conditions these cells can differentiate into liver cells.

  19. Umbilical Cord Blood: Counselling, Collection, and Banking.

    Science.gov (United States)

    Armson, B Anthony; Allan, David S; Casper, Robert F

    2015-09-01

    Objectif : Analyser les données probantes actuelles sur le counseling, le prélèvement et la mise en banque, en ce qui a trait au sang de cordon ombilical, et fournir des lignes directrices aux professionnels canadiens de la santé en ce qui concerne la sensibilisation des patientes, le consentement éclairé, les aspects techniques et les options pour la mise en banque de sang de cordon au Canada. Options : Prélèvement sélectif ou systématique et mise en banque du sang de cordon ombilical, en vue de futures greffes autologues (chez le patient même) ou allogéniques (lien de parenté ou non) de cellules souches visant la prise en charge de troubles malins et bénins chez les enfants et les adultes. Le sang de cordon peut être prélevé au moyen de techniques in utero ou ex utero. Issues : Counseling, prélèvement et mise en banque en ce qui a trait au sang de cordon ombilical, formation des professionnels de la santé, indications du prélèvement de sang de cordon, risques et avantages à court et à long terme, morbidité maternelle et périnatale, satisfaction parentale et coûts de santé. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline et PubMed à partir de septembre 2013, au moyen d’un vocabulaire contrôlé (p. ex. « fetal blood », « pregnancy », « transplantation », « ethics ») et de mots clés (p. ex. « umbilical cord blood », « banking », « collection », « pregnancy », « transplantation », « ethics », « public », « private ») MeSH appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs. Aucune limite n’a été imposée en matière de date, mais les résultats ont été limités aux articles publiés en anglais ou en français. Les recherches ont été mises à jour de façon régulière et int

  20. Private Cord Blood Banking: Experiences And Views Of Pediatric Hematopoietic Cell Transplantation Physicians

    Science.gov (United States)

    Thornley, Ian; Eapen, Mary; Sung, Lillian; Lee, Stephanie J.; Davies, Stella M.; Joffe, Steven

    2011-01-01

    Objective Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation (HCT) physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. Participants and Methods Emailed cross-sectional survey of pediatric HCT physicians in the United States and Canada. 93/152 potentially eligible physicians (93/130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. Results Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36/40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alternative stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with one healthy sibling when both parents were of Northern European descent; 11% would recommend banking when parents were of different minority ethnicities. Conclusions Few transplants have been performed using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric HCT physicians endorse private cord blood banking in the absence of an identified recipient

  1. Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission: a comparison with allografts from adult unrelated donors

    Science.gov (United States)

    Marks, David I.; Woo, Kwang Ahn; Zhong, Xiaobo; Appelbaum, Frederick R.; Bachanova, Veronika; Barker, Juliet N.; Brunstein, Claudio G.; Gibson, John; Kebriaei, Partow; Lazarus, Hillard M.; Olsson, Richard; Perales, Miguel-Angel; Pidala, Joseph; Savani, Bipin; Rocha, Vanderson; Eapen, Mary

    2014-01-01

    Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and –DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2–4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor. PMID:24056817

  2. 脐血单个核细胞来源红系祖细胞的诱导扩增及保存的研究%The induction and cryopreservation of erythroid progenitor cells derived from umbilical cord blood mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    陈琳; 范增; 裴雪涛; 谢小燕; 习佳飞; 吕洋; 田宇; 刘大庆岳文; 李艳华; 南雪; 李思婷

    2016-01-01

    Objective To discover the techniques for ex vivo generation and cryopreservation of erythroid progenitor cells(EPCs)derived from umbilical cord blood(UCB)mononuclear cells(MNCs). Methods UCB was chosen as the source of EPCs. Erythrocytes were precipitated by hydroxyethyl starch (HES). MNCs were separated by Ficoll density gradient centrifugation. Erythroid progenitor cell were generated from MNC ex vivo in suspension culture supplemented with stem cell growth factor, insulin growth factor, erythropoietin, Fms- liketyrosinekinase ligand, transferrin and dexamethasone. Cell maturation was evaluated by morphologic analysis and CD71/CD235a expression profiling. In vitro induced cells were cryopreserved using different cryopreservation media. The cell survival rate, phenotype and proliferation curves were detected after cell thawing. Results With the extension of culture time, the total number of cells increased significantly accompanied with the elevation of CD71 and CD235 positive populations. After 14-day inducing, the cells reached to approximately 110 times of the starting number with the cell viability as(88.92±0.95)%. The percentages of cell surface markers were(86.77±9.11)%forCD71 and(64.47 ± 16.67)% for CD71/CD235, respectively. With the extension of inducing time, wright-Giemsa staining showed that the middle erythroblasts appeared mostly at day 10, and the late erythroblasts were seen at day 14. The red pellets were present at day 14, which indicated the more production of hemoglobin. Colony forming assay showed that erythroid colonies at induction day 7 were higher than that for non-induced cells(326.00 ± 97.96 vs 61.60 ± 20.03 per 2 000 cells). With the extension of culture time, the number of erythroid colonies decreased. Induced EPCs were preserved with different cryopreservation solutions, in which 10%DMSO were better than 5%DMSO. Additionally, 10%DMSO+2%HSA showed no different with 10% DMSO + 5% HSA. Combined 50% plasma with 2% HSA was more

  3. Transplante de sangue de cordão umbilical - SCU Umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Celso A. Rodrigues

    2010-05-01

    Full Text Available A frequente utilização de sangue de cordão umbilical - SCU como fonte de células- tronco hematopoéticas - CTH, tanto em crianças, como em adultos, que não dispõem de doador na família, tem levado ao estabelecimento da padronização de critérios em sua seleção, objetivando a obtenção de melhores resultados. A escolha da unidade de SCU deve basear-se no número total de células nucleadas e no número de diferenças de antígenos leucocitários humanos (HLA. Diante de uma unidade com celularidade mínima, deve-se considerar a possibilidade da utilização de duplo cordão. Frente a mais de uma unidade com características semelhantes, a realização da contagem de células CD34 e da compatibilidade ABO, assim como a qualidade e a rapidez para obtenção da unidade, podem definir a escolha.The frequent use of umbilical cord blood as the source of hematopoietic stem cells, both in children and adults who do not have related donors, has led to the establishment of a better standardization of selection criteria aiming at improving the results. The choice of the umbilical cord blood unit should be based on the total number of nucleated cells and the number of differences in the human leukocyte antigen (HLA system. When a unit has minimal cellularity, the use of a double cord blood transplant should be considered. When two or more units have similar characteristics, the choice may be determined by the CD34 count, ABO compatibility and the quality and speed to obtain the unit.

  4. Comparison of Umbilical Cord Milking and Delayed Cord Clamping on Cerebral Blood Flow in Term Neonates.

    Science.gov (United States)

    Jaiswal, Prateek; Upadhyay, Amit; Gothwal, Sunil; Chaudhary, Hema; Tandon, Ashutosh

    2015-10-01

    To compare the effect of umbilical cord milking (UCM) and delayed cord clamping (DCC) on cerebral blood flow in term neonates. This randomized controlled trial was conducted at a teaching hospital in India during 2012 to 2013. Two hundred newborns (>36wk) were randomized to UCM and DCC groups. UCM was done on 25cm of cord length. In DCC group, clamping was delayed by 60 to 90s. Resistive Index (RI), Pulsatility Index (PI) and cerebral blood flow velocities of middle cerebral artery (MCA) were measured at 24 to 48h of life. Baseline characteristics and hemodynamic parameters were comparable. Mean PI [1.18 (0.26)] and RI [0.65 (0.08)] in UCM group was comparable to mean PI [1.18 (0.25)] and RI [0.65 (0.08)] in DCC group. The peak systolic velocity and end diastolic velocity (cm/s) of blood flow in MCA for UCM group were 34.94 (11.82) and 11.71 (4.75) respectively, while in DCC group they were 37.24 (12.63) and 13.07 (4.78) (p 0.23 and 0.07) respectively. Indices among growth retarded babies were not different. DCC and UCM had similar effect on cerebral blood flow velocities and Doppler indices in MCA, in term neonates.

  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. Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry.

    Science.gov (United States)

    Demange, Elise; Kassim, Yusra; Petit, Cyrille; Buquet, Catherine; Dulong, Virginie; Cerf, Didier Le; Buchonnet, Gérard; Vannier, Jean-Pierre

    2013-11-01

    Haematopoietic stem cells (HSCs) and haematopoietic progenitor cells (HPCs) grow in a specified niche in close association with the microenvironment, the so-called 'haematopoietic niche'. Scaffolds have been introduced to overcome the liquid culture limitations, mimicking the presence of the extracellular matrix (ECM). In the present study the hyaluronic acid scaffold, already developed in the laboratory, has been used for the first time to maintain long-term cultures of CD34⁺ haematopoietic cells obtained from human cord blood. One parameter investigated was the impact on ex vivo survival of CD34⁺ cord blood cells (CBCs) on the hyaluronic acid surface, immobilized with peptides containing the RGD motif. This peptide was conjugated by coating the hyaluronan hydrogel and cultured in serum-free liquid phase complemented with stem cell factor (SCF), a commonly indispensable cytokine for haematopoiesis. Our work demonstrated that these hyaluronan hydrogels were superior to traditional liquid cultures by maintaining and expanding the HPCs without the need for additional cytokines, and a colonization of 280-fold increment in the hydrogel compared with liquid culture after 28 days of ex vivo expansion. Copyright © 2012 John Wiley & Sons, Ltd.

  7. 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.

  8. Umbilical Cord Blood Stem Cells. Who has the right word?

    Directory of Open Access Journals (Sweden)

    Gisela Laporta

    2014-12-01

    Full Text Available In this article we analyze bioethical and legal aspects related to the cryopreservation of cord blood stem cells in Argentina. To unify definitions, the concept and variety of stem cells, together with the understanding of the means to obtain and store umbilical cord blood stem cells, are provided.  Options that arise in our country, mainly analyzing the conceptual differences underlying legal body and parts by public and private biobanks, are described. Additionally, the current Argentinean legislation and circumstances arising from a resolution which INCUCAI sought to regulate private biobanks, is analyzed. This analysis leads to thoughts on the way conflicts are solved when the health and life of people are judicialized. In this particular case, the appearance of a complex new topic which gives rise to new social and healthcare scenarios, must be further understood.

  9. Activation and crosstalk between TNF family receptors in umbilical cord blood cells is not responsible for loss of engraftment capacity following culture.

    Science.gov (United States)

    Mizrahi, Keren; Askenasy, Nadir

    2013-01-01

    Umbilical cord blood (UCB) is a rich source of hematopoietic progenitors for transplantation. Murine and human progenitors are insensitive to apoptotic signaling mediated by the TNF family receptors, however extension of culture over 48 hours is accompanied by severe deterioration in engraftment and hematopoietic reconstituting capacity. In this study we assessed crosstalk between the Fas, TNF and TRAIL receptors, and questioned whether it contributes to increased mortality and decreased activity of UCB progenitors following extended ex vivo culture for 72 hours. The well-characterized TNF-induced expression of Fas is mediated by both TNF receptors, yet the TNF receptors determine survival rather than Fas: superior viability of TNF-R1 progenitors. Additional cross talk includes upregulation of TRAIL-R1 by Fas-ligand, mediated both by fast cycling and inductive crosstalk. These inductive interactions are not accompanied by concomitant sensitization of progenitors to receptor-mediated apoptosis during extended culture, but rather decreased fractional apoptosis in expanded progenitor subsets expressing the receptors. TRAIL upregulates both TRAIL-R1 and TRAIL-R2, accompanied by commensurate susceptibility to spontaneous apoptosis. The current data reveal inductive crosstalk between TNF family receptors, which are largely dissociated from the sensitivity of hematopoietic progenitors to apoptosis. Activation of Fas, TNF and TRAIL receptors and excessive apoptosis are not responsible for loss of engraftment and impaired reconstituting activity of UCB progenitors following extended culture.

  10. Cesarean section imprints cord blood immune cell distributions

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich; Larsen, Jeppe Madura; Rasmussen, Mette Annelie;

    2014-01-01

    Immune programming in early life may affect the risk of developing immune-related diseases later in life. Children born by cesarean section seem to be at higher risk of asthma, allergic rhinitis, and type-1 diabetes. We hypothesized that delivery by cesarean section may affect immune maturation...... in newborns. The objective of the study was to profile innate and adaptive immune cell subsets in cord blood of children born by cesarean section or natural birth....

  11. Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

    Science.gov (United States)

    Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo

    2016-05-18

    The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

  12. Occurrence and transport of synthetic musks in paired maternal blood, umbilical cord blood, and breast milk.

    Science.gov (United States)

    Zhang, Xiaolan; Jing, Ye; Ma, Li; Zhou, Jing; Fang, Xiangming; Zhang, Xinyu; Yu, Yingxin

    2015-01-01

    Although early exposure to environmental pollutants may have important toxicological consequences, the mechanisms of transplacental transfer of synthetic musks are still not well understood. The objective of the present study was to learn the musk contaminations in three matrices, including maternal blood, umbilical cord blood, and breast milk; and investigate their placental transfer mechanisms. The concentrations of eight commonly used synthetic musks were measured in 42 paired samples (126 individual samples in total) of maternal serum, umbilical cord serum, and breast milk from Chinese women living in Shanghai. Musks were ubiquitously detected, especially galaxolide (HHCB) and musk xylene (MX). The total lipid-based concentrations were higher in umbilical cord sera (87.3ng/g), but lower in breast milk (35.2ng/g), compared with maternal serum concentrations (71.2ng/g). There were significant correlations between maternal serum concentrations of HHCBs (HHCB and HHCB-lactone) and umbilical cord serum concentrations, and between maternal serum concentrations and breast milk concentrations (Spearman's rho=0.338-0.597, pumbilical cord sera were >1. And the HHCB-lactone/HHCB ratio in maternal sera was higher compared with umbilical cord sera. Contamination levels were low compared with other regions and HHCBs were found to be the predominant constituents. No regional differences or age-related accumulations were observed. Our study suggests that prenatal exposure to HHCBs occurs and that transplacental transfer is the main route of exposure. Preferential accumulation in umbilical cord blood was observed. The results showed that transplacental transfer of HHCB did not correspond to passive diffusion since the transfer ratios were significantly different from 1. The transfer ratio for HHCB was also larger than that of HHCB-lactone, although HHCB has higher lipid solubility. Low fetal metabolism of HHCB was suggested by the HHCB-lactone/HHCB ratio in maternal and

  13. Effects of Serum from Aplastic Anemia patients on the Expression of Cyclin D3 Isoform in Umbilical Cord Blood CD34+ Cells

    Institute of Scientific and Technical Information of China (English)

    孟凡凯; 谭细友; 刘文励; 孙汉英; 周剑锋; 李春蕊; 刘丹; 何莉; 孙岚

    2004-01-01

    Summary: The pathogenesis of aplastic anemia (AA) was explored and the effects of AA serum on the expression of crucial cyclin D isoform (cyclin D3) in umbilical cord blood hematopoietic stem/progenitor cells were observed. The CD34+ cells were isolated from the cord blood with MIDIMACS Semi-solid methylcellulose culture technique was used to measure the formation of CFUGM;The expression level of cyclin D3 was assayed by semi-quantitative RT-PCR and Western-blot after the hematopoietic stem/progenitor cells were incubated in AA serum. The results showed that the AA serum could inhibit the formation of CFU-GM and down regulate the expression level of the cyclin D3 at the mRNA and protein level respectively. In conclusion, the AA serum could inhibit the proliferation of hematopoietic stem cells and down regulate level of cyclin D3, which might be one mechanism of hematopoiesis inhibition in AA.

  14. Mutation of the NPM1 gene contributes to the development of donor cell-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rodríguez-Macías, Gabriela; Martínez-Laperche, Carolina; Gayoso, Jorge; Noriega, Víctor; Serrano, David; Balsalobre, Pascual; Muñoz-Martínez, Cristina; Díez-Martín, José L; Buño, Ismael

    2013-08-01

    Donor cell leukemia (DCL) is a rare but severe complication after allogeneic stem cell transplantation. Its true incidence is unknown because of a lack of correct recognition and reporting, although improvements in molecular analysis of donor-host chimerism are contributing to a better diagnosis of this complication. The mechanisms of leukemogenesis are unclear, and multiple factors can contribute to the development of DCL. In recent years, cord blood has emerged as an alternative source of hematopoietic progenitor cells, and at least 12 cases of DCL have been reported after unrelated cord blood transplantation. We report a new case of DCL after unrelated cord blood transplantation in a 44-year-old woman diagnosed as having acute lymphoblastic leukemia with t(1;19) that developed acute myeloid leukemia with normal karyotype and nucleophosmin (NPM1) mutation in donor cells. To our knowledge, this is the first report of NPM1 mutation contributing to DCL development.

  15. Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.

    Science.gov (United States)

    Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

    2017-06-01

    Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23-230) and 8.6×10(8) (range 0.7-75×10(8)), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. Copyright© Ferrata Storti Foundation.

  16. Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks

    Science.gov (United States)

    Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T.; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

    2017-01-01

    Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23–230) and 8.6×108 (range 0.7–75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. PMID:28302713

  17. The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential.

    Science.gov (United States)

    Fiorelli, Roberto; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose-Manuel; Raineteau, Olivier

    2013-12-01

    Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self-renewal and multipotential properties in vitro. We demonstrate that a population of GFAP(+) cells that share the morphology and the antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non-proliferative in the intact spinal cord, but incorporate the S-phase marker EdU following spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e., deriving from recombined GFAP-expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self-renewal properties when compared with SVZ-neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co-exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self-renewal properties.

  18. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

    Directory of Open Access Journals (Sweden)

    Sanberg Paul R

    2008-02-01

    Full Text Available Abstract Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

  19. Umbilical cord blood cells for treatment of cerebral palsy; timing and treatment options.

    Science.gov (United States)

    McDonald, Courtney A; Fahey, Michael C; Jenkin, Graham; Miller, Suzanne L

    2017-09-22

    Cerebral palsy is the most common cause of physical disability in children, and there is no cure. Umbilical cord blood (UCB) cell therapy for the treatment of children with cerebral palsy is currently being assessed in clinical trials. While there is much interest in the use of UCB stem cells for neuroprotection and neuroregeneration, the mechanisms of action are not fully understood. Further, UCB contains many stem and progenitor cells of interest, and we will point out that individual cell types within UCB may elicit specific effects. UCB is a clinically proven source of hemotopoietic stem cells (HSCs). It also contains mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs) and immunosupressive cells such as regulatory T cells (Tregs) and monocyte-derived supressor cells. Each of these cell types may be individual candidates for the prevention of brain injury following hypoxic and inflammatory events in the perinatal period. We will discuss specific properties of cell types in UCB, with respect to their therapeutic potential and the importance of optimal timing of administration. We propose that tailored cell therapy and targeted timing of administration will optimise results for future clinical trials in the neuroprotective treatment of perinatal brain injury.Pediatric Research accepted article preview online, 22 September 2017. doi:10.1038/pr.2017.236.

  20. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

    Science.gov (United States)

    Bachstetter, Adam D; Pabon, Mibel M; Cole, Michael J; Hudson, Charles E; Sanberg, Paul R; Willing, Alison E; Bickford, Paula C; Gemma, Carmelina

    2008-01-01

    Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain. PMID:18275610

  1. Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

    Science.gov (United States)

    Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

    2016-09-05

    The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans.

  2. Surfactant Protein D Levels in Umbilical Cord Blood and Capillary Blood of Premature Infants

    DEFF Research Database (Denmark)

    Dahl, Marianne; Holmskov, Uffe; Husby, Steffen

    2006-01-01

    of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant...

  3. 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.

  4. Effective Action Distance of Co-Culture between Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells and Human Adipose Derived Stem Cells%脐血造血干/祖细胞与脂肪干细胞共培养的作用距离研究

    Institute of Scientific and Technical Information of China (English)

    宋克东; 崔占峰; 刘天庆; 武爽; 郭文华; 郝永杰; 方美云; 石芳鑫; 朱丽丽; 马学虎

    2011-01-01

    设计了一种细胞间距可调的transwell共培养方法,以研究脐带血来源的造血干/祖细胞(HS/PCs)和人脂肪干细胞(human-adipose derived stem cells,h-ADSCs)体外共培养时细胞间作用距离对造血干细胞扩增能力和脂肪干细胞在共培养后干细胞特性的影响.采用不同规格的砂纸打磨孔板的上壁面,经高精度游标卡尺测量,使两种细胞之间的有效接触间距为10~450 μm不等.然后以h-ADSCs为基质细胞,分别考察HS/PCs和h-ADSCs在不同的作用距离下的共培养情况.其间每24小时对细胞进行计数,观察细胞形态.培养7天后对MNCs表面抗原CD34+、CFU-GM集落扩增倍数进行了检测;同时也对h-ADSCs表面抗原(CD13、CD29、CD34、CD44、CD45、CD73、CD105、CD166、HLA-DR)及其多向分化潜能(成骨、成软骨、成脂肪)进行分析以鉴定其干细胞性能.结果表明,通过transwell共培养,细胞之间在作用距离为350μm时HS/PCs的扩增效果最好,其中造血MNCs扩增了15.1±0.2倍,CD34+扩增了5.0±0.1倍;扩增的h-ADSCs表达CD29、CD44、CD166,而不表达CD34、CD45,且在适当诱导条件下可以向成骨细胞、软骨细胞、脂肪细胞分化.%In order to investigate the effects of in vitro co-culture distance between umbilical cord blood-derived hematopoietic stem/progenitor cells (HS/PCs) and human adipose derived stem cells (h-ADSCs) on the expansion of HS/PCs and the stem cell properties of h-ADSCs, a novel transwell co-culture protocol in which the distance between the two culture chambers could be adjusted was designed. Sand papers with different specifications were utilized to adjust the cellular action distance between two kinds of cells mentioned above in the range of 10 to 450 μrn which was measured by a high-precision vernier caliper. Then the HS/PCs were cultured in the modified transwell supported by ADSCs for 7 days. The total cell number was counted by using a hemacytometer and the cell morphology

  5. Maternal Body-Mass Index and Cord Blood Circulating Endothelial Colony-Forming Cells

    Science.gov (United States)

    Lin, Ruei-Zeng; Miranda, Maria L.; Vallejo-Vaz, Antonio J.; Stiefel, Pablo; Praena-Fernández, Juan M.; Bernal-Bermejo, Jose; Jimenez-Jimenez, Luis M.; Villar, Jose; Melero-Martin, Juan M.

    2013-01-01

    Objective Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that are particularly abundant in umbilical cord blood. We sought to determine whether ECFC abundance in cord blood is associated with maternal body-mass index (BMI) in non-pathological pregnancies. Study design We measured the level of ECFCs in the cord blood of neonates (n=27) born from non-obese healthy mothers with non-pathological pregnancies and examined whether ECFC abundance correlated with maternal BMI. We also examined the effect of maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic assays. Results We observed variation in ECFC abundance among subjects and found a positive correlation between pre-pregnancy maternal BMI and ECFC content (r=0.51, P=0.007), which was independent of other obstetric factors. Despite this variation, ECFC phenotype and functionality were deemed normal and highly similar between subjects with maternal BMI <25 kg/m2 and BMI between 25–30 kg/m2, including the ability to form vascular networks in vivo. Conclusions This study underlines the need to consider maternal BMI as a potential confounding factor for cord blood levels of ECFCs in future comparative studies between healthy and pathological pregnancies. Endothelial colony-forming cells (ECFCs) are a subset of progenitor cells that circulate in peripheral blood and can give rise to endothelial cells (1,2), contributing to the formation of new vasculature and the maintenance of vascular integrity (3–5). The mechanisms that regulate the abundance of these cells in vivo remain poorly understood. ECFCs are rare in adult peripheral blood (1,2,10). In contrast, there is an elevated number of these cells in fetal blood during the third trimester of pregnancy (11–13). Emerging evidence indicates that deleterious conditions during fetal life can impair ECFC content and function. For instance, offspring of diabetic mothers have been shown to have

  6. Cord blood IgE. I. IgE screening in 2814 newborn children

    DEFF Research Database (Denmark)

    Hansen, L G; Høst, A; Halken, S;

    1992-01-01

    Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l were......E values in the autumn was found. No correlation between cord blood IgE and birth weight or gestational age was demonstrated. Only few newborns had cord blood IgA values greater than 0.014 g/l, calculated as geometric mean cord blood IgA + 2 SD among children with no detectable cord blood IgE, indicating...

  7. Blood gas values in clamped and unclamped umbilical cord at birth.

    Science.gov (United States)

    Di Tommaso, Mariarosaria; Seravalli, Viola; Martini, Irene; La Torre, Pasquale; Dani, Carlo

    2014-09-01

    To determine the reliability of the cord blood gas analysis on the unclamped cord compared to the standard technique of sampling on double clamped cord. Prospective observational study conducted on 46 singleton neonates vaginally delivered at term. Matched pairs of umbilical artery and vein blood samples were collected from unclamped cord within 90s after birth and from the same cord after clamping, with the clamping occurring immediately after the first blood collection. A blood gas analysis was performed on each collected sample. Arterial and venous blood samples were analyzed for pH, PO2, pCO2, SaO2, hemoglobin concentration (ctHb) and base excess (BE). The values were compared between the two groups (clamped vs unclamped) using a Wilcoxon test. No significant difference was found in pH, PO2, pCO2, SaO2 and ctHb values on arterial blood between unclamped and clamped cord. The only significant difference was related to BE (pblood, the values of pH, PO2, pCO2 were comparable between unclamped and clamped cord, while the values of SaO2, ctHb and BE were significantly different (pblood gas parameters and in the main venous blood gas parameters between unclamped and clamped cord. Sampling of cord blood for gas analysis may be performed on the unclamped cord right after birth without reducing the accuracy of the analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells

    Directory of Open Access Journals (Sweden)

    Thomas Bart

    2010-10-01

    Full Text Available Thomas BartSwiss Blood Stem Cells, Bern, SwitzerlandAbstract: Umbilical cord blood (CB has become, since its first successful use more than two decades ago, an increasingly important source of blood stem cells. In this light, an overview of current usage of CB in the field of unrelated hematopoietic blood stem cell transplantation (HSCT is given. The three main sources of hematopoietic stem cells: bone marrow (BM, peripheral blood stem cells (PBSC, and cord blood (CB are compared as regards their current quantitative usage in HSCT. A cost analysis of the named three hematopoietic blood stem cell (HSC sources, taking into account various factors, is undertaken. The health economical comparison shows significant differences between CB on the one side, and BM and PBSC on the other. The consequences for the public health side and propositions for a possible health care policy, especially regarding future resource allocation towards the different choices for HSCT products, are discussed. An outlook on the possible future usage of BM, PBSC, and CB and its implications on health systems, donor registries, and CB banks is given.Keywords: health economy, cord blood, hematopoietic stem cell transplantation

  9. Lamotrigine in pregnancy - therapeutic drug monitoring in maternal blood, amniotic fluid, and cord blood.

    Science.gov (United States)

    Paulzen, Michael; Lammertz, Sarah E; Veselinovic, Tanja; Goecke, Tamme W; Hiemke, Christoph; Gründer, Gerhard

    2015-09-01

    This study is the first to measure and correlate lamotrigine concentrations in maternal blood, amniotic fluid, and umbilical cord blood and account for distribution of the drug between these three compartments. Concentrations of lamotrigine were measured in six mother-infant pairs at the time of delivery. Daily doses of lamotrigine ranged between 200 and 650 mg. Daily doses were correlated with maternal serum and umbilical cord blood concentrations, and serum levels were correlated with levels in amniotic fluid. Lamotrigine levels in serum correlated strongly with the lamotrigine levels in amniotic fluid (r=+0.986, Pamniotic fluid was in a range between 0.31 and 0.75 (mean 0.58, SD 0.17); the penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood levels, was found to be in a range between 0.48 and 1.27 (mean 0.81, SD 0.28). Lamotrigine concentrations in amniotic fluid provided evidence that maternally administered lamotrigine is accessible to the fetus in a manner not previously appreciated. Furthermore, the penetration ratio into umbilical cord blood calculated here is in line with the largest study carried out so far to explore transplacental transfer.

  10. Cord blood 25(OH)-vitamin D deficiency and childhood asthma, allergy and eczema

    DEFF Research Database (Denmark)

    Chawes, Bo L; Bønnelykke, Klaus; Jensen, Pia F

    2014-01-01

    with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors. CONCLUSION: Cord blood 25(OH)-Vitamin D deficiency associated with increased risk...... function and sensitization were performed repeatedly from birth. RESULTS: After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (

  11. 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

  12. Cord Blood as a Source of Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Rohtesh S Mehta

    2016-01-01

    Full Text Available Cord blood (CB offers several unique advantages as a graft source for hematopoietic stem cell transplantation (HSCT. The risk of relapse and graft-versus-host disease (GVHD after cord blood transplantation (CBT are lower than what is typically observed after other graft sources with a similar degree of human leukocyte antigen (HLA mismatch. Natural killer (NK cells have a well-defined role in both innate and adaptive immunity and as the first lymphocytes to reconstitute after HSCT and CBT, they play a significant role in protection against early relapse. In this article, we highlight the uses of CB NK cells in transplantation and adoptive immunotherapy. First, we will describe differences in the phenotype and functional characteristics of NK cells in CB as compared with peripheral blood. Then, we will review some of the obstacles we face in using resting CB NK cells for adoptive immunotherapy, and discuss methods to overcome them. We will review the current literature on killer-cell immunoglobulin-like receptors (KIR-ligand mismatch and outcomes after CBT. Finally, we will touch on current strategiesfor the use of CB NK cells in cellular immunotherapy.

  13. Cord Blood as a Source of Natural Killer Cells

    Science.gov (United States)

    Mehta, Rohtesh S.; Shpall, Elizabeth J.; Rezvani, Katayoun

    2016-01-01

    Cord blood (CB) offers several unique advantages as a graft source for hematopoietic stem cell transplantation (HSCT). The risk of relapse and graft vs. host disease after cord blood transplantation (CBT) is lower than what is typically observed after other graft sources with a similar degree of human leukocyte antigen mismatch. Natural killer (NK) cells have a well-defined role in both innate and adaptive immunity and as the first lymphocytes to reconstitute after HSCT and CBT, and they play a significant role in protection against early relapse. In this article, we highlight the uses of CB NK cells in transplantation and adoptive immunotherapy. First, we will describe differences in the phenotype and functional characteristics of NK cells in CB as compared with peripheral blood. Then, we will review some of the obstacles we face in using resting CB NK cells for adoptive immunotherapy, and discuss methods to overcome them. We will review the current literature on killer-cell immunoglobulin-like receptors ligand mismatch and outcomes after CBT. Finally, we will touch on current strategies for the use of CB NK cells in cellular immunotherapy. PMID:26779484

  14. Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Hyung Joon; Seo, Ha-Rim [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Jeong, Hyo Eun [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Choi, Seung-Cheol; Park, Jae Hyung; Yu, Cheol Woong; Hong, Soon Jun [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Chung, Seok [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Lim, Do-Sun, E-mail: dslmd@kumc.or.kr [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Two distinct vascular progenitor cells are induced from adult peripheral blood. • ECFCs induce vascular structures in vitro and in vivo. • SMPCs augment the in vitro and in vivo angiogenic potential of ECFCs. • Both cell types have synergistic therapeutic potential in ischemic hindlimb model. - Abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.

  15. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  16. Pregnancy hypertension and umbilical cord blood lead levels

    Energy Technology Data Exchange (ETDEWEB)

    Rabinowitz, M.; Bellinger, D.; Leviton, A. (Children' s Hospital, Boston, MA (USA)); Needleman, H. (Children' s Hospital, Pittsburgh, PA (USA)); Schoenbaum, S. (Harvard Community Health Plan, Brookline Village, MA (USA))

    Pregnancy hypertension, blood pressure during labor, and the umbilical cord blood lead concentration were assessed in 3,851 women for whom additional demographic, medical, and personal information was available. Lead levels correlated with both systolic and diastolic blood pressure during labor. The incidence of clinically defined pregnancy hypertension, nearly 11% overall, increased with lead level. A series of multivariate models of pregnancy hypertension and of systolic blood pressure as a function of maternal age, parity, hematocrit, ponderal index, race, season, and diabetes were improved by including lead as a predictor variable. These other risk factors are not affected by the lead term. The relative risk for pregnancy hypertension doubles when lead increases from 2 to 15 {mu}g/dl. The effect is statistically strong, with a magnitude of about 3 mm for a 10 {mu}g/dl range, about the same magnitude associated with diabetes. At these observed levels (mean blood lead = 6.0 {mu}g/dl, SD = 3.3, range 0 > 35), not currently recognized as overtly toxic, lead has a small but demonstrable association with pregnancy hypertension and blood pressure at the time of delivery, but not with pre-eclampsia nor toxemia. Although this association is not likely to influence the clinical management of hypertension, it indicates that lead at typical contemporary urban levels, does effect multiple physiological functions.

  17. A comparative study of the protein C system in mother's blood, cord blood and amniotic fluid.

    OpenAIRE

    Ewa Zekanowska; Waldemar Uszyński; Mieczysław Uszyński; Jarosław Kuczyński; Marek Szymański

    2010-01-01

    Activated protein C (APC) is an important anticoagulant which plays a role in pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental circulation and development of the fetus as well as in pathogenesis of preeclampsia. The study objective was to compare the levels of the respective components of the protein C system (protein C, PC; protein S, PS; thrombomodulin, TM) as well as thrombin activatable fibrinolysis inhibitor - TAFI in mother's blood, cord blood and amniotic fluid. ...

  18. Good practices in collecting umbilical cord and placental blood.

    Science.gov (United States)

    Lopes, Lauren Auer; Bernardino, Elizabeth; Crozeta, Karla; Guimarães, Paulo Ricardo Bittencourt

    2016-08-18

    to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1) verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2) definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r) and R(r). while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality. identificar fatores relacionados à qualidade das amostras do sangue de cordão umbilical e placentário e definir boas práticas para sua coleta em um banco público de sangue de cordão umbilical e placentário. pesquisa descritiva, abordagem quantitativa, realizada em um banco público de sangue de cordão umbilical e placentário, desenvolvida em duas etapas: 1) verificação dos fatores obstétricos, neonatais e operacionais, obtidos por coleta em instrumento próprio e observação não participante; 2) definição das boas práticas, por meio do agrupamento de não-conformidades observadas antes, durante e após a coleta do sangue. Os dados foram analisados por meio da estatística descritiva, utilizando-se dos softwares Statistica(r) e R(r). houve

  19. 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.

  20. Improving engraftment and immune reconstitution in umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Robert eDanby

    2014-02-01

    Full Text Available Umbilical cord blood (UCB is an important source of haematopoietic stem cells (HSC for allogeneic transplantation when HLA-matched sibling and unrelated donors (MUD are unavailable. Although the overall survival rates of UCB transplantation are comparable to the results with MUD, UCB transplants are associated with slow engraftment, delayed immune reconstitution, and increased opportunistic infections. While this may be a consequence of the lower cell dose in UCB grafts, it also reflects the relative immaturity of cellular immunity within cord blood. Furthermore, the limited number of cells and the non-availability of donor lymphocyte infusions (DLI currently prevent the use of post-transplant cellular immunotherapy to boost donor-derived immunity to treat infection, mixed chimerism and disease relapse. Therefore, to further develop UCB transplantation, many strategies to enhance engraftment and immune reconstitution are currently under investigation. This review summarises our current understanding of engraftment and immune recovery following UCB transplantation and why this differs from allogeneic transplants using other sources of HSC. It also provides an comprehensive overview of the promising techniques being used to improve myeloid and lymphoid recovery, including expansion, homing, and delivery of UCB HSC; combined use of UCB with third party donors; isolation and expansion of NK cells, pathogen specific T cells, and regulatory T cells; methods to protect and/or improve thymopoiesis. As many of these strategies are now in clinical trials, it is anticipated that UCB transplantation will continue to advance, further expanding our understanding of UCB biology and HSC transplantation.

  1. Novel Techniques for Ex Vivo Expansion of Cord Blood: Clinical Trials

    Directory of Open Access Journals (Sweden)

    Rohtesh S Mehta

    2015-12-01

    Full Text Available Cord blood (CB provides an excellent alternative source of hematopoietic progenitor cells (HPC for patients lacking human leukocyte antigen (HLA-matched peripheral blood or bone marrow graft for transplantation. However, due to the limited cell dose in CB graft, it is associated with prolonged time to engraftment, risk of graft rejection, infections and treatment-related mortality. To increase the cell dose, a variety of ex vivo expansion techniques have been developed. Results of traditional methods of CB expansion using cytokines alone were disappointing. Expanding CB cells with mesenchymal progenitor cells led to sizeable increase in graft content and improved engraftment. Other methods used HPC-differentiation blockers, such as nicotinamide analogs, copper chelators, inducing constitutive Notch signaling, or an aryl hydrocarbon receptor antagonist (StemReginin1. Many of these methods lead to substantial expansions of total nucleated cells and CD34+ cells, and significantly improved time to neutrophil or platelet engraftment in patients transplanted with the expanded products compared to the recipients of unmanipulated CBT. These studies differ not only in the expansion method, but also with regards to the cytokines used, patient population, conditioning regimens and transplantation practices, to name a few. Some of these methods employed expansion of a portion of CB unit in the setting of single CBT, while others in the setting of double CBT. Here, we review various procedures used for CB expansion and highlight some of the key differences. Novel methods of improving engraftment that aim at improving bone marrow homing potential of CB cells are not reviewed.

  2. Umbilical cord blood banks. Ethical aspects. Public versus private banks.

    Science.gov (United States)

    Aznar Lucea, Justo

    2012-01-01

    The creation of umbilical cord blood (UCB) banks raises interesting medical, social, economic and ethical issues. This paper reviews the ethical problems specifically. In this respect, it evaluates: a) whether there are advantages to the use of UCB compared to bone marrow, b) whether or not it is ethical to create UCB banks, c) whether their creation is ethically acceptable in terms of their clinical usefulness or d) the use made of them for therapeutic purposes, and finally e) whether their creation is ethically justified from a cost/profitability point of view. We focus primarily on evaluating the ethical controversy between public and private banks, particularly on whether it is ethical to bank autologous blood in private UCB banks, on the basis of its limited possibilities for use by the cord blood donor. We can conclude that, from an ethical point of view, autologous blood banks have limited acceptance among specialised researchers, scientific societies and other public institutions. Therefore, we believe that it is ethically more acceptable to support the creation of public UCB banks for medical and social reasons and, above all, based on the principle of justice and human solidarity. Nevertheless, there is no definitive ethical argument why a couple, according to their autonomy and freedom, cannot bank their child's UCB in a private bank. An equally acceptable solution could be the creation of mixed banks, such as that proposed by the Virgin Health Bank or like the Spanish system where autologous samples can be stored in public banks but with the proviso that if at any time the stored sample is required by any person other than the donor, it would have to be given to them.

  3. 3-D refractive index tomograms and deformability of individual human red blood cells from cord blood of newborn infants and maternal blood

    CERN Document Server

    Park, HyunJoo; Kim, Kyoohyun; Lee, Sangyun; Kook, Songyi; Lee, Dongheon; Suh, In Bum; Nab, Sunghun; Park, YongKeun

    2015-01-01

    Red blood cells (RBCs) from the cord blood of newborn infants have distinctive functions for fetal and infant development. To systematically investigate the biophysical characteristics of individual cord RBCs in newborn infants, a comparative study was performed of RBCs from cord blood of newborn infants, and of adult RBCs from mothers or non-pregnant women, employing optical holographic micro-tomography. Optical measurements of 3-D refractive index distributions, and of dynamic membrane fluctuations of individual RBCs, enabled retrieval of the morphological, biochemical, and mechanical properties of cord, maternal, and adult RBCs at the individual cell level. The volume and surface area of the cord RBCs were significant larger than those of RBCs from non-pregnant women, and cord RBCs have more flattened shapes than RBCs in adults. In addition, the Hb content in the cord RBCs of newborns was significantly greater. The Hb concentration in cord RBCs was higher than for non-pregnant women or maternal RBCs, but t...

  4. Institutional Knots: A Comparative Analysis of Cord Blood Policy in Canada and the United States.

    Science.gov (United States)

    Denburg, Avram

    2016-02-01

    Umbilical cord blood is a rich source of blood stem cells, which are of critical clinical importance in the treatment of a variety of malignant and genetic conditions requiring stem cell transplantation. Many countries have established national public cord blood banks; such banks often coexist with a panoply of private options for cord blood banking. Until recently, Canada was the only G8 country without a national cord blood bank. This differs markedly from the United States, which years ago established a national cord blood bank policy and inventory. This article investigates potential reasons for this discrepancy through a comparative analysis of the evolution of programs and policies on national cord blood banking in Canada and the United States. My analysis suggests that cross-national discrepancies in policy on public cord blood banking were determined primarily by institutional factors, principal among them formal governmental structure and the legacy of past policies. Institutional entrepreneurialism in the health sector played a constitutive role in the earlier evolution of national cord blood policy in the United States as compared to Canada.

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  13. 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.

  14. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells.

    Science.gov (United States)

    Sanberg, Paul R; Eve, David J; Willing, Alison E; Garbuzova-Davis, Svitlana; Tan, Jun; Sanberg, Cyndy D; Allickson, Julie G; Cruz, L Eduardo; Borlongan, Cesar V

    2011-01-01

    Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

  15. The High Yield Expansion and Megakaryocytic Differentiation of Human Umbilical Cord Blood CD133+ Cells

    Directory of Open Access Journals (Sweden)

    Mahin Nikougoftar Zarif

    2011-01-01

    Full Text Available Objective: Despite of many benefits, umbilical cord blood (UCB hematopoietic stem cell(HSC transplantation is associated with low number of stem cells and slow engraftment;in particular of platelets. So, expanded HSCs and co-transfusion of megakaryocyte (MKprogenitor cells can shorten this period. In this study, we evaluated the cytokine conditionsfor maximum expansion and MK differentiation of CD133+ HSCs.Materials and Methods: In this experimental study, The CD133+ cells were separatedfrom three cord blood samples by magnetic activated cell sorting (MACS method, expandedin different cytokine combinations for a week and differentiated in thrombopoietin(TPO for the second week. Differentiation was followed by the flow cytometry detectionof CD41 and CD61 surface markers. Colony forming unit (CFU assay and DNA analysiswere done for colonogenic capacity and ploidy assay.Results: CD133+ cells showed maximum expansion in the stem span medium with stemcell factor (SCF + FMS-like tyrosine kinase 3-ligand (Flt3-L + TPO but the maximum differentiationwas seen when CD133+ cells were expanded in stem span medium with SCF+ Interleukin 3 (IL-3 + TPO for the first and in TPO for the second week. Colony FormingUnit-MK (CFU-MK was formed in three sizes of colonies in the mega-cult medium. In theDNA analysis; 25.2 ± 6.7% of the cells had more than 2n DNA mass.Conclusion: Distinct differences in the MK progenitor cell count were observed when thecells were cultured in stem span medium with TPO, SCF, IL-3 and then the TPO in thesecond week. Such strategy could be applied for optimization of CD133+ cells expansionfollowed by MK differentiation.

  16. Reconstruction of hematopoietic inductive microenvironment after transplantation of VCAM-1-modified human umbilical cord blood stromal cells.

    Directory of Open Access Journals (Sweden)

    Yao Liu

    Full Text Available The hematopoietic inductive microenvironment (HIM is where hematopoietic stem/progenitor cells grow and develop. Hematopoietic stromal cells were the key components of the HIM. In our previous study, we had successfully cultured and isolated human cord blood-derived stromal cells (HUCBSCs and demonstrated that they could secret hemopoietic growth factors such as GM-CSF, TPO, and SCF. However, it is still controversial whether HUCBSCs can be used for reconstruction of HIM. In this study, we first established a co-culture system of HUCBSCs and cord blood CD34(+ cells and then determined that using HUCBSCs as the adherent layer had significantly more newly formed colonies of each hematopoietic lineage than the control group, indicating that HUCBSCs had the ability to promote the proliferation of hematopoietic stem cells/progenitor cells. Furthermore, the number of colonies was significantly higher in vascular cell adhesion molecule-1 (VCAM-1-modified HUCBSCs, suggesting that the ability of HUCBSCs in promoting the proliferation of hematopoietic stem cells/progenitor cells was further enhanced after having been modified with VCAM-1. Next, HUCBSCs were infused into a radiation-damaged animal model, in which the recovery of hematopoiesis was observed. The results demonstrate that the transplanted HUCBSCs were "homed in" to bone marrow and played roles in promoting the recovery of irradiation-induced hematopoietic damage and repairing HIM. Compared with the control group, the HUCBSC group had significantly superior effectiveness in terms of the recovery time for hemogram and myelogram, CFU-F, CFU-GM, BFU-E, and CFU-Meg. Such differences were even more significant in VCAM-1-modified HUCBSCs group. We suggest that HUCBSCs are able to restore the functions of HIM and promote the recovery of radiation-induced hematopoietic damage. VCAM-1 plays an important role in supporting the repair of HIM damage.

  17. Background and future considerations for human cord blood hematopoietic cell transplantation, including economic concerns.

    Science.gov (United States)

    Broxmeyer, Hal E; Farag, Sherif

    2013-12-01

    Cord blood (CB) has been used since 1988 as a source of hematopoietic stem cells (HSCs) and progenitor cells for hematopoietic cell transplantation (HCT) to treat patients with malignant and nonmalignant disorders. CB has both advantages and disadvantages when compared with other tissue sources of HSCs such as bone marrow and mobilized peripheral blood, which are also being used in the setting of HCT. This short review focuses on some historical information, as well as current efforts that are being assessed to enhance the efficacy of CB HCT. Also of importance are the costs of CB, and the feasibility and economics of using such to be identified, and newly confirmed improvements worldwide for the greatest number of patients. In this context, simple methods that would not necessarily entail the need for selected cell-processing facilities to ex vivo expand or improve the CB graft's functional activity may be of interest, with one such possibility being the use of an orally active inhibitor of the enzyme dipeptidylpeptidase 4, alone or in combination with other new and innovative approaches for improving HSC engraftment and in vivo repopulating capability of CB.

  18. Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies.

    Science.gov (United States)

    Nishihira, H; Toyoda, Y; Miyazaki, H; Kigasawa, H; Ohsaki, E

    1996-01-01

    We investigated the effects of recombinant human thrombopoietin (rhTPO) on the growth of megakaryocytic (MK) colony derived MK progenitors from human cord blood (CB) in vitro and the effects of gestational age on the number of MK colonies. The results demonstrated that rhTPO alone supports the growth of MK colonies and induces not only proliferation but also differentiation of MK progenitors. CB shows a high frequency of MK colonies; most of which are very large and equivalent to high proliferative potential colony-forming unit-megakaryocyte. The colonies could be macroscopically observed as white spots in the culture dish. Preterm neonates showed greater numbers of MK progenitors than term neonates and there was an inverse correlation between gestational age and concentration of MK progenitors of CB. The effects of gestational age was an important factor on the proliferative capacity of MK progenitors and on the response to rhTPO.

  19. Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

    Science.gov (United States)

    Screnci, Maria; Murgi, Emilia; Valle, Veronica; Tamburini, Anna; Pellegrini, Maria Grazia; Strano, Sabrina; Corona, Francesca; Ambrogi, Eleonora Barbacci; Girelli, Gabriella

    2016-03-01

    Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

  20. Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city.

    Science.gov (United States)

    Barbieri, Flavia L; Gardon, Jacques; Ruiz-Castell, María; Paco V, Pamela; Muckelbauer, Rebecca; Casiot, Corinne; Freydier, Rémi; Duprey, Jean-Louis; Chen, Chih-Mei; Müller-Nordhorn, Jacqueline; Keil, Thomas

    2016-01-01

    This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Niño birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient = 0.59; p toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.

  1. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Luigi Aloe; Patrizia Bianchi; Alberto De Bellis; Marzia Soligo; Maria Luisa Rocco

    2014-01-01

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

  2. US Public Cord Blood Banking Practices: Recruitment, Donation, and the Timing of Consent

    Science.gov (United States)

    Broder, Sherri; Ponsaran, Roselle; Goldenberg, Aaron

    2012-01-01

    BACKGROUND Cord blood has moved rapidly from an experimental stem cell source to an accepted and important source of hematopoietic stem cells. There has been no comprehensive assessment of US public cord blood banking practices since the Institute of Medicine study in 2005. STUDY DESIGN AND METHODS Of 34 US public cord blood banks identified, 16 participated in our qualitative survey of public cord blood banking practices. Participants took part in in-depth telephone interviews in which they were asked structured and open-ended questions regarding recruitment, donation, and the informed consent process at these banks. RESULTS 13 of 16 participants reported a variably high percentage of women who consented to public cord blood donation. 15 banks offered donor registration at the time of hospital admission for labor and delivery. 7 obtained full informed consent and medical history during early labor and 8 conducted some form of phased consent and/or phased medical screening and history. 9 participants identified initial selection of the collection site location as the chief mode by which they recruited minority donors. CONCLUSION Since 2005, more public banks offer cord blood donor registration at the time of admission for labor and delivery. That, and the targeted location of cord blood collection sites, are the main methods used to increase access to donation and HLA diversity of banked units. Currently, the ability to collect and process donations, rather than donor willingness, is the major barrier to public cord blood banking. PMID:22803637

  3. Umbilical cord blood lactate: a valuable tool in the assessment of fetal metabolic acidosis

    DEFF Research Database (Denmark)

    Gjerris, Anne Cathrine Roslev; Staer-Jensen, Jette; Jørgensen, Jan Stener

    2008-01-01

    The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and pH, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal asphyxia using...

  4. Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Kazuya Yokota

    2015-08-01

    Full Text Available Neural stem/progenitor cell (NSPC transplantation is a promising therapeutic strategy for spinal cord injury (SCI. However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, but not after severe SCI. In severe SCI mice, there were few remaining host neurons within the range of NSPC engraftment; thus, we examined whether the co-distribution of transplant and host is a contributory factor for functional improvement. A cellular selective analysis using laser microdissection revealed that drug-induced host neuronal ablation considerably decreased the synaptogenic potential of the engrafted NSPCs. Furthermore, following host neuronal ablation, neuronal retrograde tracing showed less propriospinal relay connections bridging the lesion after NSPC transplantation. Our findings suggest that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery, providing significant insight for establishing therapeutic strategies for severe SCI.

  5. The relationship between fetal biophysical profile and cord blood PH

    Directory of Open Access Journals (Sweden)

    Valadan M

    2009-02-01

    Full Text Available "nBackground: The Biophysical Profile (BPP is a noninvasive test that predicts the presence or absence of fetal asphyxia and, ultimately, the risk of fetal death in the antenatal period. Intervention on the basis of an abnormal biophysical profile result has been reported to yield a significant reduction in prenatal mortality, and an association exists between biophysical profile scoring and a decreased cerebral palsy rate in a given population. The BPP evaluates five characteristics: fetal movement, tone, breathing, heart reactivity, and amniotic fluid (AF volume estimation. The purpose of study was to determine whether there are different degree of acidosis at which the biophysical activity (acute marker are affected. "nMethods: In a prospective study of 140 patients undergoing cesarean section before onset of labor, the fetal biophysical profile was performed 24h before the time of cesarean and was matched with cord arterial PH that was obtained from a cord segment (10-20cm that was double clamped after delivery of newborn. (using cord arterial PH less than 7.20 for the diagnosis of acidosis. "nResults: The fetal biophysical profile was found to have a significant relationship with umbilical blood PH. The sensitivity, specificity, positive predictive value, negative predictive value of fetal biophysical profile score were: 88.9%, 88.6%, 50%, 98.1%. "nConclusion: The first manifestations of fetal acidosis are nonreactive nonstress testing and fetal breathing loss; in advanced acidemia fetal movements and fetal tone are compromised. A protocol of antepartum fetal evaluation is suggested based upon the individual biophysical components rather than the score alone.

  6. Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia.

    Science.gov (United States)

    Crompton, Kylie E; Elwood, Ngaire; Kirkland, Mark; Clark, Pamela; Novak, Iona; Reddihough, Dinah

    2014-07-01

    Umbilical cord blood may have therapeutic benefit in children with cerebral palsy (CP), but further studies are required. On first appearance it seems that Australia is well placed for such a trial because we have excellence in CP research backed by extensive CP registers, and both public and private cord blood banks. We aimed to examine the possibilities of conducting a trial of autologous umbilical cord blood cells (UCBCs) as a treatment for children with CP in Australia. Data linkages between CP registers and cord blood banks were used to estimate potential participant numbers for a trial of autologous UCBCs for children with CP. As of early 2013, one Victorian child with CP had cord blood stored in the public bank, and between 1 and 3 children had their cord blood stored at Cell Care Australia (private cord blood bank). In New South Wales, we counted two children on the CP register who had their stored cord blood available in early 2013. We estimate that there are between 10 and 24 children with CP of any type who have autologous cord blood available across Australia. In nations with small populations like Australia, combined with Australia's relatively low per capita cord blood storage to date, it is not currently feasible to conduct trials of autologous UCBCs for children with CP. Other options must be explored, such as allogeneic UCBCs or prospective trials for neonates at risk of CP. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  7. 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.

  8. 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.

  9. Cord Blood DNA Methylation Biomarkers for Predicting Neurodevelopmental Outcomes

    Directory of Open Access Journals (Sweden)

    Nicolette A. Hodyl

    2016-12-01

    Full Text Available Adverse environmental exposures in pregnancy can significantly alter the development of the fetus resulting in impaired child neurodevelopment. Such exposures can lead to epigenetic alterations like DNA methylation, which may be a marker of poor cognitive, motor and behavioral outcomes in the infant. Here we review studies that have assessed DNA methylation in cord blood following maternal exposures that may impact neurodevelopment of the child. We also highlight some key studies to illustrate the potential for DNA methylation to successfully identify infants at risk for poor outcomes. While the current evidence is limited, in that observations to date are largely correlational, in time and with larger cohorts analyzed and longer term follow-up completed, we may be able to develop epigenetic biomarkers that not only indicate adverse early life exposures but can also be used to identify individuals likely to be at an increased risk of impaired neurodevelopment even in the absence of detailed information regarding prenatal environment.

  10. Cesarean section imprints cord blood immune cell distributions

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich; Larsen, Jeppe Madura; Rasmussen, Mette Annelie

    2014-01-01

    Immune programming in early life may affect the risk of developing immune-related diseases later in life. Children born by cesarean section seem to be at higher risk of asthma, allergic rhinitis, and type-1 diabetes. We hypothesized that delivery by cesarean section may affect immune maturation i...... in newborns. The objective of the study was to profile innate and adaptive immune cell subsets in cord blood of children born by cesarean section or natural birth.......Immune programming in early life may affect the risk of developing immune-related diseases later in life. Children born by cesarean section seem to be at higher risk of asthma, allergic rhinitis, and type-1 diabetes. We hypothesized that delivery by cesarean section may affect immune maturation...

  11. It Is All in the Blood: The Multifaceted Contribution of Circulating Progenitor Cells in Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Gian Paolo Fadini

    2012-01-01

    Full Text Available Diabetes mellitus (DM is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs along with excess smooth muscle progenitor (SMP and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.

  12. A Hydrogel Bridge Incorporating Immobilized Growth Factors and Neural Stem/Progenitor Cells to Treat Spinal Cord Injury.

    Science.gov (United States)

    Li, Hang; Ham, Trevor R; Neill, Nicholas; Farrag, Mahmoud; Mohrman, Ashley E; Koenig, Andrew M; Leipzig, Nic D

    2016-04-06

    Spinal cord injury (SCI) causes permanent, often complete disruption of central nervous system (CNS) function below the damaged region, leaving patients without the ability to regenerate lost tissue. To engineer new CNS tissue, a unique spinal cord bridge is created to deliver stem cells and guide their organization and development with site-specifically immobilized growth factors. In this study, this bridge is tested, consisting of adult neural stem/progenitor cells contained within a methacrylamide chitosan (MAC) hydrogel and protected by a chitosan conduit. Interferon-γ (IFN-γ) and platelet-derived growth factor-AA (PDGF-AA) are recombinantly produced and tagged with an N-terminal biotin. They are immobilized to streptavidin-functionalized MAC to induce either neuronal or oligodendrocytic lineages, respectively. These bridges are tested in a rat hemisection model of SCI between T8 and T9. After eight weeks treatments including chitosan conduits result in a significant reduction in lesion area and macrophage infiltration around the lesion site (p < 0.0001). Importantly, neither immobilized IFN-γ nor PDGF-AA increased macrophage infiltration. Retrograde tracing demonstrates improved neuronal regeneration through the use of immobilized growth factors. Immunohistochemistry staining demonstrates that immobilized growth factors are effective in differentiating encapsulated cells into their anticipated lineages within the hydrogel, while qualitatively reducing glial fibrillary acid protein expression.

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

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    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.

  14. 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.

  15. Perfluorinated compounds in umbilical cord blood and adverse birth outcomes.

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    Mei-Huei Chen

    Full Text Available BACKGROUND: Previous animal studies have shown that perfluorinated compounds (PFCs have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA, perfluorooctyl sulfonate (PFOS, perfluorononanoic acid (PFNA, and perfluoroundecanoic acid (PFUA and birth outcomes. METHODS: In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS. Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The geometric mean (standard deviation levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23, 5.94 (1.95, 2.36(4.74, and 10.26 (3.07 ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted β (95% confidence interval, CI = -0.37 (-0.60, -0.13 wks, -110.2 (-176.0, -44.5 gm and -0.25 (-0.46, -0.05 cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR (95%CI = 2.45 (1.47, 4.08, 2.61(0.85, 8.03 and 2.27 (1.25, 4.15]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. CONCLUSIONS: An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs.

  16. Carbohydrate-mediated inhibition of ice recrystallization in cryopreserved human umbilical cord blood.

    Science.gov (United States)

    Wu, Luke K; Tokarew, Jacqueline M; Chaytor, Jennifer L; von Moos, Elizabeth; Li, Yuhua; Palii, Carmen; Ben, Robert N; Allan, David S

    2011-01-01

    Cryopreservation of human umbilical cord blood (UCB) typically involves the cryoprotectant dimethylsulfoxide (DMSO), however, infusional toxicity and reductions in cell viability remain a concern. Ice recrystallization (IR) is an important source of cryopreservation-induced cellular injury and limits the stem cell dose in UCB units. Carbohydrates have wide-ranging intrinsic IR inhibition (IRI) activity related to structural properties. We investigated the impact of carbohydrate IRI on cell viability, induction of apoptosis and hematopoietic progenitor function in cryopreserved UCB. Mononuclear cells (MNCs) from UCB were cryopreserved in storage media containing specific carbohydrates (200mM) and compared to 5% DMSO. Samples were analyzed under conditions of high IR ('slow' thaw) and low IR ('fast' thaw). Thawed samples were analyzed for viability and apoptosis by flow cytometry and hematopoietic function using colony-forming unit (CFU) assays. IRI of carbohydrate solutions was determined using the 'splat cooling' assay. Greater IRI capacity of carbohydrates correlated with increased yield of viable MNCs (r(2)=0.92, p=0.004) and CD34(+) cells (r(2)=0.96, p=0.019) after thawing under conditions of high IR. The correlations were less apparent under conditions of low IR. Carbohydrates with greater IRI modulate the induction of early apoptosis during thawing, especially in CD34+ cells (r(2)=0.96, p=0.0001) as compared to total mononuclear cells (p=0.006), and preserve CFU capacity in vitro (r(2)=0.92, p=<0.0001). Our results suggest that carbohydrates with potent IRI increase the yield of non-apoptotic and functional hematopoietic progenitors and provide a foundation for the development of novel synthetic carbohydrates with enhanced IRI properties to improve cryopreservation of UCB.

  17. Analysis of risk factors of cord blood transplantation for children.

    Science.gov (United States)

    Goldstein, Gal; Bielorai, Bella; Stein, Jerry; Stepensky, Polina; Elhasid, Ronit; Zaidman, Irena; Chetrit, Angela; Yaniv, Isaac; Nagler, Arnon; Toren, Amos

    2013-12-01

    As cord blood (CB) is being used frequently as a source for heamtopoetic stem cell transplantation defining risk factors for transplantation outcome is an important issue. The data of all single unit CB transplantation preformed in Israel from 1992 to 2011 were collected. The risk factors for myeloid engraftment, event free survival (EFS) and overall survival (OS) were studied in 87 children. There were 49 children with hematological malignancies and 38 with non-malignant diseases. Cumulative rate of neutrophil recovery was 78.3%, while median time to myeloid recovery was 26 days. The incidence of platelet engraftment at 150 days was 53%, and the median time to platelet recovery was 36 days. ABO blood group matching between CB unit and recipient was associated with superior myeloid engraftment. Acute graft versus host disease of grades II-IV occurred in 33% of the patients. Chronic graft versus host disease occurred in 16% of patients. Probabilities of EFS and OS at 1 year were 45% and 57%, respectively. Factors associated with inferior OS were Rh major mismatch versus matched Rh and transplantation from unrelated donor versus related donor. These results indicate that matching of ABO blood groups is an important factor that affects engraftment, and also that Rh matching seem to have an impact on OS, which was not previously described in the setting of CB transplantation. © 2013 Wiley Periodicals, Inc.

  18. Lead Level in Umbilical Cord Blood and its Effects on Newborns Anthropometry.

    Science.gov (United States)

    Neda, Akbari-Nassaji; Fahimeh, Sabeti; Tahereh, Ziaei Kajbaf; Leila, Fakharzadeh; Zahra, Nazari; Bahman, Cheraghian; Narges, Cham Kouri

    2017-06-01

    High concentration of blood lead is accompanied by adverse health effects on growth of foetus and the newborn. The aim of this study was to determine umbilical cord blood lead level and its relationship with birth weight, length and head circumference of the newborns in Abadan, Iran. In this cross-sectional study, 3 ml blood was collected from the umbilical cord vein in 147 newborns, immediately after the birth. Blood lead was measured using atomic absorption spectrophotometry. Data collection instruments included demographic questionnaire (age of mother, gestational age, newborn gender, job and education of mother) and also data registration form (umbilical cord blood lead concentration, weight, length, and head circumference of newborn). Data was analyzed with SPSS software version 16.0. The mean of umbilical cord blood lead was determined 0.65±0.32 µg/dl (0.3-1.35 µg/dl). The decrease of birth weight with increased blood lead level was small and was not statistically significant. There was reverse significant correlation between umbilical cord blood lead level and birth length and head circumference. There was no significant correlation between blood lead and other variables such as age, weight, education and job of mother and gestational age. Umbilical blood lead level was determined umbilical cord blood lead caused decreasing birth weight, length and head circumference of the newborns.

  19. Molecular mapping of the origin of postnatal spinal cord ependymal cells: evidence that adult ependymal cells are derived from Nkx6.1+ ventral neural progenitor cells.

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    Fu, Hui; Qi, Yingchuan; Tan, Min; Cai, Jun; Hu, Xuemei; Liu, Zijing; Jensen, Jan; Qiu, Mengsheng

    2003-02-10

    Recent studies have suggested that the ependymal cells lining the central canal of postnatal spinal cord possess certain properties of neural stem cells. However, the embryonic origin and developmental potential of the postnatal spinal cord ependymal cells remain to be defined. In this report, we investigated the developmental origin of postnatal spinal ependymal cells by studying the dynamic expression of several neural progenitor genes that are initially expressed in distinct domains of neuroepithelium in young embryos. At later stages of development, as the ventricular zone of the embryonic spinal cord is reduced, expression of Nkx6.1 progenitor gene is constantly detected in ependymal cells throughout chick and mouse development. Expression of other neural progenitor genes that lie either dorsal or ventral to the Nkx6.1+ domain is gradually decreased and eventually disappeared. These results suggest that the remaining neuroepithelial cells at later stages of animal life are derived from the Nkx6.1+ ventral neuroepithelial cells. Expression of Nkx6.1 in the remaining neuroepithelium is closely associated with, and regulated by, Shh expression in the floor plate. In addition, we suggested that the Nkx6.1+ ependymal cells in adult mouse spinal cords may retain the proliferative property of neural stem cells.

  20. Dexmedetomidine Attenuates Blood-Spinal Cord Barrier Disruption Induced by Spinal Cord Ischemia Reperfusion Injury in Rats

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    Bo Fang

    2015-05-01

    Full Text Available Background/Aims: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB disruption induced by spinal cord I/R injury. Methods: Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9, Angiopoietin-1 (Ang1 and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. Results: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. Conclusions: Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.

  1. Comparisons of polybrominated diphenyl ethers levels in paired South Korean cord blood, maternal blood, and breast milk samples.

    Science.gov (United States)

    Kim, Tae Hyung; Bang, Du Yeon; Lim, Hyun Jung; Won, A Jin; Ahn, Mee Young; Patra, Nabanita; Chung, Ki Kyung; Kwack, Seung Jun; Park, Kui Lea; Han, Soon Young; Choi, Wahn Soo; Han, Jung Yeol; Lee, Byung Mu; Oh, Jeong-Eun; Yoon, Jeong-Hyun; Lee, Jaewon; Kim, Hyung Sik

    2012-03-01

    Polybrominated diphenyl ethers (PBDEs), commonly used flame retardants, have been reported as potential endocrine disruptor and neurodevelopmental toxicants, thus giving rise to the public health concern. The goal of this study was to investigate the relationship between umbilical cord blood, maternal blood, and breast milk concentrations of PBDEs in South Korean. We assessed PBDE levels in paired samples of umbilical cord blood, maternal blood, and breast milk. The levels of seven PBDE congeners were measured in 21 paired samples collected from the Cheil Woman's Hospital (Seoul, Korea) in 2008. We also measured thyroid hormones levels in maternal and cord blood to assess the association between PBDEs exposure and thyroid hormone levels. However, there was no correlation between serum thyroxin (T4) and total PBDEs concentrations. The total PBDEs concentrations in the umbilical cord blood, maternal blood, and breast milk were 10.7±5.1 ng g(-1) lipid, 7.7±4.2 ng g(-1) lipid, and 3.0±1.8 ng g(-1) lipid, respectively. The ranges of total PBDE concentrations observed were 2.28-30.94 ng g(-1) lipid in umbilical cord blood, 1.8-17.66 ng g(-1) lipid in maternal blood, and 1.08-8.66 ng g(-1) lipid in breast milk. BDE-47 (45-73% of total PBDEs) was observed to be present dominantly in all samples, followed by BDE-153. A strong correlation was found for major BDE-congeners between breast milk and cord blood or maternal blood and cord blood samples. The measurement of PBDEs concentrations in maternal blood or breast milk may help to determine the concentration of PBDEs in infant.

  2. Maturation of blood vessels by haematopoietic stem cells and progenitor cells: involvement of apelin/APJ and angiopoietin/Tie2 interactions in vessel caliber size regulation.

    Science.gov (United States)

    Takakura, Nobuyuki; Kidoya, Hiroyasu

    2009-06-01

    Apelin is a recently-isolated bioactive peptide from bovine gastric extract. The gene encodes a protein of 77 amino acids, which can generate two active polypeptides, long (42-77) and short (65-77). Both peptides ligate and activate APJ, a G protein-coupled receptor expressed in the cardiovascular and central nervous systems. Although an essential role for the apelin/APJ system in blood vessel formation has been reported in Xenopus, its precise function in mammals is unclear. Blood vessel tube formation is accomplished by two main mechanisms: 1) single cell hollowing, in which a lumen forms within the cytoplasm of a single endothelial cell (EC), and 2) cord hollowing in which a luminal cavity is created de novo between ECs in a thin cylindrical cord. Molecular control of either single cell or cord hollowing has not been precisely determined. Angiopoietin-1 (Ang1) has been reported to induce enlargement of blood vessels. Apelin is produced from ECs upon activation of Tie2, a cognate receptor of Ang1, expressed on ECs. It has been suggested that apelin induces cord hollowing by promoting proliferation and aggregation/assembly of ECs. During angiogenesis, haematopoietic stem cells (HSCs) and progenitor cells (HPCs) are frequently observed in the perivascular region. They produce Ang1 and induce migration of ECs, resulting in a fine vascular network. Moreover, HSCs/HPCs can induce apelin production from ECs. Therefore, this review article posits that HSCs/HPCs regulate caliber size of blood vessels via apelin/APJ and Angiopoietin/Tie2 interactions.

  3. Ephrin-B3 decreases the survival of adult rat spinal cord-derived neural stem/progenitor cells in vitro and after transplantation into the injured rat spinal cord.

    Science.gov (United States)

    Fan, Xin Yan Susan; Mothe, Andrea J; Tator, Charles H

    2013-02-01

    Although transplantation of neural stem/progenitor cells (NSPC) encourages regeneration and repair after spinal cord injury (SCI), the survival of transplanted NSPC is limited. Ephrin-B3 has been shown to reduce the death of endogenous NSPC in the subventricular zone of the mouse brain without inducing uncontrolled proliferation. Due to similarities in the environment of the brain and spinal cord, we hypothesized that ephrin-B3 might reduce the death of both transplanted and endogenous spinal cord-derived NSPC. Both normal and injured (26 g clip compression) spinal cords were examined. Ephrin-B3-Fc was tested, and Fc fragments and phosphate-buffered saline (PBS) were used as controls. We found that EphA4 receptors were expressed by spinal cord-derived NSPC and expressed in the normal and injured rat spinal cord (higher expression in the latter). In vitro, ephrin-B3-Fc did not significantly reduce the survival of NSPC except at 1 μg/mL (Pinjured spinal cord compared with the infusion of PBS (Pinjured spinal cord, the infusion of either ephrin-B3-Fc or Fc fragments alone caused a 20-fold reduction in the survival of transplanted NSPC (P<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

  4. Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. 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.

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

    Science.gov (United States)

    Nishishita, Naoki; Takenaka, Chiemi; Fusaki, Noemi; Kawamata, Shin

    2011-01-01

    We report that iPS cells can be safely and effectively generated from fresh human cord blood (CB) cells with Sendai virus (SeV) vector carrying reprogramming factors OCT3/4, SOX2, KLF4, and c-MYC. The SeV vector is a single strand RNA virus having no DNA phase, and selectively infects the freshly isolated CD34+ CD45low+ fraction of CB cells corresponding to hematopoietic progenitors. Approximately twenty ES cell-like colonies emerged from 1 x 104 freshly isolated CD34+ CB cells around 18 days after SeV infection and were selected for passage to reduce the frequency of the remaining SeV-infected cells. The complete elimination of viral constructs was confirmed after several passages by immunostaining with monoclonal antibody against hemagglutinin-neuraminidase (HN) and by RT-PCR analysis. Five ES cell-like clones were selected to examine their in vitro potential for three germ layer differentiation and their capacity for teratoma formation. Generation of non-integrating Sendai virus (SeV) iPS cells from CB cells may be an important step to provide allogeneic iPS cell-derived therapy in the future.

  7. Age, Sex, and Religious Beliefs Impact the Attitude towards Cord Blood Banking.

    Science.gov (United States)

    Sundell, Inger Birgitta; Setzer, Teddi J

    2015-01-01

    In this study, a self-administered questionnaire was used to assess opinions about stem cell research and cord blood banking. Three attitudes were examined: willingness to accept cord blood banking, willingness to accept embryonic stem cell research, and religious belief system. A total of 90 Wayne State University students enrolled in the study in response to an invitation posted on a web page for the university. Sex distribution among study participants was 79 females and eight males; three declined to state their sex. Support for cord blood banking was high (> 70%) among students. Students over the age of 25 years of age were more (85%) positive than students 18 to 24 years old (57%). They prefered a public cord blood bank over a private cord blood bank. Atheist/agnostic or spiritual/not religious students (> 90%), Catholic students (78%) and Christian students (58%) support cord blood banking. Age, sex and religion seems influence the student's attitude towards stem cell research and cord blood banking.

  8. Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy.

    Science.gov (United States)

    Lei, Jun; Paules, Cristina; Nigrini, Elisabeth; Rosenzweig, Jason M; Bahabry, Rudhab; Farzin, Azadeh; Yang, Samuel; Northington, Frances J; Oros, Daniel; McKenney, Stephanie; Johnston, Michael V; Graham, Ernest M; Burd, Irina

    2017-01-01

    There are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood. This was a nested case-control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia ex vivo. NOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In ex vivo experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in ex vivo culture medium. This is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury.

  9. Nanofiber mat spinal cord dressing-released glutamate impairs blood-spinal cord barrier

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    Dorota Sulejczak

    2016-12-01

    Full Text Available An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB. This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an ‘empty’ (i.e., carrying no glutamate nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo­lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less

  10. Grafted human embryonic progenitors expressing neurogenin-2 stimulate axonal sprouting and improve motor recovery after severe spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Florence E Perrin

    Full Text Available BACKGROUND: Spinal cord injury (SCI is a widely spread pathology with currently no effective treatment for any symptom. Regenerative medicine through cell transplantation is a very attractive strategy and may be used in different non-exclusive ways to promote functional recovery. We investigated functional and structural outcomes after grafting human embryonic neural progenitors (hENPs in spinal cord-lesioned rats. METHODS AND PRINCIPAL FINDINGS: With the objective of translation to clinics we have chosen a paradigm of delayed grafting, i.e., one week after lesion, in a severe model of spinal cord compression in adult rats. hENPs were either naïve or engineered to express Neurogenin 2 (Ngn2. Moreover, we have compared integrating and non-integrating lentiviral vectors, since the latter present reduced risks of insertional mutagenesis. We show that transplantation of hENPs transduced to express Ngn2 fully restore weight support and improve functional motor recovery after severe spinal cord compression at thoracic level. This was correlated with partial restoration of serotonin innervations at lumbar level, and translocation of 5HT1A receptors to the plasma membrane of motoneurons. Since hENPs were not detectable 4 weeks after grafting, transitory expression of Ngn2 appears sufficient to achieve motor recovery and to permit axonal regeneration. Importantly, we also demonstrate that transplantation of naïve hENPs is detrimental to functional recovery. CONCLUSIONS AND SIGNIFICANCE: Transplantation and short-term survival of Ngn2-expressing hENPs restore weight support after SCI and partially restore serotonin fibers density and 5HT1A receptor pattern caudal to the lesion. Moreover, grafting of naïve-hENPs was found to worsen the outcome versus injured only animals, thus pointing to the possible detrimental effect of stem cell-based therapy per se in SCI. This is of major importance given the increasing number of clinical trials involving cell

  11. Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation.

    OpenAIRE

    Salmon, Jean; Michaux, S.; Hermanne, J. P.; Baudoux, Etienne; Gerard, Christiane; Sondag, Danièle; Fillet, Georges; Beguin, Yves

    1999-01-01

    BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor-derived ABO antibodies. This reaction may be more severe after transplantation of peripheral blood progenitor cells (PBPCs). CASE REPORT: A 16-year-old boy underwent an allogeneic PBPC transplant from his HLA-mismatched mother as treatment for acute myeloblastic leukemia that had proved resistant to induction chemotherapy. Transfusion of th...

  12. Effect of hemoglobin adjustment on the precision of mercury concentrations in maternal and cord blood

    DEFF Research Database (Denmark)

    Kim, Byung-Mi; Choi, Anna L; Ha, Eun-Hee

    2014-01-01

    and structural equation model (SEM) analyses were used to ascertain interrelationships between the exposure biomarkers and the possible impact of hemoglobin as well as selenium. Both methods showed a significant dependence of the cord-blood concentration on hemoglobin, also after adjustment for other exposure...... biomarkers. In the SEM, the cord blood measurement was a less imprecise indicator of the latent methylmercury exposure variable than other exposure biomarkers available, and the maternal hair concentration had the largest imprecision. Adjustment of mercury concentrations both in maternal and cord blood...

  13. Umbilical cord blood lactate: a valuable tool in the assessment of fetal metabolic acidosis

    DEFF Research Database (Denmark)

    Gjerris, A.C.; Staer-Jensen, J.; Jorgensen, J.S.

    2008-01-01

    OBJECTIVE: The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and pH, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal...... asphyxia using ROC-curves, where an ABE value less than -12 was used as "gold standard" for significant intrapartum asphyxia. STUDY DESIGN: This is a descriptive study of umbilical cord arterial blood samples from 2554 singleton deliveries. The deliveries took place at the Department of Obstetrics...... and Gynaecology, Hvidovre University Hospital, Copenhagen, Denmark where umbilical cord blood sampling and blood gas analysis is part of the routine assessment of all newborns. RESULTS: We found significant correlations between lactate and pH (r=-0.73), lactate and SBE (r=-0.76), and lactate and ABE (r=-0...

  14. Umbilical Cord Blood Use for Admission Blood Tests of VLBW (Very Low Birth Weight) Preterm Neonates: A Multi-center Randomized Clinical Trial

    Science.gov (United States)

    2016-09-12

    collection of information if it does not display a currently valid OMB control number. Umbilical Cord Blood Use for Admission Blood Tests of VLBW Preterm...to help decrease the risk of anemia and the need for transfusion. These include delayed cord clamping , cord stripping, erythropoiesis stimulating...transcutaneous measurements[3, 6]. Another approach used to decrease the risk of anemia and need for transfusion is the use of umbilical cord blood

  15. Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.

    Directory of Open Access Journals (Sweden)

    Ilaria Burba

    Full Text Available BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs, have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+ were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+ cells with enhanced self renewal and cardioprotection.

  16. Effect of Prenatal Selenium Supplementation on Cord Blood Selenium and Lipid Profile

    Directory of Open Access Journals (Sweden)

    Hassan Boskabadi

    2012-12-01

    Conclusion: Our findings suggest that selenium supplementation in pregnant women may be associated with an increased cord-blood triglyceride level, although total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol levels did not change significantly. The clinical significance of the increased cord triglyceride concentration needs to be evaluated.

  17. Generation of induced pluripotent stem cells from human cord blood cells with only two factors: Oct4 and Sox2.

    Science.gov (United States)

    Giorgetti, Alessandra; Montserrat, Nuria; Rodriguez-Piza, Ignacio; Azqueta, Carmen; Veiga, Anna; Izpisúa Belmonte, Juan Carlos

    2010-04-01

    Induced pluripotent stem cells (iPSC) provide an invaluable resource for regenerative medicine as they allow the generation of patient-specific progenitors with potential value for cell therapy. However, in many instances, an off-the-shelf approach is desirable, such as for cell therapy of acute conditions or when the patient's somatic cells are altered as a consequence of a chronic disease or aging. Cord blood (CB) stem cells appear ideally suited for this purpose as they are young cells expected to carry minimal somatic mutations and possess the immunological immaturity of newborn cells; additionally, several hundred thousand immunotyped CB units are readily available through a worldwide network of CB banks. Here we present a detailed protocol for the derivation of CB stem cells and how they can be reprogrammed to pluripotency by retroviral transduction with only two factors (OCT4 and SOX2) in 2 weeks and without the need for additional chemical compounds.

  18. Silencing BRE expression in human umbilical cord perivascular (HUCPV progenitor cells accelerates osteogenic and chondrogenic differentiation.

    Directory of Open Access Journals (Sweden)

    Elve Chen

    Full Text Available BRE is a multifunctional adapter protein involved in DNA repair, cell survival and stress response. To date, most studies of this protein have been focused in the tumor model. The role of BRE in stem cell biology has never been investigated. Therefore, we have used HUCPV progenitor cells to elucidate the function of BRE. HUCPV cells are multipotent fetal progenitor cells which possess the ability to differentiate into a multitude of mesenchymal cell lineages when chemically induced and can be more easily amplified in culture. In this study, we have established that BRE expression was normally expressed in HUCPV cells but become down-regulated when the cells were induced to differentiate. In addition, silencing BRE expression, using BRE-siRNAs, in HUCPV cells could accelerate induced chondrogenic and osteogenic differentiation. Hence, we postulated that BRE played an important role in maintaining the stemness of HUCPV cells. We used microarray analysis to examine the transcriptome of BRE-silenced cells. BRE-silencing negatively regulated OCT4, FGF5 and FOXO1A. BRE-silencing also altered the expression of epigenetic genes and components of the TGF-β/BMP and FGF signaling pathways which are crucially involved in maintaining stem cell self-renewal. Comparative proteomic profiling also revealed that BRE-silencing resulted in decreased expressions of actin-binding proteins. In sum, we propose that BRE acts like an adaptor protein that promotes stemness and at the same time inhibits the differentiation of HUCPV cells.

  19. Umbilical cord blood acid-base and gas analysis after early versus delayed cord clamping in neonates at term.

    Science.gov (United States)

    De Paco, Catalina; Florido, Jesús; Garrido, Mari Carmen; Prados, Sonia; Navarrete, Luis

    2011-05-01

    To compare umbilical cord acid-base status and blood gas analysis between umbilical cords clamped within 10 s and at 2 min of delivery. A total of 158 healthy full-term mothers were randomly assigned to an early clamping (clamping (2 min post-delivery, n = 79) group. After application of inclusion criteria, umbilical vein blood acid-base status and gases were analyzed in 65 early clamped and 51 delayed clamped cords. Fewer cases could be examined in the umbilical artery: 55 cords in the early clamping group and 44 in the delayed one. Acid-base and gas analysis results did not significantly differ between the groups in the umbilical vein or umbilical artery, with the exception of a higher (p umbilical artery pO(2) value in the delayed versus early clamping group. No significant differences in umbilical vein or artery pCO(2) or HCO(3) (-) values were observed between the early and delayed clamp groups. A delay of 2 min before umbilical cord clamping does not significantly change acid-base and gas analysis results, with the exception of a higher mean umbilical artery pO(2) value in the delayed clamping group.

  20. Evaluating perfusion of thoracic spinal cord blood using CEUS during thoracic spinal stenosis decompression surgery.

    Science.gov (United States)

    Ling, J; Jinrui, W; Ligang, C; Wen, C; Xiaoguang, L; Liang, J

    2015-01-13

    Study design:A clinical study in human spinal cord.Objectives:To evaluate changes in spinal cord blood perfusion in patients with thoracic spinal stenosis using contrast-enhanced ultrasonography and to semiquantitatively analyze blood perfusion changes in compressed spinal cord before and after ventral decompression.Setting:Ultrasound department of a university hospital.Methods:Twelve patients with confirmed thoracic spinal stenosis who needed decompression surgery participated. They underwent an intravenous injection of a contrast agent before and after ventral decompression. Quantitative analysis software (Philips Healthcare, Bothell, WA, USA) was used to perform time-intensity curve (TIC) analysis. The enhanced intensity (ΔI), rise time (ΔT) and slope of the TIC (β) were separately calculated; t-tests of the independent samples were performed on the indicators.Results:The TICs showed no significant differences between compressed spinal cord and normal spinal cord in ΔT, enhanced ΔI and β (P= 0.46, P=0.23 and P=0.16, respectively). After ventral decompression, ΔI of the originally compressed spinal cord increased substantially (P= 0.04) compared with ΔI of the normal spinal cord; however, the ΔT and β showed no significant differences (P= 0.18 and P=0.09, respectively). Comparison of the blood perfusion parameters (that is, ΔT and ΔI) of the compressed spinal cords before and after ventral decompression showed no significant differences (P=0.14 and P=0.12, respectively), but β showed significant difference (P=0.02).Conclusion:Contrast-enhanced ultrasonography can dynamically display spinal cord blood perfusion. The characteristics of blood perfusion can be semiquantitatively analyzed using a software technique.Spinal Cord advance online publication, 13 January 2015; doi:10.1038/sc.2014.213.

  1. Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective.

    Science.gov (United States)

    Beak, Carla Pereira; Chargé, Sophie B; Isasi, Rosario; Knoppers, Bartha M

    2015-05-01

    In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS-in collaboration with researchers from the Stem Cell Network-have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.

  2. Association of food consumption during pregnancy with mercury and lead levels in cord blood.

    Science.gov (United States)

    Kim, Jin Hee; Lee, Su Jin; Kim, Su Young; Choi, Gyuyeon; Lee, Jeong Jae; Kim, Hai-Joong; Kim, Sungjoo; Park, Jeongim; Moon, Hyo-Bang; Choi, Kyungho; Kim, Sungkyoon; Choi, Soo Ran

    2016-09-01

    In utero exposure to mercury and lead has been linked to various adverse health effects related to growth and development. However, there was no evidence on the relationship between food consumption during pregnancy and mercury or lead level in cord blood. Therefore we measured mercury and lead levels in bloods, urines, and cord bloods obtained from 302 pregnant women and estimated relationships between food consumption during pregnancy and mercury or lead level in cord blood to identify perinatal mercury and lead exposures originated from foods during pregnancy. Relationship between food consumption and mercury or lead level was estimated using a generalized linear model after adjustment for body mass index (BMI), delivery experience, income, recruitment year, and other dietary factors for mercury and age, BMI, cesarean section, delivery experience, recruitment year, and other dietary factors for lead. Fish consumption was positively associated with mercury level in cord blood (p=0.0135), while cereal and vegetable consumptions were positively associated with lead level in cord blood (p=0.0517 for cereal and p=0.0504 for vegetable). Furthermore, tea consumption restrained increase of lead level in cord blood (p=0.0014). Our findings support that mercury or lead exposure in Korean pregnant women may come from frequent fish and cereal or vegetable consumption while tea consumption may decrease lead exposure in pregnant women. Therefore, careful intervention through food consumption should be considered.

  3. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  4. Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim

    2008-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) hospitalization is associated with wheeze. OBJECTIVE: To examine the influence of maternally derived RSV neutralizing antibodies in cord blood on RSV hospitalization and recurrent wheeze in infancy. METHODS: Among children from the Danish National Bir...

  5. Total and antigen-specific Ige levels in umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Sybilski AJ

    2009-12-01

    Full Text Available Abstract The present study was conducted to learn whether the perinatal and environmental factors could influence the total and antigen-specific IgE levels in umbilical cord blood. Retrospective data were obtained from 173 mother-infant pairs. Total and specific (for children's food, wheat/grass and house dust mite-HDM cord blood IgE levels were determined using the immunoassay test. The total cord blood IgE was between 0.0-23.08 IU/ml (mean 0.55 ± 2.07 IU/ml; median 0.16 IU/ml. Total IgE levels were significantly higher in boys compared with girls (OR = 2.2; P = 0.007, and in newborns with complicated pregnancy (OR = 2.7; P = 0.003. A greater number of siblings correlated with increases in the total cord blood IgE (P

  6. Human astrocytes derived from glial restricted progenitors support regeneration of the injured spinal cord.

    Science.gov (United States)

    Haas, Christopher; Fischer, Itzhak

    2013-06-15

    Cellular transplantation using neural stem cells and progenitors is a promising therapeutic strategy that has the potential to replace lost cells, modulate the injury environment, and create a permissive environment for the regeneration of injured host axons. Our research has focused on the use of human glial restricted progenitors (hGRP) and derived astrocytes. In the current study, we examined the morphological and phenotypic properties of hGRP prepared from the fetal central nervous system by clinically-approved protocols, compared with astrocytes derived from hGRP prepared by treatment with ciliary neurotrophic factor or bone morphogenetic protein 4. These differentiation protocols generated astrocytes that showed morphological differences and could be classified along an immature to mature spectrum, respectively. Despite these differences, the cells retained morphological and phenotypic plasticity upon a challenge with an alternate differentiation protocol. Importantly, when hGRP and derived astrocytes were transplanted acutely into a cervical dorsal column lesion, they survived and promoted regeneration of long ascending host sensory axons into the graft/lesion site, with no differences among the groups. Further, hGRP taken directly from frozen stocks behaved similarly and also supported regeneration of host axons into the lesion. Our results underscore the dynamic and permissive properties of human fetal astrocytes to promote axonal regeneration. They also suggest that a time-consuming process of pre-differentiation may not be necessary for therapeutic efficacy, and that the banking of large quantities of readily available hGRP can be an appropriate source of permissive cells for transplantation.

  7. Ethical and legal issues raised by cord blood banking - the challenges of the new bioeconomy.

    Science.gov (United States)

    Stewart, Cameron L; Aparicio, Lorena C; Kerridge, Ian H

    2013-08-19

    Cord blood banking raises ethical and legal issues which highlight the need for careful regulatory approaches to the emerging bioeconomy. • Consent processes for both private and public banking should be inclusive and representative of the different familial interests in the cord blood. • Property law is a potentially useful way of understanding the mechanisms for donation to both public and private banks. • Increasing tensions between public and private models of banking may require the adoption of hybrid forms of banking.

  8. Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development

    Directory of Open Access Journals (Sweden)

    Christian Hellmuth

    2017-04-01

    Full Text Available Background/Aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA, polar lipids, non-esterified fatty acids (NEFA, and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.

  9. Relation between Cord Blood Mercury Levels and Early Child Development in a World Trade Center Cohort

    OpenAIRE

    Lederman, Sally Ann; Jones, Robert L.; Caldwell, Kathleen L.; Rauh, Virginia; Sheets, Stephen E.; Tang, Deliang; Viswanathan, Sheila; Becker, Mark; Stein, Janet L.; Wang, Richard Y; Perera, Frederica P.

    2008-01-01

    Objective This study was designed to determine whether prenatal mercury exposure, including potential releases from the World Trade Center (WTC) disaster, adversely affects fetal growth and child development. Methods We determined maternal and umbilical cord blood total mercury of nonsmoking women who delivered at term in lower Manhattan after 11 September 2001, and measured birth outcomes and child development. Results Levels of total mercury in cord and maternal blood were not significantly...

  10. Prevalence of Medical Conditions Potentially Amenable to Cellular Therapy among Families Privately Storing Umbilical Cord Blood.

    Science.gov (United States)

    Mazonson, Peter; Kane, Mark; Colberg, Kelin; Harris, Heather; Brown, Heather; Mohr, Andrew; Ziman, Alyssa; Santas, Chris

    2017-01-01

    Introduction Little is known about the prevalence of conditions potentially amenable to cellular therapy among families storing umbilical cord blood in private cord blood banks. Methods A cross-sectional study of families with at least one child who stored umbilical cord blood in the largest private cord blood bank in the United States was performed. Respondent families completed a questionnaire to determine whether children with stored cord blood or a first-degree relative had one or more of 16 conditions amenable primarily to allogeneic stem cell transplant ("transplant indications") or 16 conditions under investigation for autologous stem cell infusion ("regenerative indications"), regardless of whether they received a transplant or infusion. Results 94,803 families responded, representing 33.3 % of those surveyed. Of respondent families, 16.01 % indicated at least one specified condition. 1.64 % reported at least one first-degree member with a transplant indication potentially treatable with an allogeneic stem cell transplant. The most common transplant indications reported among first-degree family members were Non-Hodgkin's Lymphoma (0.33 %), Hodgkin's Lymphoma (0.30 %), and Acute Lymphoblastic Leukemia (0.28 %). 4.23 % reported at least one child with a regenerative indication potentially treatable with an autologous stem cell infusion. The most common regenerative indications among children with stored umbilical cord blood were Autism/Autism Spectrum Disorder/Apraxia (1.93 %), Other Developmental Delay (1.36 %), and Congenital Heart Defect (0.87 %). Discussion Among families storing umbilical cord blood in private cord blood banks, conditions for which stem cell transplant or infusion may be indicated, or are under investigation, appear to be prevalent, especially for regenerative medicine indications.

  11. Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

    Science.gov (United States)

    Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2017-08-01

    To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

  12. In vitro susceptibilities in lymphocytes from mothers and cord blood to the monofunctional alkylating agent EMS

    DEFF Research Database (Denmark)

    Wyatt, N P; Falque-Gonzalez, C; Farrar, D;

    2007-01-01

    at the Bradford Royal Infirmary collected venous blood samples from mothers at the time of birth and venous cord blood post-delivery. Lymphocytes were isolated from both blood types and examined in the alkaline comet assay using the monofunctional alkylating agent ethyl methanesulphonate (EMS). There were...

  13. Concentration of Lead, Mercury, Cadmium, Aluminum, Arsenic and Manganese in Umbilical Cord Blood of Jamaican Newborns

    Directory of Open Access Journals (Sweden)

    Mohammad H. Rahbar

    2015-04-01

    Full Text Available The objective of this study was to characterize the concentrations of lead, mercury, cadmium, aluminum, and manganese in umbilical cord blood of Jamaican newborns and to explore the possible association between concentrations of these elements and certain birth outcomes. Based on data from 100 pregnant mothers and their 100 newborns who were enrolled from Jamaica in 2011, the arithmetic mean (standard deviation concentrations of cord blood lead, mercury, aluminum, and manganese were 0.8 (1.3 μg/dL, 4.4 (2.4 μg/L, 10.9 (9.2 μg/L, and 43.7 (17.7 μg/L, respectively. In univariable General Linear Models, the geometric mean cord blood aluminum concentration was higher for children whose mothers had completed their education up to high school compared to those whose mothers had any education beyond high school (12.2 μg/L vs. 6.4 μg/L; p < 0.01. After controlling for maternal education level and socio-economic status (through ownership of a family car, the cord blood lead concentration was significantly associated with head circumference (adjusted p < 0.01. Our results not only provide levels of arsenic and the aforementioned metals in cord blood that could serve as a reference for the Jamaican population, but also replicate previously reported significant associations between cord blood lead concentrations and head circumference at birth in other populations.

  14. IN VITRO STUDY ON THE CLONING AND TRANSDUCTION OF HUMAN O6-METHYLGUANINE-DNA-METHYLTRANSFERASE CDNA INTO HUMAN UMBILICAL CORD BLOOD CD34+ CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore whether human umbilical cord blood hematopoietic progenitor cells transduced with human O6-methylguanine-DNA-methyltransferase (MGMT) gene could increase resistance to 1,3-Bis(2-Chloroethyl)-1-Nitrosourea (BCNU). Methods: The cDNA encoding the MGMT was isolated by using RT-PCR method from total RNA of fresh human liver, the fragment was cloned into pGEM-T vector and further subcloned into G1Na retrovirus vector. Then the G1Na-MGMT was transduced into the packaging cell lines GP+E86 and PA317 by LipofectAMINE. By using the medium containing BCNU for cloning selection and ping-ponging supernatant infection between ecotropic producer clone and amphotropic producer clone, high titer amphotropic PA317 producer clone with the highest titer up to 5.8′ 105 CFU/ml was obtained. Cord blood CD34+ cells were transfected repeatedly with supernatant of retrovirus containing human MGMT-cDNA under stimulation of hemopoietic growth factors. Results: The retrovirus vector construction was verified by restriction endonuclease analysis and DNA sequencing. PCR, RT-PCR, Southern Blot, Western Blot and MTT analyses showed that MGMT drug resistance gene has been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The transgene cord blood CD34+ cells conferred 4-folds stronger resistance to BCNU than untransduced cells. Conclusion: The retrovirus vector-mediated transfer of MGMT drug resistance gene into human cord blood CD34+ cells and its expression provided an experimental foundation for gene therapy in clinical trial.

  15. Pre-birth selection of umbilical cord blood donors

    Science.gov (United States)

    Urciuoli, Patrizia; Passeri, Simona; Ceccarelli, Francesca; Luchetti, Barbara; Paolicchi, Aldo; Lapi, Simone; Nocchi, Francesca; Lamanna, Roberta; Iorio, Mariacarla; Vanacore, Renato; Mazzoni, Alessandro; Scatena, Fabrizio

    2010-01-01

    Background . The fact that only a small percentage of cord blood units (CBU) stored are actually used for transplantation contributes to raising the already high costs of their processing and cryopreservation. The identification of predictors allowing the early identification of suitable CBU would allow a reduction of costs for the collection, storage and characterisation of CBU with insufficient volume or cell numbers. In our bank we have adopted a cut-off value for using CBU of 8 × 108 nucleated cells and a volume ≥ 60 mL. Materials and methods In 365 banked CBU, we evaluated the correlation between neonatal/gestational parameters and laboratory data used to assess their quality. Results Biparietal diameter (BPD) and abdominal circumference were significantly and positively correlated with CBU volume (r2=0.12, p=0.0011 and r2=0.092, p=0.0063, respectively). Receiver operating characteristic (ROC) analysis showed that both parameters can be used to identify CBU with insufficient volume (BPD: area under the curve 0.69, 95% CI=0.57–0.82, p=0.004; abdominal circumference: area under the curve 0.67, 95% CI=0.54–0.79, p<0.01). BPD and head circumference, but not abdominal circumference or femoral length, were positively correlated with white blood cell (WBC) count (r2=0.215, p=0.031, and r2=0.299, p=0.015, respectively). Abdominal circumference, but not BPD, head circumference or femoral length, was statistically significantly correlated with the number of CD34+ cells in the CBU. Weight at birth and placental weight were positively correlated with WBC count, blood volume, CD34+ cell count, total colony-forming units and burst-forming units. Conclusion . Pre-birth assessment of BPD might allow the selection of donors who would yield CBU of sufficient volume and WBC count and avoid the costs of collecting, transferring, storing and analysing CBU with a high probability of resulting unsuitable for transplantation. PMID:20104277

  16. Occurrences of major polybrominated diphenyl ethers (PBDEs) in maternal and fetal cord blood sera in Korea.

    Science.gov (United States)

    Choi, Gyuyeon; Kim, Sungjoo; Kim, Sunmi; Kim, Sungkyoon; Choi, Youngeun; Kim, Hai-Joong; Lee, Jeong Jae; Kim, Su Young; Lee, Sunggyu; Moon, Hyo-Bang; Choi, Sooran; Choi, Kyungho; Park, Jeongim

    2014-09-01

    Polybrominated diphenyl ethers (PBDEs) are of growing public health concern because of their potential toxicities which range from endocrine disruption to neurodevelopment. However, information on their exposure among sensitive human populations is limited. The objectives of this study were to determine the levels of major PBDEs in blood sera of pregnant women and their matching newborn infants. For this purpose, a total of 198 maternal blood samples and 118 matching umbilical cord blood samples were collected from four regions of South Korea in 2011, and were determined for 19 PBDE congeners. Various demographic, dietary, and behavioral characteristics were asked in a questionnaire survey. Average concentration of total PBDEs in maternal blood serum was 3.34 ± 8.42 ng/g lipid weight (lw) at delivery and 3.14 ± 7.46 ng/g lw at 6 months of pregnancy, respectively. In cord blood serum, an average of 9.37 ± 12.60 ng/g lw was detected. Among the measured PBDE congeners, BDE-47, BDE-99 and BDE-153 were most dominant in both maternal and cord blood sera. Relatively higher levels of BDE-99 were detected in cord blood serum. Strong positive correlations were detected between maternal and cord blood serum samples, indicating the importance of maternal transfer. Health consequences of transplacental exposure to PBDEs among fetuses and newborn infants warrant further investigation.

  17. Expression of CXCR4 in cord blood-derived CD133+ cells treated with platelet micro-particles.

    Science.gov (United States)

    Moghaddam, Farzaneh; Oodi, Arezoo; Nikougoftar Zarif, Mahin; Amani, Maryam; Amirizadeh, Naser

    2016-11-01

    Platelet micro-particles (MPs) contain CXCR4 markers and are able to transfer them into hematopoietic stem cells. Therefore, effect of platelet MPs (PMPs) on the expression levels of CXCR4 and CD34 markers in these cells was examined. Isolated CD 133+ cells cultivated for 5 d in the stem span medium and PMPs. Fold increase of CD34+ cells in the presence of 5 and 10 g/ml of PMPs was increased significantly. CXCR4+ cell percent in the presence of 10 g/ml PMPs compared with control cells (63.8 ± 6.4) was increased (P < 0.05). PMPs were no affect on clonogenicity of hematopoietic progenitor cells. Cord blood CD133+ cells are able to maintain long-term hematopoiesis and to differentiate to hematopoietic lineages. CXCR4 over expression is involved in homing and successful transplantation of hematopoietic stem cells (HSCs) in the bone marrow. PMPs contain CXCR4 markers and are able to transfer them into hematopoietic stem cells. Therefore, considering the importance of CD133+ cells as primitive HSCs, the effect of PMPs on the expression levels of CXCR4 and CD34 markers in these cells was examined. Cord blood CD133+ cells were isolated by MACS. Isolated cells were divided into three groups: (i) control cells, (ii) cells treated with 5 μg/ml PMPs, (iii) cells treated with 10 μg/ml PMPs. Cells were cultivated for 5 d in the stem span medium. Expression of CD 133, CD34, and CXCR4 surface marker was analyzed by flow cytometry. Total cell numbers were counted by hemocytometer and clonogenicity were measured by colony assay. PMPs were no effect on CD133+ cells proliferation, but fold increase of CD34+ cells in the presence of 5 and 10 g/ml of PMPs was increased significantly. CXCR4+ cell percent in the presence of 10 g/ml PMPs compared with control cells (63.8 ± 6.4) was increased (P < 0.05). PMPs were no affect on clonogenicity of hematopoietic progenitor cells. Exposure of CD133+ cells isolated from cord blood to PMPs with 10

  18. Potential use of cord blood for Hb E hemoglobinopathy screening programme using capillary electrophoresis.

    Science.gov (United States)

    Wan Mohd Saman, W A; Hassan, R; Mohd Yusoff, S; Che Yaakob, C A; Abdullah, N A F; Ghazali, S; Mohd Radzi, M A R; Bahar, R

    2016-12-01

    Thalassemia and hemoglobinopathies are inherited red blood cell disorders found worldwide. Hemoglobin (Hb) E disorder is one of the hemoglobinopathies known to have the high prevalence in South East Asia. Most of transfusion-dependent thalassemias were genotypically compound heterozygous Hb E/ β-thalassemia. In Malaysia, the national screening program for thalassemia was implemented for early pregnancy or secondary school girls; however many participants do not turn-up and missed the screening test. Screening for thalassemia using samples from cord blood is an alternative choice as it is a readily available source of blood and hence early detection of the disease. The purpose of this study was to determine the potential use of cord blood for the screening of HbE hemoglobinopathy by using capillary electrophoresis (CE). Cord blood samples were collected from 300 newborns of healthy mothers. Hematological parameters were determined and hemoglobin quantitation for all cord blood samples were performed using capillary electrophoresis system (CES) and high performance liquid chromatography (HPLC). Majority of cord blood samples (63%) revealed Hb AF followed by Hb AFA2 (20%). Hb AFE was detected in 10.7% with the mean value of Hb E ranging from 2.3%-11.1%. Hemoglobin E was detected in cord blood using capillary electrophoresis system. It can be recommended in areas where Hb E/β is prevalent. Implementation of a screening strategy using CE on cord blood sampling will identify the disease early. With regular follow-up on these patients, the status of their disease can be determined earlier and appropriate management implemented.

  19. Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units

    Directory of Open Access Journals (Sweden)

    Stephen J. Proctor

    2010-01-01

    , supported by six mismatched cord blood units (one unit per 10 kg recipient weight. No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70 kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord.

  20. Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy.

    Science.gov (United States)

    Charrier, Emily; Cordeiro, Paulo; Brito, Rose-Marie; Harnois, Michaël; Mezziani, Samira; Herblot, Sabine; Le Deist, Françoise; Duval, Michel

    2014-10-01

    Plasmacytoid dendritic cells (pDCs) initiate both innate and adaptive immune responses, making them attractive targets for post-transplantation immunotherapy, particularly after cord blood transplantation (CBT). Toll-like receptor (TLR) agonists are currently studied for pDC stimulation in various clinical settings. Their efficacy depends on pDC number and functionality, which are unknown after CBT. We performed a longitudinal study of pDC reconstitution in children who underwent bone marrow transplantation (BMT) and single-unit CBT. Both CBT and unrelated BMT patients received antithymocyte globulin as part of their graft-versus-host disease prophylaxis regimen. pDC blood counts were higher in CBT patients than in healthy volunteers from 2 to 9 months after transplantation, whereas they remained lower in BMT patients. We showed that cord blood progenitors gave rise in vitro to a 500-fold increase in functional pDCs over bone marrow counterparts. Upon stimulation with a TLR agonist, pDCs from both CBT and BMT recipients upregulated T cell costimulatory molecules, whereas interferon-alpha (IFN-α) production was impaired for 9 months after CBT. TLR agonist treatment is thus not expected to induce IFN-α production by pDCs after CBT, limiting its immunotherapeutic potential. Fortunately, in vitro production of large amounts of functional pDCs from cord blood progenitors paves the way for the post-transplantation adoptive transfer of pDCs. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Relationship between leptin levels in maternal blood,amniotic fluid,arterial and venous cord blood and fetal growth

    Institute of Scientific and Technical Information of China (English)

    林丽莎; 薛昭卿; 宋岩峰; 何晓宇

    2003-01-01

    Objective:To study the relationship between leptin concentration and fetal growth.Methods: Levels of leptin in maternal serum, amniotic fluid, arterial and venouscord blood of 65 normal parturients (gestational age 37-42weeks) were measured by ra-dioimmunoassay (RIA) method. At the same time, maternal blood lipids were detected.Neonates were divided into three groups: small for gestational age (SGA) group (n=10), appropriate for gestational age (AGA) group (n=45), large for gestational age(LGA) group (n= 10). Statistical analysis was performed by t test, variance analysisand correlation analysis.Results: (1) There was no obvious correlation between leptin concentrations in ma-ternal serum and arterial/ venous cord blood, amniotic fluid, and also no correlationwith birth weight and placental weight (P>0.05). Maternal body mass index signifi-cantly correlated with birth weight and neonatal length and leptin levels in arterial andvenous cord blood (P<0.01). Leptin levels in arterial and venous cord blood positivelycorrelated significantly with placental and neonatal weight and body length (P<0.01)and negatively correlated with high density lipoprotein (P<0. 01). There was no obvi-ous correlation between fetal gender and leptin concentrations in maternal serum, arteri-al and venous cord blood and amniotic fluid; (2) Leptin levels in arterial and venouscord blood , placental weight in LGA group were significantly higher than those in SGAand AGA group (P<0.05). Among three groups, leptin concentrations in maternalblood were significantly higher than those in arterial and venous cord blood (P<0.05).Conclusions: (1)Fetal leptin is synthesized in uterus, born of itself and placenta.Leptin levels in arterial and venous cord blood are related to the intrauterine growthpattern. It might positively regulate birth weight and body fat content. (2)Either mater-nal or fetal leptin was not correlated with fetal gender. There is no gender difference infetal leptin

  2. Mobilization of human hematopoietic stem/progenitor-enriched CD34+ cells into peripheral blood during stress related to ischemic stroke.

    Directory of Open Access Journals (Sweden)

    M Z Ratajczak

    2006-06-01

    Full Text Available The bone marrow-derived stem/progenitor cells were demonstrated to play an important role in a regeneration of damaged tissue. Based on these observations we asked whether the stroke-related stress triggers mobilization of stem/progenitor cells from the bone marrow into the peripheral blood, which subsequently could contribute to regeneration of damaged organs. To address this issue, the peripheral blood samples were harvested from patients with ischemic stroke during the first 24 hrs as well as after the 48 (2nd day and 144 hrs (6th day since the manifestation of symptoms. In these patients we evaluated the percentage of hematopoietic stem/progenitor-enriched CD34+ cells by employing flow cytometry and the number of hematopoietic progenitor cells for the granulocyto-monocytic (CFU-GM and erythroid (BFU-E-lineages circulating in peripheral blood. We concluded that stress related to ischemic stroke triggers the mobilization of hematopoietic stem/progenitor cells from the bone marrow into peripheral blood. These circulating stem/progenitor cells may play an important role in the process of regeneration of the ischemic tissue.

  3. A neutralizing anti-TGF-beta1 antibody promotes proliferation of CD34+Thy-1+ peripheral blood progenitors and increases the number of transduced progenitors.

    Science.gov (United States)

    Imbert, A M; Bagnis, C; Galindo, R; Chabannon, C; Mannoni, P

    1998-05-01

    The subset of blood cells that expresses both CD34 and Thy1 (CD90) cell surface molecules is enriched in hematopoietic stem cell activity and can be obtained from the peripheral blood of cancer patients after mobilization by chemotherapy and granulocyte colony-stimulating factor (G-CSF). Because transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of hematopoietic progenitor proliferation and differentiation, in this study we analyzed the impact of neutralizing TGF-beta1 activity during culture and retroviral transduction of CD34+Thy1+ cells. When purified CD34+Thy1+ cells were cultured in the presence of a neutralizing antibody against TGF-beta1, the percentage of cycling cells, proliferation, and absolute number of clonogenic progenitors were increased in comparison to the cultures performed without the addition of antibody. Antibody-mediated neutralization of TGF-beta1 during retroviral transduction performed by coculture of CD34+Thy1+ cells with a MFG-S-nlsLacZ retroviral vector-producing cell line did not affect the percentage of transduced progenitors as assessed by direct X-Gal staining of colonies in clonogenic assays. However, due to the better expansion of CD34+Thy1+ cells in the presence of anti-TGF-beta1, the absolute number of transduced progenitors recovered at the end of the culture was increased.

  4. In vitro umbilical cord wrapping and torsion: possible cause of umbilical blood flow occlusion.

    Science.gov (United States)

    Bendon, Robert W; Brown, Shawn P; Ross, Michael G

    2014-09-01

    Intrapartum fetal heart rate decelerations and bradycardia are often attributed to umbilical cord occlusion without knowing the anatomic basis of that occlusion. We hypothesized that umbilical cord twisting while looped around fetal parts could occlude blood flow. Using an in vitro preparation, human umbilical cord veins were perfused at one end with water at approximately 40 cm H2O. The cords were looped around pipes that approximated the diameter of fetal body or limb parts, after which the perfused segment of cord was twisted until water flow stopped. The number of rotations needed to stop perfusion was recorded for each length of twisted cord (4, 6 and 8 cm) and for each pipe diameter. There were 21 completed studies. All cords demonstrated that a decreasing number of twists were needed to stop venous flow as the segment twisted became shorter (from 8 to 4 cm). For each segment length, the number of twists required to stop flow decreased as the pipe diameter narrowed. This model demonstrates that a wrapped umbilical cord, particularly with a short segment between the placental insertion and the fetal body part, may be predisposed to cord occlusion in response to fetal rotation.

  5. Use of cost-effectiveness analysis to determine inventory size for a national cord blood bank.

    Science.gov (United States)

    Howard, David H; Meltzer, David; Kollman, Craig; Maiers, Martin; Logan, Brent; Gragert, Loren; Setterholm, Michelle; Horowitz, Mary M

    2008-01-01

    Transplantation with stem cells from stored umbilical cord blood units is an alternative to living unrelated bone marrow transplantation. The larger the inventory of stored cord units, the greater the likelihood that transplant candidates will match to a unit, but storing units is costly. The authors present the results of a study, commissioned by the Institute of Medicine, as part of a report on the establishment of a national cord blood bank, examining the optimal inventory level. They emphasize the unique challenges of undertaking cost-effectiveness analysis in this field and the contribution of the analysis to policy. The authors estimate the likelihood that transplant candidates will match to a living unrelated marrow donor or a cord blood unit as a function of cord blood inventory and then calculate the life-years gained for each transplant type by match level using historical data. They develop a model of the cord blood inventory level to estimate total costs as a function of the number of stored units. The cost per life-year gained associated with increasing inventory from 50,000 to 100,000 units is $44,000 to $86,000 and from 100,000 to 150,000 units is $64,000 to $153,000, depending on the assumption about the degree to which survival rates for cord transplants vary by match quality. Expanding the cord blood inventory above current levels is cost-effective by conventional standards. The analysis helped shape the Institute of Medicine's report, but it is difficult to determine the extent to which the analysis influenced subsequent congressional legislation.

  6. Banking cord blood stem cells: attitude and knowledge of pregnant women in five European countries.

    Science.gov (United States)

    Katz, Gregory; Mills, Antonia; Garcia, Joan; Hooper, Karen; McGuckin, Colin; Platz, Alexander; Rebulla, Paolo; Salvaterra, Elena; Schmidt, Alexander H; Torrabadella, Marta

    2011-03-01

    This study explores pregnant women's awareness of cord blood stem cells and their attitude regarding banking options in France, Germany, Italy, Spain, and the UK. Questionnaires were distributed in six maternities. This anonymous and self-completed questionnaire included 29 multiple-choice questions based on: 1) sociodemographic factors, 2) awareness and access to information about cord blood banking, 3) banking option preferences, and 4) donating cord blood units (CBUs) to research. A total of 79% of pregnant women had little awareness of cord blood banking (n = 1620). A total of 58% of women had heard of the therapeutic benefits of cord blood, of which 21% received information from midwives and obstetricians. A total of 89% of respondents would opt to store CBUs. Among them, 76% would choose to donate CBUs to a public bank to benefit any patient in need of a cord blood transplant. Twelve percent would choose a mixed bank, and 12%, a private bank. A total of 92% would donate their child's CBU to research when it is not suitable for transplantation. The study reveals a strong preference for public banking in all five countries, based on converging values such as solidarity. Attitudes of pregnant women are not an obstacle to the rapid expansion of allogeneic banking in these EU countries. Banking choices do not appear to be correlated with household income. The extent of commercial marketing of cord blood banks in mass media highlights the importance for obstetric providers to play a central role in raising women's awareness early during their pregnancy with evidence-based medical information about banking options. © 2010 American Association of Blood Banks.

  7. Results of the Cord Blood Transplantation Study (COBLT) : clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies

    NARCIS (Netherlands)

    Kurtzberg, Joanne; Prasad, Vinod K.; Carter, Shelly L.; Wagner, John E.; Baxter-Lowe, Lee Ann; Wall, Donna; Kapoor, Neena; Guinan, Eva C.; Feig, Stephen A.; Wagner, Elizabeth L.; Kernan, Nancy A.

    2008-01-01

    Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching

  8. Results of the Cord Blood Transplantation Study (COBLT) : clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies

    NARCIS (Netherlands)

    Kurtzberg, Joanne; Prasad, Vinod K.; Carter, Shelly L.; Wagner, John E.; Baxter-Lowe, Lee Ann; Wall, Donna; Kapoor, Neena; Guinan, Eva C.; Feig, Stephen A.; Wagner, Elizabeth L.; Kernan, Nancy A.

    2008-01-01

    Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching

  9. Collection, processing and testing of bone, corneas, umbilical cord blood and haematopoietic stem cells by European Blood Alliance members

    DEFF Research Database (Denmark)

    Närhi, M; Natri, O; Desbois, I;

    2013-01-01

    A questionnaire study was carried out in collaboration with the European Blood Alliance (EBA) Tissues and Cells (T&C) working group. The aim was to assess the level of involvement and commonality of processes on the procurement, testing and storage of bone, corneas, umbilical cord blood (UCB...

  10. Transactivating-transduction protein-polyethylene glycol modified liposomes traverse the blood-spinal cord and blood-brain barriers

    Institute of Scientific and Technical Information of China (English)

    Xianhu Zhou; Chunyuan Wang; Shiqing Feng; Jin Chang; Xiaohong Kong; Yang Liu; Shijie Gao

    2012-01-01

    Naive liposomes can cross the blood-brain barrier and blood-spinal cord barrier in small amounts. Liposomes modified by a transactivating-transduction protein can deliver antibiotics for the treatment of acute bacterial infection-induced brain inflammation. Liposomes conjugated with polyethylene glycol have the capability of long-term circulation. In this study we prepared transactivating-transduction protein-polyethylene glycol-modified liposomes labeled with fluorescein isothiocyanate. Thus, liposomes were characterized by transmembrane, long-term circulation and fluorescence tracing. Uptake, cytotoxicity, and the ability of traversing blood-spinal cord and blood-brain barriers were observed following coculture with human breast adenocarcinoma cells (MCF-7). Results demonstrated that the liposomes had good biocompatibility, and low cytotoxicity when cocultured with human breast adenocarcinoma cells. Liposomes could traverse cell membranes and entered the central nervous system and neurocytes through the blood-spinal cord and blood-brain barriers of rats via the systemic circulation. These results verified that fluorescein isothiocyanate-modified transactivating-transduction protein-polyethylene glycol liposomes have the ability to traverse the blood-spinal cord and blood-brain barriers.

  11. Certain Red Blood Cell Indices of Maternal and Umbilical Cord ...

    African Journals Online (AJOL)

    Uche

    umbilical cord packed cell volume and haemoglobin concentration in our locality. Keywords: Umbilical ... parasitaemia, or had premature delivery, history of haemorheological ... labour (immediately after delivery) by clamping and cutting the ...

  12. Transfer of maternal IgE can be a common cause of increased IgE levels in cord blood

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Pipper, Christian Bressen; Bisgaard, Hans

    2010-01-01

    IgE in cord blood is thought to be a product of the fetus. A high level of total IgE is therefore used as a measure of atopic propensity in the newborn. We recently found strong evidence that allergen-specific IgE in cord blood was the result of transfer of maternal IgE to fetal blood or cord blood...... (maternofetal transfer) rather than fetal production. This also suggests that total IgE in cord blood might primarily be a maternal product....

  13. 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.

  14. Ethical issues relating the the banking of umbilical cord blood in Mexico

    Directory of Open Access Journals (Sweden)

    Valdez-Martinez Edith

    2009-08-01

    Full Text Available Abstract Background Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico. Discussion A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord. Summary Conflicts between moral principles and economic interests (non-moral principles cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks

  15. 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

  16. MicroRNA expression profiles in umbilical cord blood cell lineages.

    Science.gov (United States)

    Merkerova, Michaela; Vasikova, Alzbeta; Belickova, Monika; Bruchova, Hana

    2010-01-01

    MicroRNAs (miRNAs), important regulators of cellular processes, show specific expression signatures in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation, indicating their role in the control of hematopoiesis. Because neonatal blood displays various features of immaturity, we might expect differential miRNA regulation. Herein, we determined miRNA expression profiles of umbilical cord blood (UCB) cell lineages and compared them to those of bone marrow (BM) and peripheral blood (PB) cell counterparts. Further, we determined mRNA expression profiles using whole-genome microarrays. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative targets of miRNAs with potential functions in UCB. We pointed out several differentially expressed miRNAs and associated their expression with the target transcript levels. miR-148a expression was suppressed in HSCs and its level inversely correlated with the previously verified target, DNA methyltransferase 3B, suggesting dependence of de novo DNA methylation in HSCs on miR-148a. Prolonged cell survival of UCB HSCs may be associated with low expression of miR-143 and miR-145 and up-regulation of their downstream targets (high expression of c-MYC and miR-17-92 and following repression of TGFBR2). In HSCs, we monitored significant up-regulation of eight miRNAs, which were previously verified as regulators of HOX genes. Further, miR-146b may be associated with immaturity of neonatal immune system because it is strongly up-regulated in UCB granulocytes and T lymphocytes compared to PB cell counterparts. Comparative analysis revealed 13 miRNAs significantly altered between UCB and BM CD34(+) cells. In UCB CD34(+) cells, we monitored up-regulation of miR-520h, promoting differentiation of HSCs into progenitor cells, and reduction of miR-214, whose expression might support HSC survival. In conclusion, UCB cells show specific mi

  17. Comparison of Maternal and Umbilical Cord Blood Selenium Levels in Low and Normal Birth Weight Neonates

    Directory of Open Access Journals (Sweden)

    Lyly Nazemi

    2015-10-01

    Full Text Available Objective:To compare the maternal and umbilical cord serum selenium concentrations in Low and normal birth weight neonates.Materials and methods:A case-control study was carried out in Vali-Asr and Akbarabadi Hospitals (Jan. to Dec. 2013. Two groups; case group; 91 mothers who delivered a low birth weight (LBW neonate and control group; 86 subjects who delivered a normal birth weight neonate were selected. Immediately after birth, 5 ml of maternal blood and umbilical cord blood were collected, and sent to laboratory to assay Se concentrations. To compare both groups' blood Se concentration, data were analyzed in SPSS 16.0.Results:Eighty six (48.6% mothers with normal birth weight neonates and 91 (51.4% mothers with low birth weight infants entered the study. Mean maternal mothers' age and mean maternal blood Se were 28.55+5.90 years and 79.3756+26.46915. A significant association was seen between maternal blood and cord blood Se level in control and case group (P value<0.0001, r = 0.69 and(P value<0.001, r = 0.79. On the other hand no differences were seen between 2 groups' maternal blood Se level (P Value = 0.65. Umbilical Cord blood Se concentration was not also different between case and control group (P value = 0.46.Conclusion:We found that maternal and umbilical cord blood Se concentrations were not different in low and adequate birth weight infants, however; umbilical cord Se concentrations were positively correlated with maternal blood Se concentrations.

  18. Residual blood volume in the umbilical cord of extremely premature infants.

    Science.gov (United States)

    Hosono, Shigeharu; Hine, Kotaro; Nagano, Nobuhiko; Taguchi, Yosuke; Yoshikawa, Kayo; Okada, Tomoo; Mugishima, Hideo; Takahashi, Shigeru; Takahashi, Shori

    2015-01-01

    The aim of this study was to investigate residual blood volume in the umbilical cord of extremely premature infants. Twenty extremely premature infants were held at or below the placenta while the umbilical cord was clamped and cut at approximately 2-3 cm from the umbilicus within 30 s after birth. The umbilical cord was then clamped near the placenta to obtain a length of approximately 30 cm and cut. The residual blood volume in the segment of cord was drained and measured in milliliters. Mean birthweight was 846 ± 172 g (range, 587-1180 g). The average length of the clamped segment of umbilical cord was 29.8 ± 1.5 cm (range, 27-32 cm). Total residual blood volume and residual blood volume per cm were 15.5 ± 6.7 mL (range, 6-25 mL) and 0.5 ± 0.2 mL/cm (range, 0.2-0.8 mL/cm), respectively. The residual cord blood volume per kilogram of infant weight per 30 cm was 17.7 ± 5.5 mL/kg/30 cm (range, 8.9-29.0 mL/kg/30 cm). Infants could receive approximately 18 mL/kg of whole blood by one-time milking of 30 cm umbilical cord. With an average hematocrit of 40%, this volume is equivalent to approximately 13 mL of packed red blood cells (hematocrit 55%). © 2014 Japan Pediatric Society.

  19. Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Behzad-Behbahani A

    2008-01-01

    Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

  20. Lead, mercury, and organochlorine compound levels in cord blood in Québec, Canada.

    Science.gov (United States)

    Rhainds, M; Levallois, P; Dewailly, E; Ayotte, P

    1999-01-01

    We conducted this study to evaluate blood levels of lead, mercury, and organochlorine compounds in newborns in the Province of Quebec. During 1993 to 1995, we carried out a survey in 10 hospitals located in southern Quebec. During that time, umbilical cord blood samples were obtained from 1109 newborns, and we analyzed each for lead, mercury, 14 polychlorinated biphenyl congeners, and 11 chlorinated pesticides. We used the geometric mean and 95% confidence interval (CI) to describe the results. Mean concentrations of lead and mercury in cord blood were 0.076 micromol/l (95% CI = 0.074, 0.079) and 4.82 nmol/l (95% CI = 4.56, 5.08), respectively. The mean concentrations of total polychlorinated biphenyls (Aroclor 1260) and dichlorodiphenyl dichloroethylene were 0.514 microg/I (95% CI = .493, 0.536) and 0.412 microg/l (95% CI = 0.390, 0.435), respectively. We observed a statistically significant relationship between maternal age and cord blood concentrations of (a) lead, (b) mercury, (c) polychlorinated biphenyls, and (d) dichlorodiphenyl dichloroethylene. In addition, maternal smoking during pregnancy was associated with cord blood lead levels. The cord blood concentrations of lead, mercury, polychlorinated biphenyls, and dichlorodiphenyl dichloroethylene we measured in our study were the lowest levels recently reported in industrialized countries. The results of this study underline the role of public health authorities in the evaluation of biological levels of environmental contaminants among children for the assessment of risk of adverse health effects.

  1. Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Youngjeon Lee

    2014-01-01

    Full Text Available Endogenous neural stem/progenitor cells (eNSPCs proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI. We have previously shown that melatonin (MT plus exercise (Ex had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups.These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.

  2. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Thomsen, Preben Dybdahl; Betts, Dean H.

    2009-01-01

      BACKGROUND AIMS: A robust methodology for the isolation of cord blood-derived multipotent mesenchymal stromal cells (CB-MSCs) from fresh umbilical cord blood has not been reported in any species. The objective of this study was to improve the isolation procedure for equine CB-MSCs. METHODS: Pre-culture...... separation of red and white blood cells was done using either PrepaCyte?-EQ medium or Ficoll-Paque? PREMIUM density medium. Regular FBS and MSC-qualified FBS were compared for their ability to support the establishment of putative primary MSC colonies. RESULTS AND CONCLUSIONS: Our results indicate that Prepa...

  3. Manganese concentration in the spinal cords and blood corpuscles of amyotrophic lateral sclerosis patients

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Satoru; Toyoshima, Masanori; Otsuki, Yuzo; Nagata, Hiroshi; Nakamura, Shigenobu (Kyoto Univ. (Japan). Faculty of Medicine)

    1981-11-01

    Manganese concentration in the spinal cord tissues and the blood corpuscles from patients with amyotrophic lateral sclerosis (ALS) and other diseases were measured by neutron activation analysis. The mean manganese concentration in the spinal cord from ALS patients was significantly higher than that from control subjects, especially in the anterior horn of the cervical cord. In order to determine the manganese concentration in blood corpuscles by neutron activation analysis, it was necessary to subtract /sup 56/Mn derived from the /sup 56/Fe(n, p)/sup 56/Mn reaction. The mean Mn concentration in the blood corpuscles from ALS patients seems to be lower than that from patients with other diseases. Fe, Se, Rb and Zn concentrations in the blood corpuscles from ALS patients were not different from those of patients with other diseases.

  4. Thrombopoietin concentration in umbilical cord blood of healthy term newborns is higher than in adult controls.

    Science.gov (United States)

    Walka, M M; Sonntag, J; Dudenhausen, J W; Obladen, M

    1999-01-01

    Thrombopoietin (TPO) concentrations were determined in umbilical cord plasma of 121 healthy term newborns. The lower detection limit of the enzyme immunoassay employed was 32.5 pg/ml. Median cord plasma TPO concentration was 78 (interquartile range 55-107) pg/ml. 95th percentile was 255 pg/ml. In only 8% (10/121), TPO was below the detection limit compared to 81% of healthy adults (25/31). In cord blood and adult controls, there were no significant correlations of TPO with platelet count or mass.

  5. In vitro study of the influence of GST-π gene transfer on drug-resistance of human cord blood CD34 + cells

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective: To investigate the influence of GST-π gene transfer on drug-resis-tance of human cord blood CD34+ cells. Methods:CD34+ cells were purified from cord blood fromnormal full-term pregnancy. Gene transduction into human cord blood CD34 + cells was carried outusing GST-π gene containing retrovirus vector. The GST-π gene expression in transduced CD34 +cell was confirmed by RT-PCR. After confirmation of GST-π gene transfer, the transfected CD34 +cells were cultured by colony assay in the presence of carboplatin. Results:GST-π mRNA was de-tected in 30% of CFU-GM derived from GST-π gene transduced CD34+ cells. In vitro drug resis-tance test showed that the number of CFU-GM formed was significantly higher (2 ~ 3 fold) in GST-π gene transduced CD34+ cells than untransduced CD34+ cells. Conclusion:GST-π gene transfercan confer resistance to hematopoietic progenitors against carboplatin in vitro.

  6. Umbilical blood flow patterns directly after birth before delayed cord clamping.

    Science.gov (United States)

    Boere, I; Roest, A A W; Wallace, E; Ten Harkel, A D J; Haak, M C; Morley, C J; Hooper, S B; te Pas, A B

    2015-03-01

    Delayed umbilical cord clamping (DCC) affects the cardiopulmonary transition and blood volume in neonates immediately after birth. However, little is known of blood flow in the umbilical vessels immediately after birth during DCC. The objective is to describe the duration and patterns of blood flow through the umbilical vessels during DCC. Arterial and venous umbilical blood flow was measured during DCC using Doppler ultrasound in uncomplicated term vaginal deliveries. Immediately after birth, the probe was placed in the middle of the umbilical cord, pattern and duration of flow in vein and arteries were evaluated until cord clamping. Thirty infants were studied. Venous flow: In 10% no flow was present, in 57% flow stopped at 4:34 (3:03-7:31) (median (IQR) min:sec) after birth, before the cord was clamped. In 33%, flow continued until cord clamping at 5:13 (2:56-9:15) min:sec. Initially, venous flow was intermittent, increasing markedly during large breaths or stopping and reversing during crying, but then became continuous. Arterial flow: In 17% no flow was present, in 40% flow stopped at 4:22 (2:29-7:17) min:sec, while cord pulsations were still palpable. In 43% flow continued until the cord was clamped at 5:16 (3:32-10:10) min:sec. Arterial flow was pulsatile, unidirectional towards placenta or bidirectional to/from placenta. In 40% flow became continuous towards placenta later on. During delayed umbilical cord clamping, venous and arterial umbilical flow occurs for longer than previously described. Net placental transfusion is probably the result of several factors of which breathing could play a major role. Umbilical flow is unrelated to cessation of pulsations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Optical measurement of blood flow changes in spinal cord injury

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, J P; Kyriacou, P A [Biomedical Engineering Research Group, City University London, Northampton Square, London (United Kingdom); George, K J [Neuroscience Centre, Queen Mary, University of London, Mile End, London (United Kingdom); Langford, R M, E-mail: justin.phillips.1@city.ac.u [Pain and Anaesthesia Research Centre, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

    2010-07-01

    Little is known about cell death in spinal cord tissue following compression injury, despite compression being a key component of spinal injuries. Currently models are used to mimic compression injury in animals and the effects of the compression evaluated by observing the extent and duration of recovery of normal motor function in the days and weeks following the injury. A fibreoptic photoplethysmography system was used to investigate whether pulsation of the small arteries in the spinal cord occurred before, during and after compressive loads were applied to the tissue. It was found that the signal amplitudes were reduced and this reduction persisted for at least five minutes after the compression ceased. It is hoped that results from this preliminary study may improve knowledge of the mechanism of spinal cord injury.

  8. Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus.

    Science.gov (United States)

    He, Binbin; Li, Xia; Yu, Haibo; Zhou, Zhiguang

    2015-11-01

    Type 1 diabetes mellitus (T1DM) is a chronic disorder that results from autoimmune-mediated destruction of pancreatic islet β-cells. However, to date, no conventional intervention has successfully treated the disease. The optimal therapeutic method for T1DM should effectively control the autoimmunity, restore immune homeostasis, preserve residual β-cells, reverse β-cell destruction, and protect the regenerated insulin-producing cells against re-attack. Umbilical cord blood is rich in regulatory T (T(reg)) cells and multiple types of stem cells that exhibit immunomodulating potential and hold promise in their ability to restore peripheral tolerance towards pancreatic islet β-cells through remodeling of immune responses and suppression of autoreactive T cells. Recently, reinfusion of autologous umbilical cord blood or immune cells from cord blood has been proposed as a novel therapy for T1DM, with the advantages of no risk to the donors, minimal ethical concerns, a low incidence of graft-versus-host disease and easy accessibility. In this review, we revisit the role of autologous umbilical cord blood or immune cells from cord blood-based applications for the treatment of T1DM.

  9. Cord blood dendritic cell subsets in African newborns exposed to Plasmodium falciparum in utero.

    Science.gov (United States)

    Breitling, Lutz P; Fendel, Rolf; Mordmueller, Benjamin; Adegnika, Ayola A; Kremsner, Peter G; Luty, Adrian J F

    2006-10-01

    Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring of Gabonese mothers with different infection histories. Cord blood from newborns of mothers with malarial infection at delivery had significantly more mDC than that from nonexposed newborns (P = 0.028) but mDC and pDC HLA-DR expression was unrelated to maternal infection history. Independently of these findings, cord blood mDC and pDC numbers declined significantly as a function of increasing maternal age (P = 0.029 and P = 0.033, respectively). The inducible antigen-specific interleukin-10-producing regulatory-type T-cell population that we have previously detected in cord blood of newborns with prolonged in utero exposure to P. falciparum may directly reflect the altered DC numbers in such neonates, while the maintenance of cord blood DC HLA-DR expression contrasts with that of DC from P. falciparum malaria patients.

  10. 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).

  11. Expansion of CD34+ cells from human umbilical cord blood by FL and/or TPO gene transfected human marrow stromal cell lines

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Yi(

    2001-01-01

    [1]Luens. K. M., Travis, M. A., Chen, B. P. et al., Thrombopoietin, kit ligand, and flk2/flt3 ligand together induce increased numbers of primitive hematopoietic progenitors from human CD34+Thy+Lin cells with preserved ability to engraft SCID-hu bone, Blood, 1998, 91: 1206-1215.[2]Piacibello, W., Sanavio, F., Garetto, L. et al., Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood, Blood, 1997, 89(8)L 2644-2653.[3]Zhang Yi, Tang Peixian, Li Xiusen et al., Expression of human FL ligand and thrombopoietin genes in a bone marrow stromal cell line by internal ribosome entry site (IRES) sequence, Chin. J. Hematol. (in Chinese), 1999, 20(12): 624-627.[4]Zhou. S., Mao, N., Zhao, M. et al., Effect of recombinant FLT3 ligand (rhFL) on in vitro expansion of human cord blood CD34+ cells. Natl. Med. J. China, 1998, 78: 37-39.[5]Dexter. T. M.. Allen, T. D., Lajtha, L. G. et al., Conditions controlling the proliferation of hematopoietic stem cells in vitro,J. Cell Physiol.. 1997, 91: 335-344.[6]Petzer. A. L., Hogge, D. E.. Lansdorp, P. M. et al., Self-renewal of primitive human hematopoietic cells (long-term-culture-initiating cells) in vitro and their expansion in defined medium, Pro. Natl. Acad. Sci. USA, 1996, 93:1470-1474.[7]Sirchia, G., Rebulla, P., Placental/umbilical cord blood transplantation, Haematologica, 1999, 84: 738-747.[8]Wineman, J., Moore, K., Lemischka, I. et al., Functional heterogeneity of the hematopoietic microenvironment: Rare stromal elements maintain long-term repopulating stem cells, Blood, 1996, 87: 4082-4090.[9]Szilvassy, S. J., Weller, K. P., Lin, W. et al., Leukemia inhibitory factor upregulates cytokine expression by a murine stromal cell line enabling the maintenance of highly enriched competitive repopulating stem cells, Blood, 1996, 87:4618-4628.[10]Aiuti, A., Fredrich, C., Sieff, C. A. et al., Identification of distinct elements of the stromal

  12. Prenatal exposure to lead in Spain: Cord blood levels and associated factors

    Energy Technology Data Exchange (ETDEWEB)

    Llop, Sabrina, E-mail: llop_sab@gva.es [Centre of Public Health Research (CSISP), Av Catalunya 21, 46020, Valencia (Spain); Carlos III Health Institute (ISCIII), 20220 Majadahonda, Madrid (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Aguinagalde, Xabier [Public Health Laboratory of Alava, Direccion de Salud Publica, Gobierno Vasco, Santiago 11, 01002, Vitoria-Gasteiz, Basque Country (Spain); Vioque, Jesus [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Universidad Miguel Hernandez, Av de Alicante KM 87, 03550, Sant Joan d' Alacant (Spain); Ibarluzea, Jesus [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Departamento de Sanidad Gobierno Vasco, Subdireccion de Salud Publica de Gipuzkoa, Avenida de Navarra 4, 20013 San Sebastian (Spain); Biodonostia, Instituto de Investigacion Biomedica, San Sebastian (Spain); Guxens, Monica [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); Casas, Maribel [Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); Murcia, Mario [Centre of Public Health Research (CSISP), Av Catalunya 21, 46020, Valencia (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Ruiz, Maria [Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); and others

    2011-05-01

    Introduction and Objective: Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). Methods: A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. {>=} vs < 2 {mu}g/dL). Results: A low percentage of cord blood samples with lead levels {>=} 2 {mu}g/dL were found (5.9%). Geometric mean and maximum were 1.06 {mu}g/dL and 19 {mu}g/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels {>=} 2 {mu}g/dL. Conclusion: In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. - Research Highlights: {yields} Pb is a ubiquitous environmental pollutant with harmful effects on neurodevelopment. {yields} Cord blood Pb levels in

  13. Comparison of Stored Umbilical Cord Blood and Adult Donor Blood: Transfusion Feasibility

    Directory of Open Access Journals (Sweden)

    Rola Sahyoun-tokan

    2012-09-01

    Full Text Available OBJECTIVE: This study aimed to compare the storage properties of red blood cell (RBC concentrates of umbilical cord blood (UCB and adult donor blood (ADB, and to evaluate the feasibility of UCB-RBC concentrate as an autologous source for blood transfusion in very low birth weight (VLBW preterm neonates. METHODS: In all, 30 newborn (10 preterm, 20 full term UCB and 31 ADB units were collected. RBC concentrates were stored and compared with regard to pH, potassium (K+, 2,3-biphosphoglycerate (2-3-BPG, adenosine tri-phosphate (ATP, plasma Hb, and bacterial contamination on d 1, 21, and 35 of storage. RESULTS: The K+ level increased with time and differed significantly between storage d 1 and 21, and between storage d 1 and 35 in both the UCB and ADB units. Initial and d 21 K+ levels were higher in the UCB units than in the ADB units. The 2,3-BPG level did not differ significantly between the UCB-PRC and ADB-PRC samples. After 35 d of storage both UCB-PRC and ADB-PRC samples exhibited significant differences from the initial free Hb, intracellular ATP, and pH values. Significant differences in intracellular ATP and pH were also observed between the UCB-PRC and ADB-PRC samples. CONCLUSION: The volume of harvested and prepared UCB-PRC can be used for some of the blood transfusions required during the neonatal period and thus may decrease the number of allogeneic transfusions, especially in preterm newborns. The hematological and biochemical changes that occurred in UCB during storage were comparable with those observed in ADB, and do not pose a risk to the immature metabolism of neonates. UCB-RPC prepared and stored under standard conditions can be a safe alternative RBC source for transfusions in VLBW newborns.

  14. Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs.

    Science.gov (United States)

    Morin, Alexander M; Gatev, Evan; McEwen, Lisa M; MacIsaac, Julia L; Lin, David T S; Koen, Nastassja; Czamara, Darina; Räikkönen, Katri; Zar, Heather J; Koenen, Karestan; Stein, Dan J; Kobor, Michael S; Jones, Meaghan J

    2017-01-01

    Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.

  15. Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation.

    Science.gov (United States)

    Horwitz, Mitchell E

    2016-02-01

    The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.

  16. Role of ERK1/2, Akt, and PLCy pathways in proliferation and neuronal differentiation in the adult rat spinal cord neural stem/progenitor cell culture

    Directory of Open Access Journals (Sweden)

    Wai Si eChan

    2013-08-01

    Full Text Available Proliferation of endogenous neural stem/progenitor cells (NSPCs has been identified in both normal and injured adult mammalian spinal cord. Yet the signaling mechanisms underlying the regulation of adult spinal cord NSPCs proliferation and commitment toward a neuronal lineage remain undefined. In this study, the role of three growth factor-mediated signaling pathways in proliferation and neuronal differentiation was examined. Adult spinal cord NSPCs were enriched in the presence of fibroblast growth factor 2 (FGF2. We observed an increase in the number of cells expressing the microtubule-associated protein 2 (MAP2 over time, indicating neuronal differentiation in the culture. Inhibition of the mitogen-activated protein kinase or extracellular signal-regulated kinase (ERK kinase 1 and 2/ERK 1 and 2 (MEK/ERK1/2 or the phosphoinositide 3-kinase (PI3K/Akt pathways suppressed active proliferation in adult spinal cord NSPC cultures; whereas neuronal differentiation was negatively affected only when the ERK1/2 pathway was inhibited. Inhibition of the phospholipase C gamma (PLCy pathway did not affect proliferation or neuronal differentiation. Finally, we demonstrated that the blockade of either the ERK1/2 or PLCy signaling pathways reduced neurite branching of MAP2+ cells derived from the NSPC cultures. Many of the MAP2+ cells expressed synaptophysin and had a glutamatergic phenotype, indicating that over time adult spinal cord NSPCs had differentiated into mostly glutamatergic neurons. Our work provides new information regarding the contribution of these pathways to the proliferation and neuronal differentiation of NSPCs derived from adult spinal cord cultures, and emphasizes that the contribution of these pathways is dependent on the origin of the NSPCs.

  17. Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Ji Cheol Shin

    2015-01-01

    Full Text Available In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs transplanted into the injured cord after traumatic cervical spinal cord injury (SCI. Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS grade improved in 5 of 19 transplanted patients, 2 (A → C, 1 (A → B, and 2 (B → D, whereas only one patient in the control group showed improvement (A → B. Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS, Registration Number: KCT0000879.

  18. [Knockdown of Puma protects cord blood CD34(+) cells against γ- irradiation].

    Science.gov (United States)

    Zhao, Lei; Zhang, Hong-Yan; Pang, Ya-Kun; Gu, Hai-Hui; Xu, Jing; Yuan, Wei-Ping; Cheng, Tao

    2014-04-01

    Puma (P53 upregulated modulator of apoptosis) is a BCL-2 homology 3 (BH3)-only BCL-1 family member and a critical mediator of P53-dependent and -independent apoptosis. Puma plays an essential role in the apoptosis of hematopoietic stem cells exposed to irradiation without an increased risk of malignancies. This study was purposed to develop an effective lentiviral vector to target Puma in human hematopoietic cells and to investigate the effect of Puma gene knockdown on the biological function of human cord blood CD34(+) cells. SF-LV-shPuma-EGFP and control vectors were constructed, and packaged with the pSPAX2/pMD2.G packaging plasmids via 293T cells to produce pseudo-type lentiviruses. SF-LV-shPuma-EGFP or control lentiviruses were harvested within 72 hours after transfection and then were used to transduce human cord blood CD34(+) cells. GFP(+) transduced cells were sorted by flow cytometry (FCM) for subsequent studies. Semi-quantitative real time RT PCR, Western blot, FCM with Annexin V-PE/7-AAD double staining, Ki67 staining, colony forming cell assay (CFC), CCK-8 assay and BrdU incorporation were performed to determine the expression of Puma and its effect on the cord blood CD34(+) cells. The results showed that Puma was significantly knocked down in cord blood CD34(+) cells and the low expression of Puma conferred a radio-protective effect on the cord blood CD34(+) cells. This effect was achieved through reduced apoptosis and sustained quiescence after irradiation due to Puma knockdown. It is concluded that knockdown of puma gene in CD34(+) hematopoietic stem cells of human cord blood possesses the radioprotective effect, maintains the cells in silence targeting Puma in human hematopoietic cells may have a similar effect with that on mouse hematopoietic cells as previously shown, and our lentiviral targeting system for Puma provides a valuable tool for future translational studies with human cells.

  19. Impaired function of regulatory T cells in cord blood of children of allergic mothers.

    Science.gov (United States)

    Hrdý, J; Kocourková, I; Prokešová, L

    2012-10-01

    Allergy is one of the most common diseases with constantly increasing incidence. The identification of prognostic markers pointing to increased risk of allergy development is of importance. Cord blood represents a suitable source of cells for searching for such prognostic markers. In our previous work, we described the increased reactivity of cord blood cells of newborns of allergic mothers in comparison to newborns of healthy mothers, which raised the question of whether or not this was due to the impaired function of regulatory T cells (T(regs)) in high-risk children. Therefore, the proportion and functional properties of T(regs) in cord blood of children of healthy and allergic mothers were estimated by flow cytometry. The proportion of T(regs) [CD4(+)CD25(high)CD127(low) forkhead box protein 3 (FoxP3(+))] in cord blood of children of allergic mothers tends to be higher while, in contrast, the median of fluorescence intensity of FoxP3 was increased significantly in the healthy group. Intracellular presence of regulatory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-beta was also higher in T(regs) of children of healthy mothers. Although we detected an increased proportion of T(regs) in cord blood of children of allergic mothers, the functional indicators (intracellular presence of regulatory cytokines IL-10 and TGF-beta, median of fluorescence intensity of FoxP3) of those T(regs) were lower in comparison to the healthy group. We can conclude that impaired function of T(regs) in cord blood of children of allergic mothers could be compensated partially by their increased number. Insufficient function of T(regs) could facilitate allergen sensitization in high-risk individuals after subsequent allergen encounter. © 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.

  20. 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.

  1. Contribution of gestational exposure to ambient traffic air pollutants to fetal cord blood manganese.

    Science.gov (United States)

    Lin, Ying-Ying; Hwang, Yaw-Huei; Chen, Pau-Chung; Chen, Bing-Yu; Wen, Hui-Ju; Liu, Jyung-Hung; Guo, Yue Leon

    2012-01-01

    Motor vehicle emissions have become a major source of air pollution. Contributions of motor vehicle emissions to exposure to toxic metals such as manganese remain inconclusive. This study investigates the relationship between the concentration of manganese in cord blood and exposure to criteria air pollutants during pregnancy. A total of 1526 mother-newborn pairs were recruited by stratified sampling between April, 2004 and July, 2005. The newborns' mothers completed questionnaires that collected information on their demographic characteristics, medical histories, and living environments. Cord blood samples were collected at birth and analyzed by inductively coupled plasma mass spectrometry for manganese. Information about criteria air pollutants which included CO, NO(2), ozone, SO(2), and PM(10) was obtained from monitoring stations run by the Taiwan Environmental Agency. Using the Arc9 Geographic Information System's kriging method, the concentration of each criteria pollutant was estimated at each newborn's residence. The geometric mean for cord blood manganese concentrations was 47.0 μg/L (GSD=1.4). After adjusting for confounding factors such as family income, maternal education, maternal smoking, alcohol drinking during pregnancy, maternal age, child gender, parity, gestational age, and birth season, the results of a multiple linear regression model indicated that cord blood manganese concentration was significantly associated with NO(2) concentration in each trimester, as well as the whole duration of gestation. Between the pregnant women exposed to the highest and those to the lowest quartile of NO(2), a 6 μg/L difference in cord blood manganese concentration was found. This finding suggests that despite other sources of manganese exposure, maternal exposure to ambient NO(2), a surrogate for traffic emission, significantly contributed to fetal cord blood manganese level. Further study is warranted to determine whether the contribution of manganese due to

  2. Maternal and cord blood levels of aldrin and dieldrin in Delhi population.

    Science.gov (United States)

    Mustafa, Md; Pathak, Rahul; Tripathi, A K; Ahmed, Rafat S; Guleria, Kiran; Banerjee, B D

    2010-12-01

    Aldrin and dieldrin, structurally similar organochlorine pesticides belong to cyclodiene family and were widely used for agriculture and public health program in India. Although the manufacturing, use and import of aldrin and dieldrin have been banned in India since 2003, these pesticides are still persistent in environment and may be associated with adverse neurological and reproductive effects. The aim of this study is to assess the recent exposure level of aldrin and dieldrin and their placental transfer to fetus in normal healthy full-term pregnant women belonging to north Indian population undergoing normal delivery at Obstetrics and Gynecology department of UCMS and GTB hospital, Delhi. Quantitative analysis of aldrin and dieldrin residues in maternal and cord blood samples were carried out by gas chromatography system equipped with electron capture detector. The results of our study clearly revealed that maternal and cord blood levels of aldrin and dieldrin of pregnant women are age and dietary habit dependent. The aldrin level in maternal blood and dieldrin level in cord blood are higher in women in the age group 25-30 years than in women in age group of 19-24 years. Similarly, aldrin level in maternal blood is significantly higher in women with non-vegetarian dietary habit than in women with vegetarian dietary habit. No significant association is found for maternal and cord blood level. The results of the present study clearly demonstrate prenatal uptake of aldrin and dieldrin and provide recent information on the subsequent transplacental transfer.

  3. Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort.

    Science.gov (United States)

    Wilkinson, A L; Pedersen, S H; Urassa, M; Michael, D; Andreasen, A; Todd, J; Kinung'hi, S M; Changalucha, J; McDermid, J M

    2017-01-01

    HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort. A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry. Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery. Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  4. A Novel Population of Mesenchymal Progenitors with Hematopoietic Potential Originated from CD14- Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Gang Hu, Peng Liu, Jie Feng, Yan Jin

    2011-01-01

    Full Text Available Hemopoietic system derived progenitor cells with mesenchymal features have been identified including CD14+ monocyte-derived progenitors. However, it is unclear whether there are mesenchyme derived progenitors with hematopoietic potential. Herein, we identified a novel CD14- cell-derived population with both mesenchymal and hematopoietic features in rat peripheral blood, and this cell population is different from the CD14+ monocyte-derived progenitors but designated peripheral blood multipotential mesenchymal progenitors (PBMMPs. Phenotype analysis demonstrated expression of mesenchymal markers in PBMMPs including BMPRs, Endoglin/CD105, Fibronectin (Fn, Vimentin (Vim, Collagen (Col I/II/III along with hematopoietic marker CD34. CD14+ cell-derived population shared the same characteristics with CFs. In mixed culture of CD14+ and CD14- cells, PBMMPs were a predominant component and expressed CD29high, CD73high, CD34high, CD45low and CD90. Except for the value of mixed T lymphocytes and CD14+ cell-derived population, hematopoietic characters of cultured PBMMPs were indicated by CD14-/CD34+/CD45-/CD90+. The mesenchymal origin was further confirmed by comparing PBMMPs with bone marrow stromal cells. Finally, we transplanted PBMMPs into a skin wound model, and results showed the specific potential of PBMMPs in not only extracellular matrix secretion but epidermal regeneration. This study provides evidence that peripheral blood contains common hematopoietic-mesenchymal progenitors from both hematopoietic and mesenchymal lineages, and CD34+ mesenchymal progenitors are a possible alternative source of epidermal cells in wound healing.

  5. Maternal-Cord Blood Vitamin D Correlations Vary by Maternal Levels

    OpenAIRE

    2016-01-01

    Vitamin D levels of pregnant women and their neonates tend to be related; however, it is unknown whether there are any subgroups in which they are not related. 25-Hydroxyvitamin D [25(OH)D] was measured in prenatal maternal and child cord blood samples of participants (n = 241 pairs) in a birth cohort. Spearman correlations were examined within subgroups defined by prenatal and delivery factors. Cord blood as a percentage of prenatal 25(OH)D level was calculated and characteristics compared b...

  6. Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells.

    Science.gov (United States)

    Daud, Hasbullah; Browne, Susan; Al-Majmaie, Rasoul; Murphy, William; Al-Rubeai, Mohamed

    2016-01-25

    An understanding of the metabolic profile of cell proliferation and differentiation should support the optimization of culture conditions for hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and maturation into red blood cells. We have evaluated the key metabolic parameters during each phase of HSPC culture for red blood cell production in serum-supplemented (SS) and serum-free (SF) conditions. A simultaneous decrease in growth rate, total protein content, cell size, and the percentage of cells in the S/G2 phase of cell cycle, as well as an increase in the percentage of cells with a CD71(-)/GpA(+) surface marker profile, indicates HSPC differentiation into red blood cells. Compared with proliferating HSPCs, differentiating HSPCs showed significantly lower glucose and glutamine consumption rates, lactate and ammonia production rates, and amino acid consumption and production rates in both SS and SF conditions. Furthermore, extracellular acidification was associated with late proliferation phase, suggesting a reduced cellular metabolic rate during the transition from proliferation to differentiation. Under both SS and SF conditions, cells demonstrated a high metabolic rate with a mixed metabolism of both glycolysis and oxidative phosphorylation (OXPHOS) in early and late proliferation, an increased dependence on OXPHOS activity during differentiation, and a shift to glycolytic metabolism only during maturation phase. These changes indicate that cell metabolism may have an important impact on the ability of HSPCs to proliferate and differentiate into red blood cells.

  7. High quality cord blood banking is feasible with delayed clamping practices. The eight-year experience and current status of the national Swedish Cord Blood Bank.

    Science.gov (United States)

    Frändberg, Sofia; Waldner, Berit; Konar, Jan; Rydberg, Lennart; Fasth, Anders; Holgersson, Jan

    2016-09-01

    The National Swedish Cord Blood Bank (NS-CBB) is altruistic and publicly funded. Herein we describe the status of the bank and the impact of delayed versus early clamping on cell number and volume. Cord Blood Units (CBUs) were collected at two University Hospitals in Sweden. Collected volume and nucleated cell content (TNC) were investigated in 146 consecutive Cord Blood (CB) collections sampled during the first quarter of 2012 and in 162 consecutive CB collections done in the first quarter of 2013, before and after clamping practices were changed from immediate to late (60 s) clamping. NS-CBB now holds close to 5000 units whereof 30 % are from non-Caucasian or mixed origins. Delayed clamping had no major effect on collection efficiency. The volume collected was slightly reduced (mean difference, 8.1 ml; 95 % CI, 1.3-15.0 ml; p = 0.02), while cell recovery was not (p = 0.1). The proportion of CBUs that met initial total TNC banking criteria was 60 % using a TNC threshold of 12.5 × 10(8), and 47 % using a threshold of 15 × 10(8) for the early clamping group and 52 and 37 % in the late clamping group. Following implementation of delayed clamping practices at NS-CBB; close to 40 % of the collections in the late clamping group still met the high TNC banking threshold and were eligible for banking, implicating that that cord blood banking is feasible with delayed clamping practices.

  8. Wnt1 Accelerates an Ex Vivo Expansion of Human Cord Blood CD34+CD38− Cells

    Directory of Open Access Journals (Sweden)

    Kamonnaree Chotinantakul

    2013-01-01

    Full Text Available Cord blood hematopoietic stem cells (CB-HSCs transplantation has been increasing gradually with facing the limitation of insufficient quantity of HSCs in each CB unit. Therefore, efficient expansion methods which can maintain stem cell characteristics are needed. In this study, umbilical CB-CD34+ cells were cultured in two different cytokine cocktails: 4 factors (4F = Flt3-L, SCF, IL-6, and TPO and 5 factors (5F = Wnt1 + 4F in both serum and serum-free media. The data revealed that the best condition to accelerate an expansion of CD34+CD38− cells was serum-free culture condition supplemented with 5F (5F KSR. This condition yielded 24.3 ± 2.1 folds increase of CD34+CD38− cells. The expanded cells exhibited CD34+ CD38− CD133+ CD71low CD33low CD3− CD19− markers, expressed nanog, oct3/4, c-myc, and sox2 genes, and maintained differentiation potential into lymphoid, erythroid and myeloid lineages. The achievement of CD34+CD38− cells expansion may overcome an insufficient quantity of the cells leading to the improvement of the stem cell transplantation. Altogether, our findings highlight the role of Wnt1 and the new culture condition in stimulating hematopoietic stem/progenitor cells expansion which may offer a new therapeutic avenue for cord blood transplantation, regenerative medicine, stem cell bank applications, and other clinical applications in the future.

  9. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  10. Mercury levels in cord blood and meconium of healthy newborns and venous blood of their mothers: Clinical, prospective cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Unuvar, Emin [Istanbul University, Istanbul Medical Faculty, Department of Pediatrics, Istanbul (Turkey)]. E-mail: Eunuvar@superonline.com; Ahmadov, Hasan [Istanbul University, Istanbul Medical Faculty, Department of Pediatrics, Istanbul (Turkey); Kiziler, Ali Riza [Istanbul University, Istanbul Medical Faculty, Department of Pediatrics, Istanbul (Turkey); Istanbul University, Cerrahpasa Medical Faculty, Department of Biophysics, Istanbul (Turkey); Aydemir, Birsen [Istanbul University, Istanbul Medical Faculty, Department of Pediatrics, Istanbul (Turkey); Istanbul University, Cerrahpasa Medical Faculty, Department of Biophysics, Istanbul (Turkey); Toprak, Sadik [Gazi Osman Pasa University, Department of Forensic Pathology, Tokat (Turkey); Ulker, Volkan [Bakirkoy Government Hospital, Istanbul (Turkey); Ark, Cemal [Bakirkoy Government Hospital, Istanbul (Turkey)

    2007-03-01

    Objectives: The purpose of this study is to investigate the chronic mercury intoxication in pregnant women and newborns living in Istanbul, Turkey. Methods: The research was carried out as a prospective with 143 pregnant women and their newborns. Venous blood from the mother, cord blood from the neonate, and meconium were collected for mercury analysis. Frequency of fish and vegetable-eating and the number of teeth filled were investigated. Analyses were made in cold vapor Atomic Absorption Spectrophotometer (AAS, {mu}g/L). Results: Mercury levels were 0.38 {+-} 0.5 {mu}g/L (0-2.34) in venous blood of pregnant women, 0.50 {+-} 0.64 {mu}g/L (0-2.36) in umbilical cord blood and 9.45 {+-} 13.8 {mu}g/g (0-66.5) in meconium. Maternal blood mercury level was lower than the known toxic limit for humans (EPA, 5 {mu}g/L). Mercury levels of the maternal venous blood were significantly correlated with umbilical cord blood. The primary risk factors affecting mercury levels were eating fishmeals more than twice a week and having filled teeth more than five. The fact that the mother had a regular vegetable diet everyday reduced the mercury levels. Increased levels of mercury in the mother and umbilical cord blood could lead to retarded newborns' weight and height. Conclusion: Pregnant women living in Istanbul may be not under the risk of chronic mercury intoxication. Fish consumption more than twice per week and tooth-filling of mother more than five may increase mercury level. On the contrary, regular diet rich in vegetable decreases the mercury level.

  11. 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.

  12. Prediction of severe neonatal hyperbilirubinemia using cord blood hydrogen peroxide: a prospective study.

    Directory of Open Access Journals (Sweden)

    Hung-Chieh Chou

    Full Text Available BACKGROUND: We hypothesized that cord blood hydrogen peroxide (H2O2 could be utilized to predict the severity of neonatal hyperbilirubinemia. METHODS: We prospectively enrolled term or near-term healthy neonates. Cord blood and capillary blood at three days of age were measured for hydrogen peroxide and bilirubin concentrations. For newborns with hyperbilirubinemia, further blood samples were obtained at five and seven days of age. Newborns were divided into severe or less severe hyperbilirubinemic groups (peak bilirubin ≥17 mg/dL or not. The sensitivity, specificity, and negative predictive values were determined. RESULTS: There were 158 neonates enrolled. The incidence of neonatal hyperbilirubinemia was 30.5% for a concentration ≥15 mg/dl. The rising patterns were similar among bilirubin concentrations and hydrogen peroxide levels during the first few days of life. There was a strong positive correlation between bilirubin concentrations and hydrogen peroxide levels after correlation analysis. The rate of severe hyperbilirubinemia was 13.3%. It revealed that a cord blood hydrogen peroxide signal level of 2500 counts/10 seconds was an appropriate cut-off for predicting severe hyperbilirubinemia. Sensitivity and the negative predictive value were 76.2% and 93.3%, respectively. CONCLUSIONS: Our findings confirm that hydrogen peroxide levels and bilirubin concentrations in cord and neonatal blood are closely related. A cord blood hydrogen peroxide level above 2500 counts/10 seconds associated with a high predictive value for severe hyperbilirubinemia. This method provides information about which neonate should be closely followed after discharge from the nursery.

  13. Prenatal exposure to lead in Spain: cord blood levels and associated factors.

    Science.gov (United States)

    Llop, Sabrina; Aguinagalde, Xabier; Vioque, Jesus; Ibarluzea, Jesús; Guxens, Mònica; Casas, Maribel; Murcia, Mario; Ruiz, María; Amurrio, Ascensión; Rebagliato, Marisa; Marina, Loreto Santa; Fernandez-Somoano, Ana; Tardon, Adonina; Ballester, Ferran

    2011-05-01

    Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. ≥ vs < 2μg/dL). A low percentage of cord blood samples with lead levels ≥ 2μg/dL were found (5.9%). Geometric mean and maximum were 1.06μg/dL and 19μg/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels ≥ 2μg/dL. In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Homing of circulating blood endothelial progenitor cells after myocardial infarction is mediated by Akt-SDF-1-signal pathway

    Institute of Scientific and Technical Information of China (English)

    赵岚

    2013-01-01

    Objective To investigate the expressions of protein kinase B(Akt) and stromal cell-derived factor-1(SDF-1) and their relations with circulating blood endothelial progenitor cell homing after myocardial infarction(MI). Methods MI was induced in the

  15. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

  16. Early umbilical cord clamping contributes to elevated blood lead levels among infants with higher lead exposure.

    Science.gov (United States)

    Chaparro, Camila M; Fornes, Raymond; Neufeld, Lynnette M; Tena Alavez, Gilberto; Eguía-Líz Cedillo, Raúl; Dewey, Kathryn G

    2007-11-01

    To investigate whether infant iron status, modified by umbilical cord clamping time and infant feeding mode, affected infant blood lead concentration at 6 months of age. Participants were a subset of women and their infants randomized to receive early (10 seconds) or delayed (2 minutes) umbilical cord clamping and were monitored to 6 months postpartum in Mexico City. Iron and lead status was analyzed in maternal, placental, and 6-month infant blood samples. Baseline maternal lead exposure data and infant feeding data at 2, 4, and 6 months were collected. In the total sample, maternal blood lead concentration, infant ferritin, and breast-feeding practices predicted infant blood lead concentration. Among infants with higher placental blood lead concentration and breast-fed infants not receiving any iron-fortified formula or milk at 6 months, early clamping increased infant blood lead concentration, an effect mediated in part via decreased infant iron status. Early cord clamping, by decreasing infant iron status, contributes to higher blood lead concentrations at 6 months of age among infants at high risk.

  17. Inflammatory Markers in Umbilical Cord Blood from Small-For-Gestational-Age Newborns

    DEFF Research Database (Denmark)

    Lausten-Thomsen, Ulrik; Greisen, Gorm; Olsen, Marianne;

    2014-01-01

    This study investigates the role of inflammation in intrauterine growth retardation by exploring the levels of inflammatory markers in umbilical cord blood from neonates who were born small-for-gestational-age (SGA) and comparing them to neonates who were born appropriate-for-gestational-age (AGA...... of elevated inflammatory markers in the cord blood from SGA infants compared to AGA infants, and consequently the results suggest an inflammatory component in intrauterine growth restriction (IUGR).......This study investigates the role of inflammation in intrauterine growth retardation by exploring the levels of inflammatory markers in umbilical cord blood from neonates who were born small-for-gestational-age (SGA) and comparing them to neonates who were born appropriate-for-gestational-age (AGA......-eclampsia were excluded. SGA was defined as two standard derivations below the expected for term and gender. In multivariate regression analyses significant elevation in cord blood concentration of IL-6 was demonstrated in the SGA group (mean 4.56 vs. 2.38, p = 0.002). The results indicate the presence...

  18. Individualized conditioning regimes in cord blood transplantation : Towards improved and predictable safety and efficacy

    NARCIS (Netherlands)

    Admiraal, R; Boelens, J J

    INTRODUCTION: The conditioning regimen used in cord blood transplantation (CBT) may significantly impact the outcomes. Variable pharmacokinetics (PK) of drugs used may further influence outcome. Individualized dosing takes inter-patient differences in PK into account, tailoring drug dose for each

  19. Cord blood dendritic cell subsets in African newborns exposed to Plasmodium falciparum in utero.

    NARCIS (Netherlands)

    Breitling, L.P.; Fendel, R.; Mordmueller, B.; Adegnika, A.A.; Kremsner, P.G.; Luty, A.J.F.

    2006-01-01

    Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring o

  20. A report of high triglyceride level in cord blood of Iranian newborns

    Directory of Open Access Journals (Sweden)

    Seyed Ali Naghi Kazemi

    2013-01-01

    Conclusion: The mean and 95 th percentiles of triglyceride levels in cord blood of our newborn infants were higher than other reports. We recommend that larger studies should be conducted in this area to establish preventive ways for increasing epidemic of the metabolic syndrome.

  1. Serum selenium concentration in maternal and umbilical cord blood. Relation to course and outcome of pregnancy

    DEFF Research Database (Denmark)

    Bro, S; Berendtsen, H; Nørgaard, J

    1988-01-01

    complications and selenium values. In mothers with uncomplicated pregnancies and deliveries serum selenium concentrations were 0.84 +/- 0.19 mumol/l (mean +/- SD), whereas in cord blood from full-term babies born adequate for gestational age and with no malformations serum selenium concentrations were 0...

  2. Immunitary bioeconomy: the economisation of life in the international cord blood market.

    Science.gov (United States)

    Brown, Nik; Machin, Laura; McLeod, Danae

    2011-04-01

    This paper examines an emerging bioeconomy centred on the international banking and trade in cord blood. Since the late 1980s cord blood has been used in an expanding range of treatments and as an alternative to the use of bone marrow stem cells. This is particularly the case in treating ethnic minority populations who have historically been under-represented in bone marrow registries. The paper explores the mobilisation and commercialisation of an increasingly important bioeconomic resource with cord blood units trading internationally at high prices. This is a market mediated through a sophisticated global network of immunologically typed and matched bodily matter in which immunity has become a form of 'corporeal currency'. Based on recent international figures we reflect upon the balance of trade between imports and exports across the world's cord blood bioeconomy. Theoretically, this case is, we suggest, an extension of what Roberto Esposito (2008) has termed an 'immunitary paradigm' in which immunity has become the basis for new forms of bioeconomic flow, circulation and exchange. Esposito (2008). Bios: Biopolitics and Philosophy. Minnesota, MN: University of Minnesota Press. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Adipokines in umbilical cord blood from children born large for gestational age

    DEFF Research Database (Denmark)

    Lausten-Thomsen, Ulrik; Christiansen, Michael; Hedley, Paula Louise

    2016-01-01

    of adipokines and their mutual relationship at birth in children born to non-diabetic mothers. METHODS: Adiponectin, leptin and sOB-R were measured using ELISA-based commercial kits in umbilical cord blood from 60 neonates (30 born large for gestational age [LGA] and 30 born appropriate for gestational age [AGA...

  4. Design guidelines for an umbilical cord blood stem cell therapy quality assessment model

    Science.gov (United States)

    Januszewski, Witold S.; Michałek, Krzysztof; Yagensky, Oleksandr; Wardzińska, Marta

    The paper enlists the pivotal guidelines for producing an empirical umbilical cord blood stem cell therapy quality assessment model. The methodology adapted was single equation linear model with domain knowledge derived from MEDAFAR classification. The resulting model is ready for therapeutical application.

  5. Sex-Specific Associations between Umbilical Cord Blood Testosterone Levels and Language Delay in Early Childhood

    Science.gov (United States)

    Whitehouse, Andrew J. O.; Mattes, Eugen; Maybery, Murray T.; Sawyer, Michael G.; Jacoby, Peter; Keelan, Jeffrey A.; Hickey, Martha

    2012-01-01

    Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time-points. Methods: Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When…

  6. Maternal and Cord Blood Hepcidin Concentrations in Severe Iron Deficiency Anemia

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    Sriparna Basu

    2016-10-01

    Conclusion: Even in the presence of low serum iron and ferritin, maternal and cord blood hepcidin concentrations remained high in severe anemia. Failure of this proportional suppression of hepcidin indicates poor systemic bioavailability of iron to the mother and poor placental transport.

  7. Individualized conditioning regimes in cord blood transplantation : Towards improved and predictable safety and efficacy

    NARCIS (Netherlands)

    Admiraal, R; Boelens, J J

    2016-01-01

    INTRODUCTION: The conditioning regimen used in cord blood transplantation (CBT) may significantly impact the outcomes. Variable pharmacokinetics (PK) of drugs used may further influence outcome. Individualized dosing takes inter-patient differences in PK into account, tailoring drug dose for each in

  8. Fat-soluble vitamins in cord blood and colostrum in the south of China.

    Science.gov (United States)

    Tamai, H; Mingci, Z; Kawamura, N; Kuno, T; Ogihara, T; Mino, M

    1996-01-01

    Certain diseases have been associated with micronutrient deficiencies in China, and nutritional assessments have become important means of preventing such diseases. In the present study, fat-soluble vitamins including vitamins A, D, E, K, and beta-carotene in the cord blood and colostrum of Chinese subjects in Guilin, China, were assayed and compared with those of Japanese subjects in Osaka, Japan. These vitamins were analyzed by high-performance liquid chromatography. Vitamin A and E levels in the cord blood and colostrum of the Chinese group showed almost the same values as those of the Japanese group. There was also no significant difference in vitamin D level in cord blood between the two groups, while significantly lower levels of beta-carotene and cryptoxanthin, and a higher level of PIVKA-II (protein induced in vitamin K absence) in cord blood were observed in the Chinese group. These findings pointed to a restricted intake of green-yellow vegetables in the Chinese group and an increased risk of hemorrhagic disease in newborn of that group is suggested.

  9. Increased blood pressure can reduce fatigue of thenar muscles paralyzed after spinal cord injury

    NARCIS (Netherlands)

    Butler, JE; Ribot-Ciscar, E; Zijdewind, Inge; Thomas, CK

    The aim of this study was to evaluate whether increases in blood pressure, and presumably muscle perfusion pressure, improve the endurance of thenar muscles paralyzed chronically by cervical spinal cord injury (SCI). Resting mean arterial pressure (MAP) was low in all eight subjects (64 +/- 2 mmHg).

  10. Umbilical cord blood units for public storage donors screening for markers of infectious agents

    Directory of Open Access Journals (Sweden)

    A. B. Smolyaninov

    2012-01-01

    Full Text Available The screening of 3515 cord blood samples which had entered bank for public use for presence of markers of infectious agents was carried out. It was established that majority of cord blood units contain markers of cytomegalovirus and Toxoplasma (81% that is not a contraindication for storage and subsequent use of these samples. In 4.6% of cases umbilical cord blood units were subjected to disposal because of identification of viral hepatitis B and C, as well as Tr. pallidum markers, moreover, the largest share of the discarded units contained antibodies to HbscorAg – 71,3%. Inclusion of analysis on the presence of Anti-HBcor in the required laboratory screening of mothers-donors CB was proposed in order to reduce the percentage of discarded umbilical cord blood units for the public inventory.

  11. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood.

    Science.gov (United States)

    Zeddou, Mustapha; Briquet, Alexandra; Relic, Biserka; Josse, Claire; Malaise, Michel G; Gothot, André; Lechanteur, Chantal; Beguin, Yves

    2010-07-01

    Many studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these cells can be isolated are still under discussion. Whereas BM (bone marrow) is presented as the main source of MSC, despite the invasive procedure related to this source, the possibility of isolating sufficient numbers of these cells from UCB (umbilical cord blood) remains controversial. Here, we present the results of experiments aimed at isolating MSC from UCB, BM and UCM (umbilical cord matrix) using different methods of isolation and various culture media that summarize the main procedures and criteria reported in the literature. Whereas isolation of MSC were successful from BM (10:10) and (UCM) (8:8), only one cord blood sample (1:15) gave rise to MSC using various culture media [DMEM (Dulbecco's modified Eagle's medium) +5% platelet lysate, DMEM+10% FBS (fetal bovine serum), DMEM+10% human UCB serum, MSCGM] and different isolation methods [plastic adherence of total MNC (mononuclear cells), CD3+/CD19+/CD14+/CD38+-depleted MNC and CD133+- or LNGFR+-enriched MNC]. MSC from UCM and BM were able to differentiate into adipocytes, osteocytes and hepatocytes. The expansion potential was highest for MSC from UCM. The two cell populations had CD90+/CD73+/CD105+ phenotype with the additional expression of SSEA4 and LNGFR for BM MSC. These results clearly exclude UCB from the list of MSC sources for clinical use and propose instead UCM as a rich, non-invasive and abundant source of MSC.

  12. Tissue perfusion in neonates undergoing open-heart surgery using autologous umbilical cord blood or donor blood components.

    Science.gov (United States)

    Chasovskyi, K; Fedevych, O; McMullan, D M; Mykychak, Y; Vorobiova, G; Zhovnir, V; Yemets, I

    2015-09-01

    This study evaluates the hemoglobin-oxygen relationship and tissue perfusion during cardiopulmonary bypass (CPB) in neonates undergoing open-heart surgery using autologous umbilical cord blood or donor blood components. We compared perioperative hematocrit (Hct), fetal hemoglobin (HbF), p(50)O(2), pH, pCO(2), serum lactate, duration of mechanical ventilation and intensive care unit (ICU) length of stay in neonates undergoing open-heart surgery using autologous umbilical cord blood (Group I, N=45) or donor blood components (Group II, N=65). The groups were similar with respect to diagnosis, weight, type of procedure, duration of CPB and duration of myocardial ischemia. Mean p(50)O(2) was significantly lower in Group I during CPB (19.7 vs. 22.3 mmHg, p=0.004) and at the end of CPB (20.1 vs. 22.8 mmHg, p=0.003). Median peak lactate during CPB was higher in Group I (4.8 vs. 2.2 mmol/l, pblood, tissue oxygen delivery appears to be preserved in neonates who undergo open-heart surgery using autologous umbilical cord blood. © The Author(s) 2014.

  13. Effect of anti-CD52 antibody alemtuzumab on ex-vivo culture of umbilical cord blood stem cells

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    Law Ping

    2008-10-01

    Full Text Available Abstract Background Excessive maturation of hematopoietic cells leads to a reduction of long-term proliferative capability during cord blood (CB expansion. In this study, we report the effects of anit-CD52 (Alemtuzumab, Campath on both short- and long-term ex vivo expansion of CB hematopoietic stem cells (HSC by evaluating the potential role of Alemtuzumab in preserving the repopulating capability in CB HSC and nonlymphoid progenitors. Methods Ex vivo expansion experiments were carried out using freshly purified CB CD34+ cells in StemSpan™ SFEM medium in the presence of stem cell factor, Flt3-Ligand and thrombopoietin at 50 ng/ml. Alemtuzumab (10 μg/ml was used to deplete CD52+ cells during the cultures. Flow cytometry was used to monitor CB HSC and their differentiation. Colony forming unit (CFU assays and long term culture-initiating cell (LTC-IC assays were performed on cells obtained from day 0 (before culture and day 14 after cultures. Secondary cultures was performed using CD34+ cells isolated at 35 days from primary cultures and further cultured in StemSpan™ SFEM medium for another 14 days to confirm the long term effect of alemtuzumab in liquid cultures. Results Compared to cytokines alone, addition of alemtuzumab resulted in a significant increase in total nucleated cells, absolute CD34+ cells, myeloid and megakaryocytic progenitors, multi-lineage and myeloid CFU and LTC-IC. Conclusion The results from current study suggested that the use of alemtuzumab for ex vivo expansion of CBHSC maybe advantageous. Our findings may improve current technologies for CBHSC expansion and increase the availability of CB units for transplantation. However, in vivo studies using animal models are likely needed in further studies to test the hematopoietic effects using such expanded CB products.

  14. Pertussis seroprevalence in adults, post-partum women and umbilical cord blood.

    Science.gov (United States)

    Fallo, Aurelia; Manonelles, Gabriela; Hozbor, Daniela; Lara, Claudia; Huespe, Miguel; Mazzeo, Silvina; Canle, Oscar; Galas, Marcelo; López, Eduardo

    2014-08-01

    Pertussis is a vaccine-preventable disease that affects people of all ages. Young adults who have lost their immunity to pertussis are the major source of infection in infants. Given the steady increase of pertussis cases, new prevention strategies are required. Objective. To assess pertussis seroprevalence in adult blood donors, post-partum women, and umbilical cords. Metod. Measurement of total titers of anti-Bordetella spp. (Bordetella) antibodies using an enzyme-linked immunosorbent assay. Serum samples from 103 donors, 101 post-partum women and 100 umbilical cords were analyzed. Titers <80 were considered of low impact against the disease. The assessment included transplacental transfer of antibodies and the umbilical cord/maternal ratio of antibody titers. Results. Donors mean age was: 28 ± 6 years old. Mediananti-Bordetella titers: 320; interquartile range (IQR):160-320; 10% had titers <80. Post-partum women mean age was: 26 ± 6 years old. Median anti-Bordetella titers:160 (IQR:80-320), with titers significantly lower than in female donors (p= 0.00002). Titers <80 were found in 30% of post-partum women. Median anti-Bordetella titers in umbilical cords: 160 (IQR: 80-160). Titers <80 were more frequently found in umbilical cords than in mothers (44% versus 30%, p= 0.04). Transplacental transfer was 0.83. Umbilical cord titers were equal to maternal titers in 54% of cases, lower in 37%, and higher only in 8%. Conclusion. Titers of anti-Bordetella antibodies in post-partum women were significantly lower than in female blood donors. Titers <80 were found in 30% of post-partum women and 44% of umbilical cords. These data may account for the high rates of pertussis in young infants who have not yet completed their vaccination schedule.

  15. 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

  16. 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

  17. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells.

    Science.gov (United States)

    Hiwarkar, Prashant; Qasim, Waseem; Ricciardelli, Ida; Gilmour, Kimberly; Quezada, Sergio; Saudemont, Aurore; Amrolia, Persis; Veys, Paul

    2015-12-24

    Unrelated cord blood transplantation (CBT) without in vivo T-cell depletion is increasingly used to treat high-risk hematologic malignancies. Following T-replete CBT, naïve CB T cells undergo rapid peripheral expansion with memory-effector differentiation. Emerging data suggest that unrelated CBT, particularly in the context of HLA mismatch and a T-replete graft, may reduce leukemic relapse. To study the role of CB T cells in mediating graft-versus-tumor responses and dissect the underlying immune mechanisms for this, we compared the ability of HLA-mismatched CB and adult peripheral blood (PB) T cells to eliminate Epstein-Barr virus (EBV)-driven human B-cell lymphoma in a xenogeneic NOD/SCID/IL2rg(null) mouse model. CB T cells mediated enhanced tumor rejection compared with equal numbers of PB T cells, leading to improved survival in the CB group (P cells that were autologous vs allogeneic to the lymphoma demonstrated that this antitumor effect was mediated by alloreactive rather than EBV-specific T cells. Analysis of tumor-infiltrating lymphocytes demonstrated that CB T cells mediated this enhanced antitumor effect by rapid infiltration of the tumor with CCR7(+)CD8(+) T cells and prompt induction of cytotoxic CD8(+) and CD4(+) T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies.

  18. FEASIBILITY OF COLLECTING UMBILICAL CORD BLOOD IN JORDAN AND THE EFFECT OF MATERNAL AND NEONATAL FACTORS ON HEMATOPOIETIC STEM CELL CONTENT

    Directory of Open Access Journals (Sweden)

    Ayad Ahmed Hussein

    2014-02-01

    Conclusion: We conclude that it is feasible to collect cord blood units in Jordan with excellent TNC and CD34+ cell content. The volume of cord blood collected was associated with higher TNC count and CD34+ count. Efforts toward establishing public cord blood banks in our area are warranted.

  19. Erythropoietic Potential of CD34+ Hematopoietic Stem Cells from Human Cord Blood and G-CSF-Mobilized Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Honglian Jin

    2014-01-01

    Full Text Available Red blood cell (RBC supply for transfusion has been severely constrained by the limited availability of donor blood and the emergence of infection and contamination issues. Alternatively, hematopoietic stem cells (HSCs from human organs have been increasingly considered as safe and effective blood source. Several methods have been studied to obtain mature RBCs from CD34+ hematopoietic stem cells via in vitro culture. Among them, human cord blood (CB and granulocyte colony-stimulating factor-mobilized adult peripheral blood (mPB are common adult stem cells used for allogeneic transplantation. Our present study focuses on comparing CB- and mPB-derived stem cells in differentiation from CD34+ cells into mature RBCs. By using CD34+ cells from cord blood and G-CSF mobilized peripheral blood, we showed in vitro RBC generation of artificial red blood cells. Our results demonstrate that CB- and mPB-derived CD34+ hematopoietic stem cells have similar characteristics when cultured under the same conditions, but differ considerably with respect to expression levels of various genes and hemoglobin development. This study is the first to compare the characteristics of CB- and mPB-derived erythrocytes. The results support the idea that CB and mPB, despite some similarities, possess different erythropoietic potentials in in vitro culture systems.

  20. Impairment of T-regulatory cells in cord blood of atopic mothers.

    Science.gov (United States)

    Schaub, Bianca; Liu, Jing; Höppler, Sabine; Haug, Severine; Sattler, Christine; Lluis, Anna; Illi, Sabina; von Mutius, Erika

    2008-06-01

    Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation. We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers. Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion. Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+)high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion. In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.

  1. Molecular characterization of microbial contaminants isolated from Umbilical Cord Blood Units for transplant

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    Juan Manuel Bello-López

    2015-12-01

    Full Text Available ABSTRACT Disposal of Umbilical Cord Blood Units due to microbial contamination is a major problem in Cord Blood Banks worldwide as it reduces the number of units available for transplantation. Additionally, economic losses are generated as result of resources and infrastructure used to obtain such units. Umbilical Cord Blood Units that showed initial microbial contamination were subject to strains isolation, identification, and characterization by sequencing the 16S rRNA gene and Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR. Moreover, tests of antimicrobial resistance/sensitivity and phenotypic activities that may play an important role in microbial infection were performed. Microbial contamination was detected in 120 Umbilical Cord Blood Units (2.31% in the period from 2003 to 2013. The most frequently isolated strains were Enterococcus faecium, followed by Staphylococcus epidermidis, Escherichia coli, Enterococcus faecalis, Staphylococcus haemoliticus, Klebsiella pneumoniae, Enterococcus durans, Lactobacillus helveticus, Enterococcus hiriae and Roseomonas genomospecies 5. The ERIC-PCR assays revealed a wide genetic diversity in some strains although belonging to the same genus and specie, indicating different sources of contamination. Broad-spectrum penicillins, third generation cephalosporins, aminoglycosides, and fluoroquinolones showed lower inhibitory activity on the tested strains. All strains were proteolytic, 67.69% were amylase-positive, 27.6% hemolysis-positive, and 34.71% nuclease-positive. The most common sources of contamination were: vaginal flora, digestive tract, and skin flora, highlighting the need for staff training in good manufacturing practices in collection SCU since all contaminants identified are part of the microbial flora of the donors. Implications and consequences in the therapeutic use of Umbilical Cord Blood Units for transplantation contaminated by multiresistant bacteria in immunocompromised

  2. Differentiation of smooth muscle progenitor cells in peripheral blood and its application in tissue engineered blood vessels

    Institute of Scientific and Technical Information of China (English)

    Shang-zhe XIE; Ning-tao FANG; Shui LIU; Ping ZHOU; Yi ZHANG; Song-mei WANG; Hong-yang GAO; Luan-feng PAN

    2008-01-01

    Background: A major shortcoming in tissue engineered blood vessels (TEBVs) is the lack of healthy and easily attainable smooth muscle cells (SMCs). Smooth muscle progenitor cells (SPCs), especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods: SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV (EGM-2-MV) medium containing platelet-derived growth factor-BB (PDGF BB). Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell (SOC) phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction (RT-PCR). The cells were seeded onto the silk fibroin-modified poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SF-PHBHHx) scaffolds by 6×104 cells/cm'2 and cultured under the static con-dition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay, scanning electron microscope (SEM), and 4,6-diamidino-2-phenylindole (DAPI) staining. Results: SOCs displayed specific "hill and valley" morphology, expressed the specific markers of the SMC lineage: protein, and extracellular matrix components elastin and matrix Gla protein (MGP), as well as vascular endothelial growth factor (VEGF). After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion: SPCs isolated from peripheral blood can be differentiated into the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell source for constructing TEBVs.

  3. Antitumor activities of human dendritic cells derived from peripheral and cord blood

    Institute of Scientific and Technical Information of China (English)

    Jin-Kun Zhang; Jun Li; Hai-Bin Chen; Jin-Lun Sun; Yao-Juan Qu; Juan-Juan Lu

    2002-01-01

    AIM: To observe the biological specialization of humanperipheral blood dendritic cells (DC) and cord blood derivedDC and its effects on effector cells killing humanhepatocarcinoma cell line BEL-7402 in vitro.METHODS: The DC biological characteristics were detectedwith immunohistochemical and MTT assay. Two antitumorexperimental groups are: peripheral blood DC and cordblood DC groups. Peripheral blood DC groups used LAKcells as the effector cells and BEL-7402 as target cells, whilecord blood DC groups used CTL induced by tumor antigentwice pulsed DC as effector cells and BEL-7402 as targetcells, additional peripheral blood DC and cord blood DC areadded to observe its stimulating activities to effector cells.The effector's cytotoxicity to tumor cells were detected withneutral red colorimetric assay at two effector/target ratios of5:1 and 10: 1.RESULTS: Peripheral blood DC and cord blood DC highlyexpressed HLA-ABC, HLA-DR, HLA-DQ, CD54 and S-100protein. The stimulating activities to lymphocyteproliferation were compared between experimental groups(DC added) and control group (no DC added). In sixexperiment subgroups, the DC/lymphocyte ratio wassequentially 0.25: 100, 0.5: 100, 1: 100, 2: 100, 4: 100 and 8:100, A values(x± s) were 0.75396± 0.009, 0.84916± 0.010,0.90894± 0.012, 0.98371 ± 0.007, 1.01299 ± 0.006 and 1.20384± 0.006 in peripheral blood DC groups and 0.77650 ± 0.005,0.83008± 0.007, 0.92725 ± 0.007, 1.05990 ± 0.010, 1.15583 ±0.011, 1.22983 ± 0.011 in cord blood DC groups. A value was0.59517 ± 0.005 in control group. The stimulating activitieswere higher in experimental groups than in control group ( P< 0.01 ), which were increased when the DC concentrationwas enlarged ( P < 0.01 ). Two differently derived DCs hadthe same phenotypes and similar stimulating activities ( P >0.05). In peripheral blood DC groups, the cytotoxicity (x ±s) of the LD groups (experimental groups) and L groups(control group) was 58.16% ± 2.03% (5: 1), 46.18% ±2

  4. Association of prenatal antibiotics with foetal size and cord blood leptin and adiponectin.

    Science.gov (United States)

    Mueller, N T; Rifas-Shiman, S L; Blaser, M J; Gillman, M W; Hivert, M-F

    2017-04-01

    Early postnatal antibiotic use has been shown to promote excess weight gain, but it is unclear whether intrauterine exposure to antibiotics is associated with foetal growth and adiposity. The objective of this study was to examine associations of antibiotic prescription in each trimester of pregnancy with foetal size and adipokine levels at birth. In 2128 pregnant women from the pre-birth Project Viva cohort, from electronic medical records, we estimated antibiotic prescribing by timing during pregnancy. Outcomes were sex-specific birth weight-for-gestational-age z-score (BW/GA-z) and levels of umbilical cord leptin and adiponectin. We used linear regression models adjusted for maternal age, pre-pregnancy body mass index, parity, race/ethnicity, education, smoking during pregnancy, household income and child sex and additionally adjusted cord blood leptin and adiponectin models for gestation length. Of the 2128 women in our sample, 643 (30.2%) were prescribed with oral antibiotics during pregnancy. Mean (standard deviation) BW/GA-z was 0.17 (0.97), cord blood leptin was 9.0 ng mL(-1) (6.6) and cord blood adiponectin was 28.8 ng mL(-1) (6.8). Overall, antibiotic prescription in pregnancy was associated with lower BW/GA-z [multivariable adjusted β -0.11; 95% confidence interval {CI} -0.20, -0.01]. In trimester-specific analyses, only second trimester antibiotic prescription was associated with lower BW/GA-z (β -0.23; 95% CI -0.37, -0.08). Overall, antibiotic prescription in pregnancy was not associated with cord blood leptin or adiponectin levels. However, in trimester-specific analyses, third trimester antibiotic prescription was associated with higher cord blood leptin (β 2.28 ng mL(-1) ; 95% CI 0.38, 4.17). Antibiotics in mid-pregnancy were associated with lower birth weight for gestational age, whereas third trimester antibiotics were associated with higher cord blood leptin. © 2016 World Obesity Federation.

  5. Collection of peripheral progenitor cells: a comparison between Amicus and Cobe-Spectra blood cell separators.

    Science.gov (United States)

    Adorno, Gaspare; Del Proposto, Gianpaolo; Palombi, Francesca; Bruno, Antonio; Ballatore, Giovanna; Postorino, Massimiliano; Tendas, Andrea; Del Poeta, Giovanni; Isacchi, Giancarlo; Amadori, Sergio

    2004-04-01

    The authors compared the efficiency of two different blood cell separators (Amicus and Cobe-Spectra) in collecting peripheral blood progenitor cells for autologous or homologous transplantation. A total number of 129 procedures were performed, 36 with Spectra, 93 with Amicus. There was no difference between Spectra and Amicus efficiencies for CD34+ cell collection (46.685% vs 46.235%; p=n.s) but the platelet efficiencies were 17.31% and 12.54% respectively (p=0.04) and, if autologous and allogeneic collections were considered separately, a marked difference resulted in allogeneic platelet efficiency between 6 Spectra and 23 Amicus procedures (26.83% vs 8.68%, p=0.0004). The authors were able to demonstrate that in 70 Amicus autologous collections there was a different platelet efficiency, if peripheral count was considered: 12 procedures performed with a platelet count > 100 x 10(9)/l had a very low efficiency (6.86%), but this value increased if platelet count lowered (13.02% if between 100 and 50 x 10(9)/l, 22.63% if between 50 and 0 x 10(9)/l, 23 and 35 procedures respectively). The study is preliminary and the number of collections is little, but the overall data suggest that Spectra (AutoPBSC, V 6.0) and Amicus separators have the same efficiency for collecting CD34+ cells while Amicus procedures have a very low platelet contamination, especially with donors.

  6. Stem cells from umbilical cord blood do have myogenic potential, with and without differentiation induction in vitro

    Directory of Open Access Journals (Sweden)

    Gollop Thomaz R

    2009-01-01

    Full Text Available Abstract The dystrophin gene, located at Xp21, codifies dystrophin, which is part of a protein complex responsible for the membrane stability of muscle cells. Its absence on muscle causes Duchenne Muscular Dystrophy (DMD, a severe disorder, while a defect of muscle dystrophin causes Becker Muscular Dystrophy (DMB, a milder disease. The replacement of the defective muscle through stem cells transplantation is a possible future treatment for these patients. Our objective was to analyze the potential of CD34+ stem cells from umbilical cord blood to differentiate in muscle cells and express dystrophin, in vitro. Protein expression was analyzed by Immunofluorescence, Western Blotting (WB and Reverse Transcriptase – Polymerase Chain Reaction (RT-PCR. CD34+ stem cells and myoblasts from a DMD affected patient started to fuse with muscle cells immediately after co-cultures establishment. Differentiation in mature myotubes was observed after 15 days and dystrophin-positive regions were detected through Immunofluorescence analysis. However, WB or RT-PCR analysis did not detect the presence of normal dystrophin in co-cultures of CD34+ and DMD or DMB affected patients' muscle cells. In contrast, some CD34+ stem cells differentiated in dystrophin producers' muscle cells, what was observed by WB, reinforcing that this progenitor cell has the potential to originate muscle dystrophin in vitro, and not just in vivo like reported before.

  7. Isolation and characterization of in vitro culture of hair follicle cells differentiated from umbilical cord blood mesenchymal stem cells.

    Science.gov (United States)

    Bu, Zhang-Yu; Wu, Li-Min; Yu, Xiao-Hong; Zhong, Jian-Bo; Yang, Ping; Chen, Jian

    2017-07-01

    The present investigation explored the in vitro culture, isolation and characterization of hair follicle cell differentiation from umbilical cord blood mesenchymal stem cells (MSCs). Flow cytometry was used to obtain MSCs from the isolation and purification of human umbilical cord blood MSCs. Culture suspension of hair follicle organ was centrifuged and the supernatant used in the culture medium of MSCs, and the entire process of induced differentiation was recorded by photomicroscopy. The expression level of surface marker CK15 of hair follicle cells obtained from induced differentiation was detected with immunofluorescence. RT-PCR method was used to further detect the difference in expression of CK15 between hair follicle cells and umbilical cord blood MSCs, and statistical analysis was carried out. CD44(+)CD29(+) double-labeled cells accounted for 50.8% of all the samples of umbilical cord blood MSCs in this study. The diameter of hair follicle cells differentiated from umbilical cord blood stem cells reached 800×10(-3) mm after 3 weeks of cell culture. Based on the detection and colocalization of CK15 expression in induced hair follicle cells, the overlap ratio between CK15 and nuclei reached 83% in hair follicle cells, which was obviously higher than that in umbilical cord blood stem cells. The difference had statistical significance (Pumbilical cord blood stem cells by using the supernatant from hair follicle cells. This method can be used for high-speed induced differentiation with high purity, which is promising for clinical application.

  8. Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

    Directory of Open Access Journals (Sweden)

    Anahita Mohammadian

    2017-04-01

    Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

  9. Long-Term Quality Control Program Plan for Cord Blood Banks in Korea: A Pilot Study for Cryopreservation Stability.

    Science.gov (United States)

    Seo, Soo Hyun; Shin, Sue; Roh, Eun Youn; Song, Eun Young; Oh, Sohee; Kim, Byoung Jae; Yoon, Jong Hyun

    2017-03-01

    Maintaining the quality of cryopreserved cord blood is crucial. In this pilot study, we describe the results of the internal quality control program for a cord blood bank thus far. Donated cord blood units unsuitable for transplantation were selected for internal quality control once a month. One unit of cord blood, aliquoted into 21 capillaries, was cryopreserved and thawed annually to analyze the total nucleated cell count, CD34⁺ cell count, cell viability test, and colony-forming units assay. No significant differences in the variables (total nucleated cell count, cell viability, CD34⁺ cell count) were observed between samples cryopreserved for one and two years. Upon comparing the variables before cryopreservation and post thawing with the capillaries of one year of storage, cell viability and CD34⁺ cell counts decreased significantly. The use of cord blood samples in capillaries, which can be easily stored for a long period, was similar to the methods used for testing segments attached to the cord blood unit. The results of this study may be useful for determining the period during which the quality of cryopreserved cord blood units used for transplantation is maintained.

  10. In vitro differentiation of human umbilical cord blood mesenchymal ...

    African Journals Online (AJOL)

    May H. Hasan

    2016-08-05

    Aug 5, 2016 ... hepatocyte-like cells were detected on day 21 and increased on day 28. Protein ... MSCs can be a promising source of cell therapy for intractable liver diseases. ..... blood-derived mesenchymal stem cells by DNA microarray.

  11. Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial.

    Science.gov (United States)

    Andersson, Ola; Hellström-Westas, Lena; Andersson, Dan; Clausen, Jesper; Domellöf, Magnus

    2013-05-01

    To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling. Secondary analysis of a parallel-group, single-center, randomized controlled trial. Swedish county hospital. 382 term deliveries after a low-risk pregnancy. Deliveries were randomized to DCC (≥180 seconds, n = 193) or ECC (≤10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO2 . Main outcome measures. PPH and proportion of valid blood gas samples. The differences between the DCC and ECC groups with regard to PPH (1.2%, p = 0.8) and severe PPH (-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between the DCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC. Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  12. Cord blood banking - bio-objects on the borderlands between community and immunity.

    Science.gov (United States)

    Brown, Nik; Williams, Rosalind

    2015-01-01

    Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.

  13. Risk Factors and Options to Improve Engraftment in Unrelated Cord Blood Transplantation

    Directory of Open Access Journals (Sweden)

    Anna D. Petropoulou

    2011-01-01

    Full Text Available Use of umbilical unrelated cord-blood (UCB cells as an alternative source of hematopoietic cell transplantation has been widely used mainly for patients lacking an HLA-matched donor. UCB present many advantages over bone marrow or mobilized peripheral blood from volunteer donors, such as rapid availability, absence of risk for the donor, and decreased incidence of acute graft-versus-host disease. However, a significant clinical problem is delayed engraftment that is directly correlated with the number of hematopoietic stem cells in a cord-blood unit. The identification of prognostic factors associated with engraftment that can be easily modified (e.g., strategies for donor choice and the development of new approaches including use of multiple donors, intrabone injection of UCB, ex vivo expansion, and cotransplantation with accessory cells are of crucial importance in order to circumvent the problem of delayed engraftment after UCB transplantation. Those approaches may increase the quality and availability of UCB for transplantation.

  14. [Pooled Umbilical Cord Blood Plasma for Culturing UCMSC and Ex Vivo Expanding Umbilical Cord Blood CD34⁺ Cells].

    Science.gov (United States)

    Wu, Jie-Ying; Lu, Yan; Chen, Jin-Song; Wu, Shao-Qing; Tang, Xue-Wei; Li, Yan

    2015-08-01

    To investigate the feasibility of umbilical cord blood plasma (UCP) as a replacement for fetal bovine serum (FBS) for culturing mesenchymal stem cells (MSC) derived from umbilical cord, and to observe the supporting effects of these cells (served as a feeder layer) on ex vivo expanding of human umbilical cord blood CD34(+) cells. Umbilical cord blood (UCB) units were suitable if the Guangzhou cord blood bank donor selection criteria strictly were fulfilled. UCP were ready to use after the collection from the plasma depletion/reduction during the processing and pooling of suitable UCB units (at least 30 units were screened for pathogens and microorganisms, and qualified). Umbilical cord mesenchymal stem cells (UCMSC) were harvested from the umbilical cord tissue of health full-term newborns after delivery by enzyme digestion and divided into 3 groups: group 1 and 2 were cultured in the presence of DMEM/F12 containing either FBS or UCP; and group 3 was cultured in serum-free medium (StemPro® MSC SFM CTS™). Morphology, proliferation and surface marker expression were examined by flow cytometry, and the differentiation toward adipogenic and osteogenic lineages was used for investigating the effect of media on UCMSC after 3-5 passages. Next, the cells cultured in the three different media were cryopreserved and thawed, then prepared as feeder layers with the name of UCMSC(FBS), UCMSC(UCP), and UCMSC(SFM), respectively. The CD34⁺ cells were separated from UCB by magnetic activated cell sorting (MACS) and divided into 4 groups cultured in StemPro(-34) SFM medium added with hematopoietic cytokine combination (StemSpan® CC100). The control group included only CD34⁺ cells as group A (blank control) and experimental groups included UCMSC(FBS) + CD34⁺ cells as group B, UCMSC(UCP) + CD34⁺ cells as group C, UCMSC(SFM) + CD34⁺ cells as group D, and cells in all groups were cultured ex vivo for 7 days. The nucleated cell (NC) number was counted by cell counter, CD34

  15. Current status of cord blood banking during first two years of 'National Government-Assigned Public Cord Blood Banks Operation' in Korea.

    Science.gov (United States)

    Roh, Eun Youn; Lee, Jung Lim; Yoon, Jong Hyun; Kim, Su Yeon; Lee, Kyung Eun; Song, Do Young; Kim, Tai Gyu; Shin, Sue

    2014-10-01

    Cord blood (CB) has become a viable stem cell source for hematopoietic stem cell transplantation (HSCT), and public cord blood banks (CBBs) have been established to manage donated cord blood units (CBUs) for unrelated HSCT. As the potential uses for CB continue to grow, there is a global tendency to encourage public CBBs. The aim of this study was to investigate the current status of public CBBs that were designated and supported by the Korean national government. We analyzed 6,168 CBUs preserved at the 3 Government-Assigned Public CBBs during their first two years of operation (2012-2013) and the standard operating procedures for CB processing at each CBB. CBU inventories at ALLCORD, Catholic HSC Bank and Fatima Public CBB were 4,022, 1,207 and 939 units, respectively. Total nucleated cell (TNC) counts per unit were 11.0 × 10(8) at ALLCORD, 10.7 × 10(8) at Fatima and 9.8 × 10(8) at Catholic, and all far exceeded the requirement for cryopreservation under the law (7.0 × 10(8)). CD34(+) cell counts and % were as follows: 3.5 × 10(6) (0.31 %) in ALLCORD, 2.2 × 10(6) (0.20 %) in Fatima and 2.2 × 10(6) (0.22 %) in Catholic. All the three banks observed the 'CB Act' in dealing with CBUs, including collection, processing, laboratory tests and cryopreservation. Government supported and strictly law-abiding public CBBs in Korea have considerable CBU inventories of high quality in terms of efficacy and safety. Legislation and accompanying government-support will be helpful for establishing CB standardization, vitalizing CBT and improving clinical outcomes.

  16. [Correlation analysis of the pre-pregnant body mass index, the gestational weight gain and umbilical cord blood C peptide].

    Science.gov (United States)

    Chen, X L; Han, Y; Zhao, X M; Liu, Y; Lü, J J

    2017-01-03

    Objective: To explore the correlation among the pre-pregnant body mass index (BMI), gestational weight gain (GWG) and umbilical cord blood C peptide, and to investigate the influence of maternal weight management on the incidence of baby long-term metabolic syndrome. Methods: During May to Aug.2015, 485 pregnant women in Zhejiang Taizhou first people's hospital and Taizhou Huangyan maternal &child care service centre were selected in random and divided into four groups according to pre-pregnant BMI: low body mass, normal body mass, over body mass and obese group, and also divided into two groups for getting gestational diabetes mellitus (GDM) or not. According to the gestational weight gain (GWG), all the cases were divided into two groups: above the Institute Of Medicine (IMO) 2009 recommendations or not. According to the outcome, the GDM group which had received weight control treatment, was divided into successful treat group or not. At last, we tested the umbilical cord blood C peptide and birth weight of each newborn and compared the difference in all subgroups. The correlation between the umbilical cord blood C peptide and birth weight were analysed. Results: (1) In the pre-pregnant BMI groups, there were significant differences of incidence of GDM (P0.05). (2) Newborn birth weight and the umbilical cord blood C peptide were positively correlated (r=0.673, PUmbilical cord blood C peptide showed the correlation in all subgroups for different pre-pregnant BMI, GDM or not, overweight or not (Pumbilical cord blood C peptide, the GDM mostly (β=0.58), pre-pregnant BMI secondly (β: 0.36, 0.38) , and GWG weakly (β=0.17). (5) By stratification analysis, in GDM group, low body mass was negatively correlated with umbilical cord blood C peptide (Pumbilical cord blood C peptide (Pumbilical cord blood C peptide. Suitable maternal weight control especially pre-pregnant body mass index control will lower the baby long-term metabolic syndrome incidence.

  17. Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood.

    Science.gov (United States)

    Zhang, Qian; Wang, Lili; Luo, Chenghan; Shi, Zanyang; Cheng, Xinru; Zhang, Zhen; Yang, Yi; Zhang, Yi

    2014-11-01

    Cord blood has gradually become an important source for hematopoietic stem cell transplantation (HSCT) in the human, particularly in pediatric patients. Adoptive cellular immunotherapy of patients with hematologic malignancies after umbilical cord blood transplant is crucial. Cytokine‑induced killer (CIK) cells derived from cord blood are a new type of antitumor immune effector cells in tumor prevention and treatment and have increasingly attracted the attention of researchers. On the other hand, it has been suggested that preterm infant cord blood retains an early differentiation phenotype suitable for immunotherapy. Therefore, we determined the phenotypic and functional characterization of CIK cells derived from preterm infant cord blood (PCB-CIK) compared with CIK cells from term infant cord blood (TCB-CIK). Twenty cord blood samples were collected and classified into two groups based on gestational age. Cord blood mononuclear cells (CBMCs) were isolated, cultured and induced to CIK cells in vitro. We used flow cytometry to detect cell surface markers, FlowJo software to analyze the proliferation profile and intracellular staining to test the secretion of cytokines. Finally, we evaluated the antitumor activity of CIK cells against K562 in vitro. Compared with TCB-CIK, PCB-CIK cells demonstrated faster proliferation and higher expression of activated cell surface markers. The secretion of IL-10 was lower in PCB-CIK cells while the expression of perforin and CD107a had no significant difference between the two cell groups. PCB-CIK cells exhibited a high proliferation rate while the cytotoxic activity had no difference between the PCB-CIK and TCB-CIK cells. Hence preterm infant cord blood may be a potential source for immunotherapy.

  18. 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.

  19. 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.

  20. 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.

  1. Analysis of hemoglobin adducts from acrylamide, glycidamide, and ethylene oxide in paired mother/cord blood samples from Denmark

    DEFF Research Database (Denmark)

    von Stedingk, Hans; Vikström, Anna C; Rydberg, Per

    2011-01-01

    for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide......, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.......20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together...

  2. Impact of C-rel inhibition of cord blood-derived B-, T-, and NK cells.

    Science.gov (United States)

    Fallahi, Shirin; Mohammadi, Seyede Momeneh; Tayefi Nasrabadi, Hamid; Alihemmati, Alireza; Samadi, Naser; Gholami, Sanaz; Shanehbandi, Dariush; Nozad Charoudeh, Hojjatollah

    2017-12-01

    The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells. This particular source was selected as cord blood is an important source of cells used for transplantation and immunotherapy, primarily in treating leukemias. As stem cell factor (SCF) and FLT3 are important agents for hematopoietic stem cell expansion, and cytokines like interleukin (IL)-2, -7, and -15 are essential for T- and B- (and also NK) cell development and proliferation, the current study evaluated c-Rel expression in cord blood mononuclear cells and CD34(+ )cells, as well as effects on B-, T-, and NK cells associated with alterations in c-Rel expression, using flow cytometry and PCR. The results showed c-Rel expression increased among cells cultured in the presence of SCF and FLT3 but was reduced when IL-2, IL-7, and IL-15 were used all together. Further, inhibition of c-Rel expression by siRNA reduced cord blood-derived B-, T-, and NK cell differentiation and expansion. These results indicated that with cells isolated from cord blood, c-Rel has an important role in B-, T-, and NK cell differentiation and, further, that agents (select cytokines/growth factors) that could impact on its expression might not only affect immune cell profiles in a host but could potentially also limit apoptotic activities in (non-)immune cells in that host. In the context of cancer (immuno)therapy, in particular, when cord blood is used an important source in stem cell transplantation in

  3. Impact of maternal and neonatal factors on parameters of hematopoietic potential in umbilical cord blood

    Science.gov (United States)

    Al-Deghaither, Sara Y.

    2015-01-01

    Objectives: To determine characteristics of laboratory parameters of hematopoietic potential in umbilical cord blood and their association with maternal and neonatal factors. Methods: This prospective analysis was performed on 206 umbilical cord blood donations (50-200 ml) from King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia between January and September 2014. Samples were processed and analyzed for total nucleated cells (TNC’s), cluster designation (CD)45+, CD34+ counts, nucleated red blood cells (NRBCs) count, and viability testing. Results: Most of the study participants (63.6%) were on their first 3 deliveries and from women with age between 17 and 30 years (80.6%). The donated volume was 50.4-192.4 ml, TNCs ranged from 500.2×106 to 9430.3 ×106 cells, and CD34+ cells ranged from 1.25×106 to 12.82×106/unit. The volume was positively affected by bigger birth weight of the baby (pumbilical cord blood, several maternal and neonatal factors should be considered, as younger maternal age, neonatal birth weight >3300 grams, larger placental size, and first or second-born babies, were shown to be associated with higher TNCs, CD34+, CD45+, NRBCs, and viability. PMID:25987113

  4. Association between umbilical cord glucocorticoids and blood pressure at age 3 years

    Directory of Open Access Journals (Sweden)

    Rich-Edwards Janet W

    2008-08-01

    Full Text Available Abstract Background Animal data show that decreased activity of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2, which potently inactivates glucocorticoids (e.g. cortisol to inert forms (cortisone, allows increased access of maternal glucocorticoids to the fetus and 'programs' hypertension. Data in humans are limited. We examined in humans the association between venous umbilical cord blood glucocorticoids, a potential marker for placental 11β-HSD2 enzyme activity, and blood pressure at age 3 years. Methods Among 286 newborns in Project Viva, a prospective pre-birth cohort study based in eastern Massachusetts, we measured cortisol (F and cortisone (E in venous cord blood and used the ratio of F/E as a marker for placental 11β-HSD2 activity. We measured blood pressure (BP when the offspring reached age 3 years. Using mixed effects regression models to control for BP measurement conditions, maternal and child characteristics, we examined the association between the F/E ratio and child BP. Results At age 3 years, each unit increase in the F/E ratio was associated with a 1.6 mm Hg increase in systolic BP (95% CI 0.0 to 3.1. The F/E ratio was not associated with diastolic blood pressure or birth weight for gestational age z-score. Conclusion A higher F/E ratio in umbilical venous cord blood, likely reflecting reduced placental 11β-HSD2 activity, was associated with higher systolic blood pressure at age 3 years. Our data suggest that increased fetal exposure to active maternal glucocorticoids may program later systolic blood pressure.

  5. Cell-Associated Interleukin-8 in Cord Blood of Term and Preterm Infants

    Science.gov (United States)

    Dembinski, J.; Behrendt, D.; Heep, A.; Dorn, C.; Reinsberg, J.; Bartmann, P.

    2002-01-01

    To assess the effect of gestational age and labor on the interleukin-8 (IL-8) concentration in whole cord blood and serum, IL-8 levels were determined simultaneously in cord blood serum and lysate in 134 infants. Following the elimination of some of the samples due to exclusion criteria, the data for 99 uninfected infants (71 term and 28 preterm) and 9 infants with neonatal bacterial infection delivered either vaginally or by elective or emergency cesarean section were analyzed. The effects of labor and gestational age were tested by analysis of variance. IL-8 was not detectable in the serum of 25 infants, whereas IL-8 levels in whole blood were measurable in all of the samples. The median IL-8 conncentrations in whole cord blood lysate were 106 pg/ml (range, 20 to 415 pg/ml) in preterm infants and 176 pg/ml (range, 34 to 1,667 pg/ml) in term infants. In contrast to the IL-8 levels in serum, IL-8 levels in whole blood were reduced after ECS. Gestational age had no independent effect on the IL-8 concentrations in either serum or whole blood; these concentrations increased in infected infants after labor. We conclude that the neonatal proinflammatory response to labor stress was more evident in the concentrations of IL-8 in whole blood than in serum. The levels of IL-8 in whole-blood lysate reflect proinflammatory stimulation in neonates and may be a useful diagnostic tool for the early diagnosis of neonatal infection. PMID:11874870

  6. Determination of glycated and acetylated hemoglobins in cord blood by time-of-flight mass spectrometry.

    Science.gov (United States)

    Dupont, Félix O; Gagnon, René; Ardilouze, Jean-Luc; Auray-Blais, Christiane

    2011-07-01

    The characterization of cord blood hemoglobin at the molecular level is a daunting challenge because hemoglobin F (HbF) and hemoglobin A (HbA) coexist in neonatal blood. We developed and validated a method using electrospray time-of-flight mass spectrometry (ES-TOF-MS) that measures, in a single analysis, relative levels of glycated and acetylated hemoglobin and allows the calculation of relative proportions of HbA, HbF(0), and HbF(1) in cord blood. Specific sections of acquired spectra were deconvoluted using a maximum entropy-based approach to true mass scale spectra. Mass precisions were less than 3 ppm with similar accuracies. Intra-interday precisions for α- and γ-chain glycation levels were 2.10%/3.72% and 2.75%/6.79%, respectively. The linearity of the α-chain glycation response was excellent (r(2) = 0.9990). We performed sample analysis on 39 cord blood specimens and found that the glycated α- and γ-chain levels were 2.27 ± 0.21% and 2.38 ± 0.29%, respectively, while the acetylated (G)γ and (A)γ-chain levels were 8.48 ± 0.53% and 7.14 ± 0.74%, respectively. We observed three types of HbF distinguishable by the intensities of γ-chain variants. Two-thirds of cord blood specimens were classified as HbF(I) with an intensity ratio (G)γ/(A)γ of 1.90 ± 0.12. For HbF(II) type (10/39 neonates), the intensity ratio of (G)γ/(A)γ was 3.71 ± 0.28. For three neonates with HbF(III), no (A)γ-chain was detected.

  7. Markers infectious agent in the cord blood samples public register of donors

    Directory of Open Access Journals (Sweden)

    A. B. Smoljaninov

    2014-01-01

    Full Text Available Objective. To evaluate the distribution of markers of infectious agents in umbilical cord blood samples Pokrovskij public stem cell bank donor registry for five years (2009 – 2013.Materials and Methods. 3533 plasma samples were investigatedafter selection during cord blood processing procedure for allogeneic use in Pokrovskij stem cell bank. All plasma samples were investigated in accordance with the Order of the Ministry of Health № 325 – 2003 by enzymelinked immunoassay method. In addition, during the period from November 2011 to December 2013 1030 plasma samples of umbilical cord blood were examined for the presence of HCV RNA, the RNA of HIV and HBV DNA.Results. Markers of the agents above have not been found in the plasma of 481 samples (13.6%. During the described period, no significant change in the share of samples containing antibodies to cytomegalovirus and toxoplasmosis (cytomegalovirus – 1978 samples (56%, Toxoplasma gondii – 112 samples (3.2%, 825 samples (23.4% cytomegalovirus and Toxoplasma gondii simultaneously were registered. 137 samples (3.9% were subjected to utilization in connection with detection of antibodies to HbcorAg – 116 samples (3.3%, antibodies to HCV – five samples (0.14%, and antibodies to Treponema pallidum – 16 samples (0.45%.Conclusion. The introduction of an additional method of polymerase chain reaction for the detection of nucleic acids of hepatitis viruses B, C, human immunodeficiency virus, along with study of cord blood samples by enzyme-linked immunoassay improve the quality of the control of the transmission of blood-borne infections.

  8. Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat.

    Science.gov (United States)

    Mothe, A J; Tator, C H

    2005-01-01

    Ependymal cells of the adult mammalian spinal cord exhibit stem/progenitor cell properties following injury. In the present study, we utilized intraventricular injection of 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3,3',3'-tetramethylindocarbocyanine (DiI) to label the ependyma lining the central canal to allow tracking of the migration of endogenous ependymal cells and their progeny after spinal cord injury (SCI). We developed a minimal injury model that preserved the integrity of the central canal and did not interfere with ependymal cell labeling. Three days following SCI, there was an 8.6-fold increase in the proliferative labeling index of the ependymal cells at the level of the needle track based on bromodeoxyuridine labeling, compared with 1 day post-injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells were not detected in the ependyma or surrounding gray matter, indicating that ependymal cells do not undergo apoptosis in response to minimal injury. Nestin was rapidly induced in the ependyma by 1 day and expression peaked by 7 days post-injury. We quantitated the number and distance of ependymal cell migration following minimal injury. The number of ependymal cells migrating from the region of the central canal increased by 3 days following minimal injury and DiI-labeled glial fibrillary acidic protein expressing cells were detected 14 days post-SCI, most of which migrated within 70 microm of the region of the central canal. These results show that a minimal SCI adjacent to the ependyma is sufficient to induce an endogenous ependymal cell response where ependymal stem/progenitor cells proliferate and migrate from the region of the central canal, differentiating primarily into astrocytes.

  9. Expansion of CD34+ cells from human umbilical cord blood by FL and/or TPO gene transfected human marrow stromal cell lines

    Institute of Scientific and Technical Information of China (English)

    张毅; 唐佩弦; 金滢; 李秀森; 张双喜; 吴英; 毛宁

    2001-01-01

    To elucidate the effect of gene transfected marrow stromal cell on expansion of human cord blood CD34+ cells, a culture system was established in which FL and TPO genes were transfected into human stromal cell line HFCL. To establish gene transfected stromal cells co-culture system, cord blood CD34+ cells were purified by using a magnetic beads sorting system. The number of all cells and the number of CD34+ cells and CFC (CFU-GM and BFU-E) were counted in different culture systems. The results showed that in all 8 culture systems, SCF+IL-3+HFT manifested the most potent combination, with the number of total nucleated cells increasing by (893.3±52.1)-fold, total progenitor cells (CFC) by (74.5±5.2)-fold and CD34+ cells by 15.7-fold.Maximal expansions of CFC and CD34+ cells were observed at the end of the second week of culture. Within 14 days of culture, (78.1 ± 5.5)-fold and (57.0 ± 19.7)-fold increases in CFU-GM and BFU-E were obtained. Moreover, generation of LTC-IC from amplified CD34+ cells within 28 days was found only in two combinations, I.e. SCF+IL-3+FL+TPO and SCF+IL-3+HFT, and there was no significant difference between these two groups statistically. These results suggest that human umbilical cord blood CD34+ cells can be extensively expanded ex vivo by using gene transfected stromal cells along with cytokines.

  10. Efficient removal of platelets from peripheral blood progenitor cell products using a novel micro-chip based acoustophoretic platform.

    Directory of Open Access Journals (Sweden)

    Josefina Dykes

    Full Text Available BACKGROUND: Excessive collection of platelets is an unwanted side effect in current centrifugation-based peripheral blood progenitor cell (PBPC apheresis. We investigated a novel microchip-based acoustophoresis technique, utilizing ultrasonic standing wave forces for the removal of platelets from PBPC products. By applying an acoustic standing wave field onto a continuously flowing cell suspension in a micro channel, cells can be separated from the surrounding media depending on their physical properties. STUDY DESIGN AND METHODS: PBPC samples were obtained from patients (n = 15 and healthy donors (n = 6 and sorted on an acoustophoresis-chip. The acoustic force was set to separate leukocytes from platelets into a target fraction and a waste fraction, respectively. The PBPC samples, the target and the waste fractions were analysed for cell recovery, purity and functionality. RESULTS: The median separation efficiency of leukocytes to the target fraction was 98% whereas platelets were effectively depleted by 89%. PBPC samples and corresponding target fractions were similar in the percentage of CD34+ hematopoetic progenitor/stem cells as well as leukocyte/lymphocyte subset distributions. Median viability was 98%, 98% and 97% in the PBPC samples, the target and the waste fractions, respectively. Results from hematopoietic progenitor cell assays indicated a preserved colony-forming ability post-sorting. Evaluation of platelet activation by P-selectin (CD62P expression revealed a significant increase of CD62P+ platelets in the target (19% and waste fractions (20%, respectively, compared to the PBPC input samples (9%. However, activation was lower when compared to stored blood bank platelet concentrates (48%. CONCLUSION: Acoustophoresis can be utilized to efficiently deplete PBPC samples of platelets, whilst preserving the target stem/progenitor cell and leukocyte cell populations, cell viability and progenitor cell colony-forming ability

  11. Allergen specific responses in cord and adult blood are differentially modulated in the presence of endotoxins

    DEFF Research Database (Denmark)

    Eiwegger, T.; Mayer, E.; Pedersen, Susanne Brix;

    2008-01-01

    Background Endotoxins are common contaminants in allergen preparations and affect antigen-specific cellular responses. Distinct effects of endotoxin on cells in human umbilical cord and adult blood are poorly defined. Objectives To examine the effect of endotoxins in allergen preparations...... on cellular responses in human cord and peripheral blood (PB). Methods The endotoxin content in beta lactoglobulin (BLG), the peanut allergen Ara h 1 and the major birch pollen allergen Bet v 1 was assessed. Proliferation and cytokine response of mononuclear cells towards contaminated and lipopolysaccharide...... (LPS)-free allergens were evaluated at different time-points. Fractions of contaminated BLG were generated and assayed on their immuno-stimulatory capacity. The involvement of toll-like receptor (TLR) 2 and 4 was investigated by blocking antibodies and TLR-transfected human embryonic kidney cells...

  12. Correlations between stress hormone levels in umbilical cord blood and duration of delivery.

    Science.gov (United States)

    Sano, Yoko; Doi, Takayuki; Kikuchi, Suguru; Kawai, Kennta; Tanaka, Minoru

    2015-07-01

    Correlations between umbilical cord blood concentration of stress response hormone cortisol and prolactin, and delivery duration were examined. Thirty-three cases were selected in which both mothers and neonates were healthy, and the neonates were delivered at full term. The umbilical cord blood was collected at the time of delivery and concentrations of cortisol and prolactin were measured. The cortisol level was significantly higher after vacuum-assisted delivery than after spontaneous delivery (p=0.044). Significant positive correlations (p=0.0289) were observed between cortisol level and delivery duration. In particular, the duration of the second stage of delivery showed stronger positive correlation (p=0.0304) with the cortisol level. The prolactin level showed weak correlation with the duration of full delivery and the second stage of delivery. The findings suggest that foetuses may respond to stress by uterine contraction during delivery.

  13. Umbilical cord blood banking: from personal donation to international public registries to global bioeconomy

    Directory of Open Access Journals (Sweden)

    Petrini C

    2014-06-01

    Full Text Available Carlo Petrini Italian National Institute of Health, Rome, Italy Abstract: The procedures for collecting voluntarily and freely donated umbilical cord blood (UCB units and processing them for use in transplants are extremely costly, and the capital flows thus generated form part of an increasingly pervasive global bioeconomy. To place the issue in perspective, this article first examines the different types of UCB biobank, the organization of international registries of public UCB biobanks, the optimal size of national inventories, and the possibility of obtaining commercial products from donated units. The fees generally applied for the acquisition of UCB units for transplantation are then discussed, and some considerations are proposed regarding the social and ethical implications raised by the international network for the importation and exportation of UCB, with a particular emphasis on the globalized bioeconomy of UCB and its commerciality or lack thereof. Keywords: cord blood banking, economy, ethics, stem cells, transplantation

  14. Cellular and antibody response to respiratory syncytial (RS) virus in human colostrum, maternal blood, and cord blood.

    Science.gov (United States)

    Scott, R; Scott, M; Toms, G L

    1981-01-01

    Samples of colostrum, maternal blood, and cord blood from a group of 21 women were examined for the presence of cellular reactivity to respiratory syncytial (RS) virus using a transformation assay and for the level of specific IgA, and IgG, and IgM antibodies to RS virus by membrane immunofluorescence. Six of the 18 colostral cell cultures and six of the 16 maternal blood cultures gave a significant proliferative response to RS virus antigen, although a positive response in both local and systemic cell cultures was found in only one another. In addition, one of 18 samples of cord blood gave a proliferative response to RS virus antigen. Detectable titres of IgA antibodies to RS virus were found in 15 of the 20 samples of colostral whey and in 13 of the 17 samples of maternal plasma examined. RS virus-specific IgG antibodies were detected in 10 of 20 colostral whey samples and in all samples of maternal cord plasma. In this study, it was not possible to demonstrate a relationship between a positive proliferative response of colostral cell cultures to RS virus and the level of specific IgA and IgG antibodies in colostral whey. Similarly, the proliferative response of material blood cultures was unrelated to the titre of specific IgA or IgG antibodies in maternal plasma. The relevance of the local cellular proliferative response to RS virus in colostral cell cultures to the protection afforded by breast-feeding is discussed.

  15. Hemopoietic progenitor cell identification in fetal and adult blood Célula progenitora hamatopoética - identificação em sangue fetal e de adulto

    Directory of Open Access Journals (Sweden)

    Aixa Müller

    2008-06-01

    Full Text Available Hemopoietic progenitor cells give rise to all cellular elements of the blood and are of importance as a potential source of cells used for correction of various pathological conditions. The main objective of this study was to identify and quantitative hemopoietic progenitor cell in antenatal fetal blood, in cord blood at the time of delivery and in adult blood, using monoclonal antibodies to surface markers and flow cytometry. CD34+ cells, most of them probably representing progenitor cells, were detected in prenatal fetal blood as early as the 17th week of gestation. The proportion of these cells showed a tendency to decrease as the pregnancy progressed. Within the population of CD34+ cells, a relatively low proportion (less than 1% were negative for the surface marker CD33 or HLA-Dr, indicating a population of primitive stem cells, i.e., progenitor cells no committed to a specific lineage. On the contrary, another group coexpressed CD33 or HLA-Dr, being more mature progenitor cells already committed to differentiate along a specific lineage. The percentage of CD34+ obtained in blood of adult patients after mobilization with chemotherapeutic agents and growth factors showed an average value of 2.7± 3.1%. The percentage of CD34+ in the apheresis products of various patients varied from 0.58 to 1.48. In some cases the cells were reinfused in the patient with good results. Our findings are in agreement with previous studies suggesting that CD34+ stem cells is a heterogeneous population, with each subset having variable degree o commitment to differentiate toward a specific cell lineage.As células progenitoras hematopoéticas são as responsáveis pela produção de todos os elementos do sangue e são as potenciais fontes de células usadas para o tratamento de várias condições patológicas. O principal objetivo deste trabalho foi identificar e quantificar as células progenitoras hematopoiéticas no sangue fetal do período pré-natal, no

  16. Changes of Number and Function of Late Endothelial Progenitor Cells in Peripheral Blood of COPD Patients Combined with Pulmonary Hypertension.

    Science.gov (United States)

    Liu, Pei; Zhang, Hongmei; Liu, Jianxin; Sheng, Chunfeng; Zhang, Linlin; Zeng, Yanjun

    2016-06-01

    Objective The objective of this study was to investigate the changes of number and function of late endothelial progenitor cells (EPCs) in peripheral blood of chronic obstructive pulmonary disease (COPD) patients combined with pulmonary hypertension. Subjects and Methods The study enrolled 120 cases including 40 non-COPD and pulmonary arterial hypertension (PAH) patients (non-COPD group), 40 COPD non-PAH patients (COPD group), and 40 COPD patients combined with PAH (COPD + PAH group). Peripheral blood mononuclear cells were separated by density gradient centrifugation, cultured for 21 days, and then identified as late endothelial progenitor cells. The cell colonies were counted. MTT assay, modified Boyden chamber assay, and human fibronectin plates were used to measure the proliferation, migration, and adhesion functions of the late endothelial progenitor cells, respectively. Results Compared with non-COPD and COPD groups, the number of peripheral blood late EPCs in COPD + PAH group was significantly reduced, and the proliferation, adhesion, and migration capacities were significantly lowered; the differences were statistically significant (p number and function of late EPCs decreased with the increase of pulmonary artery pressure (p number of late EPCs in COPD patients combined with pulmonary hypertension was reduced, which implies the impaired cell functions. The changes of number and function were negatively correlated with the severity of pulmonary hypertension.

  17. Metabolic targets of endocrine disrupting chemicals assessed by cord blood transcriptome profiling

    DEFF Research Database (Denmark)

    Remy, Sylvie; Govarts, Eva; Wens, Britt

    2016-01-01

    Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic......’ pathways were significantly enriched in relation to p,p′-DDE. Transcriptional changes at birth suggest a role for specific metabolic targets as a link between prenatal EDC exposure and metabolic disorders later in life. © 2016 Elsevier Inc....

  18. The Blood-testis-barrier and Male Sexual Dysfunction Following Spinal Cord Injury

    Science.gov (United States)

    2013-10-01

    dependent male infertility is characterized by a significant reduction in numbers and quality of functional sperm. The mechanism(s) underlying this...during the terminal endstage procedures. Under my direction , Ryan has been responsible for performing all animal surgeries listed under the first...term effects on the blood-testis-barrier as a mechanism underlying male infertility following spinal cord injury. Goals/Milestones (Example) CY12/13

  19. [Cord blood procalcitonin in the assessment of early-onset neonatal sepsis].

    Science.gov (United States)

    Oria de Rueda Salguero, Olivia; Beceiro Mosquera, José; Barrionuevo González, Marta; Ripalda Crespo, María Jesús; Olivas López de Soria, Cristina

    2017-08-01

    Early diagnosis of early-onset neonatal sepsis (EONS) is essential to reduce morbidity and mortality. Procalcitonin (PCT) in cord blood could provide a diagnosis of infected patients from birth. To study the usefulness and safety of a procedure for the evaluation of newborns at risk of EONS, based on the determination of PCT in cord blood. Neonates with infectious risk factors, born in our hospital from October 2013 to January 2015 were included. They were processed according to an algorithm based on the values of cord blood procalcitonin (< 0.6ng/ml versus ≥0.6ng/ml). They were later classified as proved infection, probable, or no infection. Of the 2,519 infants born in the study period, 136 met inclusion criteria. None of 120 cases with PCT<0.6ng/ml in cord blood developed EONS (100% negative predictive value). On the other hand, of the 16 cases with PCT ≥0.6ng/ml, 10 were proven or probably infected (62.5% positive predictive value). The sensitivity of the PCT against infection was 100%, with a specificity of 95.2% (area under the receiver operator curve 0.969). The incidence of infection in the study group was 7.4%, and 26.1% in cases with maternal chorioamnionitis. 21 newborn (15.4%) received antibiotic therapy. The studied protocol has shown to be effective and safe to differentiate between patients with increased risk of developing an EONS, in those where the diagnostic and therapeutic approach was more interventionist, versus those with less likelihood of sepsis, who would benefit from a more conservative management. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Relationship between gestational age and endoglin levels in maternal and cord blood

    OpenAIRE

    Simmi Kharb; Tiwari, R; Nanda, S

    2016-01-01

    Background: Poor placentation at early gestational age is an important predisposing condition for the development of preeclampsia. The present study was designed to study the relationship of gestational age with endoglin levels in maternal and cord blood of normal and pre-eclamptic women. Methods: The present study was conducted in fifty pregnant women that were grouped as: group 1 (control, n=25) comprising of normotensive women immediately after delivery, group 2 (study group, n=25) comp...

  1. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

    Science.gov (United States)

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. Conclusion This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and

  2. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis.

    Science.gov (United States)

    Cizmeci, Mehmet Nevzat; Kara, Semra; Kanburoglu, Mehmet Kenan; Simavli, Serap; Duvan, Candan Iltemur; Tatli, Mustafa Mansur

    2014-03-01

    Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism's access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min-max: 118.1-8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    Science.gov (United States)

    Mithal, Leena B; Palac, Hannah L; Yogev, Ram; Ernst, Linda M; Mestan, Karen K

    2017-01-01

    Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  4. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia

    DEFF Research Database (Denmark)

    Ruggeri, A; Labopin, M; Sanz, G;

    2015-01-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared ...

  5. 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.

  6. 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...

  7. Cord blood collection and banking from a population with highly diverse geographic origins increase HLA diversity in the registry and do not lower the proportion of validated cord blood units: experience of the Marseille Cord Blood Bank.

    Science.gov (United States)

    Bordoni, C; Magalon, J; Gilbertas, C; Gamerre, M; Le Coz, P; Berthomieu, M; Chabannon, C; Di Cristofaro, J; Picard, C

    2015-04-01

    Several Cord Blood (CB) Bank studies suggested that ethnicity impaired CB unit (CBU) qualification. The Bone Marrow Donors Worldwide registries present an over-representation of unrelated donors (UD) from Northwestern European descent. This raises the question of equality of access to hematopoietic stem cells transplant, especially in the Mediterranean zone, which has taken in many waves of immigration. The aim of our study is to address whether, in the Marseille CB Bank, CBU qualification rate is impaired by geographic origin. The study compared biological characteristics of 106 CBU disqualified for total nucleated cell (TNC) count (dCBU) and 136 qualified CBU in relation to registry enrichment and haplotype origin. A high proportion (>80%) of both dCBU and CBU had at least one non-European haplotype and enrich CB and UD registries to a higher extent than those with two European haplotypes (PBank inventories and to improve the representation of minorities.

  8. Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation

    Directory of Open Access Journals (Sweden)

    Wang Feng-Chao

    2010-10-01

    Full Text Available Abstract Background Transplantation of oligodendrocyte precursor cells (OPCs is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. Results We transplanted green fluorescent protein (GFP expressed OPCs (GFP-OPCs into injured spinal cords of rats treated with or without CsA (10 mg/kg. Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI. Conclusions These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

  9. The relationship between perchlorate in drinking water and cord blood thyroid hormones: First experience from Iran

    Directory of Open Access Journals (Sweden)

    Ashraf Javidi

    2015-01-01

    Full Text Available Background: Considering the controversial information regarding the effects of perchlorate on thyroid function of high risk population as neonates, and given the high prevalence rate of thyroid disorders specially congenital hypothyroidism in our region, this study aims to investigate for the first time in Iran, the relationship between drinking groundwater perchlorate and cord blood thyroid hormones level in an industrial region. Methods: In this cross-sectional study, drinking groundwater perchlorate level of rural areas of Zarinshahr, Isfahan was measured. Simultaneously, cord blood level of thyroid hormones of neonates born in the studied region was measured. Thyroid function test of neonates in regions with low and high perchlorate level were compared. Results: In this study, 25 tap water samples were obtained for perchlorate measurement. Level of cord blood thyroid stimulating hormone (TSH, T4 and T3 of 25 neonates were measured. Mean (standard deviation of perchlorate, TSH, T4 and T3 was 3.59 (5.10 μg/l, 7.81 (4.14 mIU/m, 6.06 (0.85 mg/dl, and 63.46 (17.53 mg/dl, respectively. Mean levels of thyroid function tests were not different in low ( 0.05. Conclusions: Perchlorate did not appear to be related to thyroid function of neonates in the studied industrial region. It seems that iodine status of the regions, as well as other environmental contaminants and genetic background, could impact on its relation with thyroid function of neonates.

  10. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  11. Leukemia cell microvesicles promote survival in umbilical cord blood hematopoietic stem cells.

    Science.gov (United States)

    Razmkhah, Farnaz; Soleimani, Masoud; Mehrabani, Davood; Karimi, Mohammad Hossein; Kafi-Abad, Sedigheh Amini

    2015-01-01

    Microvesicles can transfer their contents, proteins and RNA, to target cells and thereby transform them. This may induce apoptosis or survival depending on cell origin and the target cell. In this study, we investigate the effect of leukemic cell microvesicles on umbilical cord blood hematopoietic stem cells to seek evidence of apoptosis or cell survival. Microvesicles were isolated from both healthy donor bone marrow samples and Jurkat cells by ultra-centrifugation and were added to hematopoietic stem cells sorted from umbilical cord blood samples by magnetic associated cell sorting (MACS) technique. After 7 days, cell count, cell viability, flow cytometry analysis for hematopoietic stem cell markers and qPCR for P53 gene expression were performed. The results showed higher cell number, higher cell viability rate and lower P53 gene expression in leukemia group in comparison with normal and control groups. Also, CD34 expression as the most important hematopoietic stem cell marker, did not change during the treatment and lineage differentiation was not observed. In conclusion, this study showed anti-apoptotic effect of leukemia cell derived microvesicles on umbilical cord blood hematopoietic stem cells.

  12. Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Aebi Christoph

    2011-05-01

    Full Text Available Abstract Background Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Methods Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30, chorioamnionitis (n = 33 and asphyxia (n = 25 were compared to a control group of preterm and term (n = 155 neonates. Results Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419. Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p Conclusions Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS.

  13. Organochlorine pesticide levels in umbilical cord blood of newborn in Veracruz, Mexico.

    Science.gov (United States)

    Herrero-Mercado, Margarita; Waliszewski, S M; Caba, M; Martínez-Valenzuela, C; Hernández-Chalate, F

    2010-10-01

    Organochlorine pesticides accumulate in lipid rich compartments of organisms. During pregnancy, the compounds pass through the placental barrier appear in cord blood. The aim of this study was to monitor the levels of organochlorine pesticides in 70 umbilical cord blood samples taken during deliveries in Veracruz in 2009. For organochlorine pesticides, only the presence β-HCH (4%, 3.9 μg/L median concentration on wet weight), pp'DDE (100%, 0.7 μg/L) and pp'DDT (4%, 1.4 μg/L) were detected. The total pool of samples divided according to sex of new born babies, showed no statistical differences among median concentrations. The number of deliveries considered as a determinant contamination factor affirmed there were no statistical differences among median concentrations; however pp'DDE levels increased from the one to two childbirth groups. Age of pregnant women as a discriminate factor manifests in a significant increase in contamination levels among first, second and third tertile. In general, umbilical cord blood samples in Veracruz contained organochlorine pesticides, especially pp'DDE, confirming the presence of these compounds in the environment and their transfer from the mother to the developing fetus.

  14. Cocultivation of umbilical cord blood CD34+ cells with retro-transduced hMSCs leads to effective amplification of long-term culture-initiating cells

    Institute of Scientific and Technical Information of China (English)

    Chun-Gang Xie; Jin-Fu Wang; Ying Xiang; Li-Yan Qiu; Bing-Bing Jia; Li-Juan Wang; Guo-Zhong Wang; Guo-Ping Huang

    2006-01-01

    AIM: To establish a novel coculture system for ex vivo expansion of umbilical cord blood(UCB) hematopoietic progenitors using thrombopoietin (TPO)/Flt-3 ligand(FL)-transduced human marrow-derived mesenchymal stem cells (tfhMSCs) as feeder.METHODS: UCB CD34+ cells were isolated and cultured using four culture systems in serum-containing or serumfree medium. Suitable aliquots of cultured cells were used to monitor cell production, clonogenic activity,and long-term culture-initiating culture (LTC-IC) output.Finally, the severe-combined immunodeficient (SCID)mouse-repopulating cell (SRC) assay was performed to confirm ability of the cultured cells to reconstitute longterm hematopoiesis.RESULTS: There were no significant differences in the number of total nucleated cells among different culture systems in serum-containing medium during 21-d culture. However, on d 14, the outputs of CD34+ cells,CFU-C and CFU-GEMM in tfhMSCs coculture system were significantly enhanced. LTC-IC assay demonstrated that the tfhMSCs coculture system had the most powerful activity. The severe-combined immunodeficient (SCID)mouse repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. Furthermore, PCR analysis demonstrated the presence of human hematopoietic cells in the bone marrow and peripheral blood cells of NOD/SCID mice.CONCLUSION: The TPO/FL-transduced hMSCs, in combination with additive cytokines, can effectively expand hematopoietic progenitors from UCB in vitro and the tfhMSCs coculture system may be a suitable system for ex vivo manipulation of primitive progenitor cells under contact culture conditions.

  15. Cord blood IgE. II. Prediction of atopic disease. A follow-up at the age of 18 months

    DEFF Research Database (Denmark)

    Hansen, L G; Høst, A; Halken, S;

    1992-01-01

    size with cord blood IgE less than 0.5 kU/l. A total of 762 infants were clinically evaluated at 18 months of age. A diagnosis of definite atopy, probable atopy or no atopy, including both IgE and non-IgE mediated disease was established. Applying different cord blood IgE cut-off values (0.3, 0.5, 0...

  16. Delayed umbilical cord clamping at birth has effects on arterial and venous blood gases and lactate concentrations.

    Science.gov (United States)

    Wiberg, N; Källén, K; Olofsson, P

    2008-05-01

    To estimate the influence of delayed umbilical cord clamping at birth on arterial and venous umbilical cord blood gases, bicarbonate (HCO3-), base excess (BE) and lactate in vigorous newborns. University hospital. Prospective observational. Vaginally delivered term newborns. Umbilical cord arterial and venous blood was sampled repeatedly every 45 seconds (T(0)= time zero; T(45)= 45 seconds, T(90)= 90 seconds) until the cord pulsations spontaneously ceased in 66 vigorous singletons with cephalic vaginal delivery at 36-42 weeks. Longitudinal comparisons were performed with the Wilcoxon signed-ranks matched pairs test. Mixed effect models were used to describe the shape of the regression curves. Longitudinal changes of umbilical cord blood gases and lactate. In arterial cord blood, there were significant decreases of pH (7.24-7.21), HCO3- (18.9-18.1 mmol/l) and BE (-4.85 to -6.14 mmol/l), and significant increases of PaCO(2) (7.64-8.07 kPa), PO(2) (2.30-2.74 kPa) and lactate (5.3-5.9 mmol/l) from T(0) to T(90), with the most pronounced changes at T(0)-T(45). Similar changes occurred in venous blood pH (7.32-7.31), HCO3- (19.54-19.33 mmol/l), BE (-4.93 to -5.19 mmol/l), PaCO(2) (5.69-5.81 kPa) and lactate (5.0-5.3 mmol/l), although the changes were smaller and most pronounced at T(45)-T(90). No significant changes were observed in venous PO(2). Persistent cord pulsations and delayed cord clamping at birth result in significantly different measured values of cord blood acid-base parameters.

  17. The regulation of method of tonifying Qi and activating blood circulation in the related gene expressions after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Xiao Fan; Li Zhang

    2016-01-01

    Spinal cord injury is a disease of high incidence and low cure rate without any ideal treatment. Among the complex pathological reactions, the post-injury abnormal expressions of many genes may be an important one. Method of tonifying Qi and activating blood circulation, which is one of the most important treatments of spinal cord injury in Traditional Chinese Medicine and has been used extensively in clinic, is proved to be effective in the treatment of spinal cord injury. Recently, many scholars have carried out a lot of studies in this filed and acquired notable achievements. The essay concludes mechanisms of the regulation of method of tonifying Qi and activating blood circulation in the related gene expressions after spinal cord injury to provide new thoughts and new methods for the treatment and study of spinal cord injury.

  18. The Contact Activation System (CAS) in cord blood: Measurement of CAS components and comparison with mother's blood. A pilot study.

    Science.gov (United States)

    Uszyński, Mieczysław; Kuczyński, Jarosław; Żekanowska, Ewa; Uszyński, Waldemar

    2015-11-01

    Classical reference data concerning the coagulation system and fibrinolysis in fetuses and newborns date back to the 1990 s. Since that time a number of methodological or other improvements have been implemented, which may cast some doubt on timeliness of the data. The study objective was to measure the levels of Contact Activation System (CAS) components by antigen, i.e. factors XII and XI (FXII, FXI), prekallikrein (PK) and high molecular weight kininogen (HMWK) in cord blood and maternal blood. The study group consisted of 35 healthy parturient women with an uneventful pregnancy and birth. The samples of cord blood and maternal blood were obtained immediately after delivery, before clumping the umbilical cord. The CAS components were measured by immunoenzymatic method (ELISA). The median concentrations of CAS components in cord blood plasma and mother's plasma were as follow: FXII: 1.02 (0.60- 2.58) ng/mg protein vs. 0.94 (0.66-1.86) ng/mg protein (p>0.05); FXI: 2.71(0.03-8.0) ng/mg protein vs. 0.92 (0.03-10.44) ng/mg protein (p>0.05); PK: 168.78 (104.28-261.16) pg/mg protein vs. 113.44 (79.94-146.70) pg/mg protein (p>0.05); HMWK: 2169.45 (1530.64- 2539.83) ng/mg protein vs. 2857.96 (2541.52-3161.04) ng/mg protein (pblood of full-term and healthy fetuses were similar to those observed in mother's blood immediately after delivery. Only high molecular weight kininogen was found to be lower (accounting for 84% of the values noted in mothers). 2. Based on our measurements, we claim that the cited reference data concerning the contact factors in full-term and healthy newborns are underestimated; hence, new reference values need to be determined for each antigen and activity contact factor level. Copyright © 2015. Published by Elsevier Ltd.

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

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    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.

  20. 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.

  1. Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury.

    Science.gov (United States)

    Lee, Jee Y; Choi, Hae Y; Yune, Tae Y

    2016-10-01

    Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI.

  2. Effects of L-lysine monohydrochloride on insulin and blood glucose levels in spinal cord injured rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tian-ling; ZHAO Yu-wu; LIU Xue-yuan; DING Su-ju

    2010-01-01

    Background Hyperglycemia in brain and spinal cord could aggravate neurologic impairment. Recent studies showed that L-lysine monohydrochlonde (LMH) could increase the insulin secretion and regulate the blood glucose level. The aim of the present study was to investigate the effects of LMH on pancreatic islet B cells, the levels of endogenous insulin and blood glucose in spinal cord injured rats.Methods Forty male Wistar rats were divided into four groups, namely, normal control group, model group, high-dose LMH group (621.5 mg/kg equal to LMH 1/8 LD50), and low-dose LMH group (310.8 mg/kg equal to LMH 1/16 LD50). The model of spinal cord injured rat was established by hemi-transection at the lower right thoracic spinal cord. LMH was administered via intraperitoneal injection once spinal cord injury was produced in rats. All rats were sacrificed 48 hours after spinal cord injured. The effects of LMH on pancreatic islet B cells, the content of endogenous insulin, end the level of blood glucose were observed with immunohistochemical method, radioimmunoassay method, end biochemical analyzer, respectively. Results The insulin immunohistochemical intensities of islet B cells were significantly weaker in model group then those in normal control group (P 0.05). Conclusion LMH, but dose-dependent, might participate in the regulation of pancreatic islet B cells, and then reduce the blood glucose levels in the spinal cord injured rats.

  3. Contradictions of value: between use and exchange in cord blood bioeconomy.

    Science.gov (United States)

    Brown, Nik

    2013-01-01

    Umbilical cord blood (CB) has become established as an increasingly viable clinical alternative to bone marrow in the treatment of leukaemia leading to the construction of a global network of CB banks promoted through a moral ethos of gift. Additionally, some banks offer the opportunity to retain stem cells privately. CB is discursively presented as clinical 'waste', a 'by-product' of birthing. In this way CB units are made available to a global exchange-based bioeconomy. Crucially, CB collection has developed in parallel with several necessary obstetric practices, especially the immediate clamping of the cord following delivery, essential to high volume collection. However, this article strongly suggests the promotional basis of CB banking (such as by gift, waste or donation) is in tension with the growing preference of new parents to delay cord clamping. Based on focus groups with expectant parents, the promotion of CB banking can in fact be seen to feed into critical reflection on the value of CB for newborn infants, potentially reinvigorating a tradition of delayed umbilical cord clamping. Theoretically, these contradictory systems of valuing are conceptualised through recent literature on bioeconomy and Marx's writings on the contrasting tensions between use and exchange value. © 2012 The Author. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  4. Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood.

    Science.gov (United States)

    Rosa, Maria José; Just, Allan C; Guerra, Marco Sánchez; Kloog, Itai; Hsu, Hsiao-Hsien Leon; Brennan, Kasey J; García, Adriana Mercado; Coull, Brent; Wright, Rosalind J; Téllez Rojo, Martha María; Baccarelli, Andrea A; Wright, Robert O

    2017-01-01

    Changes in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ≤2.5μm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5 exposure using mtDNA content measured in cord blood. Women affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study. Mothers with cord blood collected at delivery and complete covariate data were included (n=456). Mothers' prenatal daily exposure to PM2.5 was estimated using a satellite-based spatio-temporally resolved prediction model and place of residence during pregnancy. DNA was extracted from umbilical cord leukocytes. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA content. A distributive lag regression model (DLM) incorporating weekly averages of daily PM2.5 predictions was constructed to plot the association between exposure and OS over the length of pregnancy. In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, birth year, maternal education, and assay batch, we found significant associations between higher PM2.5 exposure during late pregnancy (35-40weeks) and lower mtDNA content in cord blood. Increased PM2.5 during a specific prenatal window in the third trimester was associated with decreased mtDNA content suggesting heightened sensitivity to PM-induced OS during this life stage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication

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    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

  6. Umbilical cord blood testosterone and childhood internalizing and externalizing behavior: a prospective study.

    Directory of Open Access Journals (Sweden)

    Monique Robinson

    Full Text Available Antenatal testosterone exposure influences fetal neurodevelopment and gender-role behavior in postnatal life and may contribute to differences in developmental psychopathology during childhood. We prospectively measured the associations between umbilical cord blood testosterone levels at birth and childhood behavioral development in both males and females from a large population based sample. The study comprised 430 females and 429 males from the Western Australian Pregnancy Cohort (Raine Study where umbilical cord blood had been collected. Total testosterone concentrations were determined by mass spectrometry and bioavailable testosterone (BioT levels were calculated. At two, five, eight and ten years of age, the participants completed the Child Behavior Checklist (CBCL. Linear regression models were used to analyse the relationship between BioT concentrations (in quartiles and CBCL scores (total, internalizing, externalizing and selected syndrome. Boys had higher mean CBCL T-scores than girls across all ages of follow-up. There was no significant relationship between cord blood BioT quartiles and CBCL total, internalizing and externalizing T-scores at age two or five to ten combined. In the syndrome score analyses, higher BioT quartiles were associated with significantly lower scores for attention problems for boys at age five, eight and ten, and greater withdrawal symptoms in pre-school girls (age five. We did not identify a consistent relationship between antenatal testosterone exposure and total, internalizing or externalizing behavioral difficulties in childhood. Higher umbilical cord BioT levels were associated with lower scores for attention problems in boys up to 10 years and more withdrawn behavior in 5-year-old girls; however, these findings were not consistent across ages and require further investigation in a larger sample.

  7. Thyroid stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers' diseases

    Directory of Open Access Journals (Sweden)

    Laura Sterian Ward

    2000-09-01

    Full Text Available CONTEXT: Screening programs not only offer the opportunity to trace and treat almost all cases of congenital hypothyroidism but also mean large savings to the health system. However, carefully planned strategies are necessary to extend their benefits and reduce costs. OBJECTIVE: To determine the possible influence of maternal diseases that affect maternal-fetal placenta dynamics on primary thyroid stimulating hormone (TSH screening for congenital hypothyroidism. DESIGN: Prospective non-randomized clinical trial with at least 3 months of follow-up. SETTING: A public university referral center [CAISM/Hospital das Clínicas, Faculty of Medicine, University of Campinas, Campinas, SP]. PARTICIPANTS: 415 neonates divided into 5 groups: eighty-three infants born from cardiac mothers; 98 from mothers that had toxemia; 54 of the mothers had diabetes mellitus; 40 were HIV positive and 140 had no diseases. INTERVENTION: All newborns had cord blood samples collected on filter paper at birth. MAIN MEASUREMENTS: TSH was measured from dried blood spots using a homemade immunofluorescence assay (sensitivity in dried blood spots = 0.1 mU/L. RESULTS: There was no significant difference in the mean TSH levels among the 5 groups. Moreover, TSH levels were around 5 mU/L in 48% of the newborns, indicating that our region is severely deficient in iodine. CONCLUSIONS: Our results indicate that primary TSH screening programs using cord blood are not affected by maternal diseases. We suggest that, besides its technical advantages over heel punctures with T4 primary approaches, neonatal screening using primary cord blood TSH may also be used as a monitoring tool for evaluation and control of iodine deficiency disorders (IDD.

  8. Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification.

    Science.gov (United States)

    Gandillet, Arnaud; Serrano, Alicia G; Pearson, Stella; Lie-A-Ling, Michael; Lacaud, Georges; Kouskoff, Valerie

    2009-11-26

    The molecular mechanisms that regulate the balance between proliferation and differentiation of precursors at the onset of hematopoiesis specification are poorly understood. By using a global gene expression profiling approach during the course of embryonic stem cell differentiation, we identified Sox7 as a potential candidate gene involved in the regulation of blood lineage formation from the mesoderm germ layer. In the present study, we show that Sox7 is transiently expressed in mesodermal precursors as they undergo specification to the hematopoietic program. Sox7 knockdown in vitro significantly decreases the formation of both primitive erythroid and definitive hematopoietic progenitors as well as endothelial progenitors. In contrast, Sox7-sustained expression in the earliest committed hematopoietic precursors promotes the maintenance of their multipotent and self-renewing status. Removal of this differentiation block driven by Sox7-enforced expression leads to the efficient differentiation of hematopoietic progenitors to all erythroid and myeloid lineages. This study identifies Sox7 as a novel and important player in the molecular regulation of the first committed blood precursors. Furthermore, our data demonstrate that the mere sustained expression of Sox7 is sufficient to completely alter the balance between proliferation and differentiation at the onset of hematopoiesis.

  9. Distribution and Predictors of Pesticides in the Umbilical Cord Blood of Chinese Newborns.

    Science.gov (United States)

    Silver, Monica K; Shao, Jie; Chen, Minjian; Xia, Yankai; Lozoff, Betsy; Meeker, John D

    2015-12-30

    Rates of pesticide use in Chinese agriculture are five times greater than the global average, leading to high exposure via the diet. Many are neurotoxic, making prenatal pesticide exposure a concern. Previous studies of prenatal exposure in China focused almost entirely on organochlorines. Here the study goals were to characterize the exposure of Chinese newborns to all classes of pesticides and identify predictors of those exposures. Eighty-four pesticides and 12 metabolites were measured in the umbilical cord plasma of 336 infants. Composite variables were created for totals detected overall and by class. Individual pesticides were analyzed as dichotomous or continuous, based on detection rates. Relationships between demographic characteristics and pesticides were evaluated using generalized linear regression. Seventy-five pesticides were detected. The mean number of detects per sample was 15.3. Increased pesticide detects were found in the cord blood of infants born in the summer (β = 2.2, p = 0.01), particularly in July (β = 4.0, p = 0.03). Similar trends were observed for individual insecticide classes. Thus, a summer birth was the strongest predictor of pesticide evidence in cord blood. Associations were more striking for overall pesticide exposure than for individual pesticides, highlighting the importance of considering exposure to mixtures of pesticides, rather than individual agents or classes.

  10. Blood supply to the thoracolumbar spinal cord in the laboratory mouse using corrosion and dissection techniques.

    Science.gov (United States)

    Flesarova, Slavka; Mazensky, David; Teleky, Jana; Almasiova, Viera; Holovska, Katarina; Supuka, Peter

    2016-01-01

    Mice are used frequently as experimental models in the study of ischemic spinal cord injury. The aim of the present study was to describe the arterial blood supply to the thoracolumbar spinal cord in the mouse. The study was carried out on 20 adult mice using the corrosion and dissection technique. Dorsal intercostal arteries were found as branches of the thoracic aorta: as 7 pairs in 80% of cases, as 8 pairs in 15% of cases and as 9 pairs in 5% of cases. The paired lumbar arteries arising from the abdominal aorta were present as 5 pairs in all cases. Along the entire thoracic and lumbar spinal regions, we observed left-sided branches entering the ventral spinal artery in 64.2% and right-sided branches in 35.8% of cases. Along the entire thoracic and lumbar spinal regions, the branches entering the dorsal spinal arteries were left-sided in 60.8% of cases and right-sided in 39.2% of cases. We found some variations in the site of origin of the artery of Adamkiewicz and in the number of dorsal spinal arteries. Documenting the anatomical variations in spinal cord blood supply in the laboratory mouse will aid the planning of future experimental studies and in determining the clinical relevance of such studies.

  11. Distribution and Predictors of Pesticides in the Umbilical Cord Blood of Chinese Newborns

    Directory of Open Access Journals (Sweden)

    Monica K. Silver

    2015-12-01

    Full Text Available Rates of pesticide use in Chinese agriculture are five times greater than the global average, leading to high exposure via the diet. Many are neurotoxic, making prenatal pesticide exposure a concern. Previous studies of prenatal exposure in China focused almost entirely on organochlorines. Here the study goals were to characterize the exposure of Chinese newborns to all classes of pesticides and identify predictors of those exposures. Eighty-four pesticides and 12 metabolites were measured in the umbilical cord plasma of 336 infants. Composite variables were created for totals detected overall and by class. Individual pesticides were analyzed as dichotomous or continuous, based on detection rates. Relationships between demographic characteristics and pesticides were evaluated using generalized linear regression. Seventy-five pesticides were detected. The mean number of detects per sample was 15.3. Increased pesticide detects were found in the cord blood of infants born in the summer (β = 2.2, p = 0.01, particularly in July (β = 4.0, p = 0.03. Similar trends were observed for individual insecticide classes. Thus, a summer birth was the strongest predictor of pesticide evidence in cord blood. Associations were more striking for overall pesticide exposure than for individual pesticides, highlighting the importance of considering exposure to mixtures of pesticides, rather than individual agents or classes.

  12. Lactate study using umbilical cord blood: agreement between Lactate Pro hand-held devices with blood gas analyser and evaluation of lactate stability over time.

    Science.gov (United States)

    Su, Tina Y; Reece, Mifanwy; Chua, Seng C

    2013-08-01

    Lactate measurements have become increasingly preferred over pH analysis in the evaluation of fetal acidaemia in labour. In a busy labour ward, often the umbilical cord may be sampled late and as a result yield unreliable lactate values. To investigate the agreement of hand-held device Lactate Pro with a reference method blood gas analyser and evaluate the stability of umbilical cord lactate values over time. Prospective study carried out at elective caesarean section. Sixteen umbilical cords were double clamped immediately after delivery with paired arterial and venous blood samples collected by an independent researcher, at varying time intervals, and processed by two Lactate Pro devices and a reference method blood gas analyser. A significant difference of -0.41 to 0.10 mmol/L was found when different groups of Lactate Pro devices were compared with blood gas analyser at lactate values up to 5.70 mmol/L, with average lactate value of 2.45 mmol/L. Over time, there is progressive rise in lactate samples obtained from the umbilical cord. Lactate Pro devices have a significant difference, but when used in clinical practice on cord blood after delivery, this is unlikely to be meaningful. In intrapartum fetal surveillance, a systematic overestimation might lead to unnecessary intervention. It is possible to retrospectively predict the likely level of lactate at birth in delayed cord samples. © 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  13. Evaluation of Malondialdehyde, Superoxide Dismutase and Catalase Activity in Fetal Cord Blood of Depressed Mothers

    Science.gov (United States)

    Camkurt, Mehmet Akif; Fındıklı, Ebru; Bakacak, Murat; Tolun, Fatma İnanç; Karaaslan, Mehmet Fatih

    2017-01-01

    Objective The umbilical cord consists of two arteries and one vein and it functions in the transport between the maternal and fetal circulation. Biochemical analysis of fetal cord blood (FCB) during delivery could be beneficial in terms of understanding the fetal environment. In this study, we aimed to investigate oxidative parameters like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in FCB during delivery. Methods We collected FCB samples during caesarean section. Our study included 33 depressed mothers and 37 healthy controls. We investigated MDA, SOD, and CAT levels in FCB samples. Results We found no significant difference between groups in terms of MDA (p=0.625), SOD (p=0.940), and CAT (p=0.413) levels. Conclusion Our study reveals probable protective effects of the placenta from oxidative stress. Future studies should include larger samples. PMID:28138108

  14. Cord Blood Banking in the Arab World: Current Status and Future Developments.

    Science.gov (United States)

    Matsumoto, Monica M; Dajani, Rana; Matthews, Kirstin R W

    2015-07-01

    Umbilical cord blood transplants are now used to treat numerous types of immune- and blood-related disorders and genetic diseases. Cord blood (CB) banks play an important role in these transplants by processing and storing CB units. In addition to their therapeutic potential, these banks raise ethical and regulatory questions, especially in emerging markets in the Arab world. In this article, the authors review CB banking in five countries in the region, Jordan, Saudi Arabia, Egypt, Qatar, and the United Arab Emirates, selected for their different CB banking policies and initiatives. In assessing these case studies, the authors present regional trends and issues, including religious perspectives, policies, and demographic risk factors. This research suggests strong incentives for increasing the number of CB units that are collected from and available to Arab populations. In addition, the deficit in knowledge concerning public opinion and awareness in the region should be addressed to ensure educated decision-making. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Cord blood hematopoietic cells from preterm infants display altered DNA methylation patterns.

    Science.gov (United States)

    de Goede, Olivia M; Lavoie, Pascal M; Robinson, Wendy P

    2017-01-01

    Premature infants are highly vulnerable to infection. This is partly attributable to the preterm immune system, which differs from that of the term neonate in cell composition and function. Multiple studies have found differential DNA methylation (DNAm) between preterm and term infants' cord blood; however, interpretation of these studies is limited by the confounding factor of blood cell composition. This study evaluates the epigenetic impact of preterm birth in isolated hematopoietic cell populations, reducing the concern of cell composition differences. Genome-wide DNAm was measured using the Illumina 450K array in T cells, monocytes, granulocytes, and nucleated red blood cells (nRBCs) isolated from cord blood of 5 term and 5 preterm ( 0.10) discovered between preterm and term infants compared to the preterm counterparts. Consistent shifts in DNAm between preterm and term cells were observed at 25 CpG sites, with many of these sites located in genes involved in growth and proliferation, hematopoietic lineage commitment, and the cytoskeleton. DNAm in preterm and term hematopoietic cells conformed to previously identified DNAm signatures of fetal liver and bone marrow, respectively. This study presents the first genome-wide mapping of epigenetic differences in hematopoietic cells across the late gestational period. DNAm differences in hematopoietic cells between term and preterm birth and DNAm could not be evaluated. These findings highlight gene regulatory mechanisms at both cell-specific and systemic levels that may be involved in fetal immune system maturation.

  16. 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.

  17. Evaluation of cefotaxime and desacetylcefotaxime concentrations in cord blood after intrapartum prophylaxis with cefotaxime.

    Science.gov (United States)

    Lepercq, Jacques; Treluyer, Jean Marc; Auger, Christelle; Raymond, Josette; Rey, Elisabeth; Schmitz, Thomas; Jullien, Vincent

    2009-06-01

    Preterm premature rupture of the membranes is associated with a high risk of neonatal sepsis. An increase in the incidence of early-onset neonatal sepsis due to ampicillin-resistant Escherichia coli in premature infants has been observed in the past few years. Intrapartum prophylaxis with ampicillin has proven to be efficient for the prevention of early neonatal sepsis due to group B streptococci. To date, there is no strategy for the prevention of early neonatal sepsis due to ampicillin-resistant E. coli. Our aim was to investigate whether a standardized dosage regimen of intrapartum cefotaxime could provide concentrations in the cord blood greater than the cefotaxime MIC(90) for E. coli. Seven pregnant women hospitalized with preterm premature rupture of the membranes and colonized with ampicillin-resistant isolates of the family Enterobacteriaceae were included. Cefotaxime was given intravenously during delivery, as follows: 2 g at the onset of labor and then 1 g every 4 h until delivery. Blood specimens were collected from the mother 30 min after the first injection and just before the second injection, and at birth, blood specimens were simultaneously collected from the mother and the umbilical cord. The concentrations of cefotaxime in the cord blood ranged from 0.5 to 8.5 mg/liter. The MIC(90) of cefotaxime for E. coli strains (0.125 mg/liter) was achieved in all cases. This preliminary study supports the use of cefotaxime for intrapartum prophylaxis in women colonized with ampicillin-resistant isolates of Enterobacteriaceae. The effectiveness of this regimen for the prevention of neonatal sepsis needs to be evaluated with a larger population.

  18. Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort.

    Science.gov (United States)

    Gossai, Anala; Lesseur, Corina; Farzan, Shohreh; Marsit, Carmen; Karagas, Margaret R; Gilbert-Diamond, Diane

    2015-01-01

    Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs+MMA+DMA) was associated with a 10.3% (95% CI: 0.8-20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: -1.0-18.6%) and 10.3% (95% CI: 1.2-20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: -3.4-17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth.

  19. The effect of time, temperature and storage device on umbilical cord blood gas and lactate measurement: a randomized controlled trial.

    Science.gov (United States)

    White, Christopher R H; Mok, Tabitha; Doherty, Dorota A; Henderson, Jennifer J; Newnham, John P; Pennell, Craig E

    2012-06-01

    Umbilical cord blood gas analysis has a significant and growing role in early neonatal assessment. Factors often delay analysis of cord blood allowing values to change. Consequently, this study evaluates the impact of time, temperature and method of storage on umbilical blood gas and lactate analyses. Umbilical cord segments from 80 singleton deliveries were randomized to: cords at room temperature (CR), cords stored on ice (CI), syringes at room temperature (SR) or syringes stored on ice (SI). Analysis occurred every 15 minutes for one-hour. Mixed model analysis of variance allowing for repeated measures was utilized. Cord arterial pH deteriorated in CR, CI, and SI within 15 minutes (p ≤ 0.001), with SR stable until 60 minutes (p = 0.002). Arterial pCO(2) remained stable in SR and CI, increased in SI (p = 0.002; 45 minutes) and decreased in CR (p blood gas values change rapidly after delivery. Smallest changes were seen in SR group. Data suggest that analyses should be conducted as soon as possible after delivery.

  20. Transplante de medula óssea e transplante de sangue de cordão umbilical em pediatria Bone marrow transplantation and cord blood transplantation in children

    Directory of Open Access Journals (Sweden)

    Cláudio Galvão de Castro Jr

    2001-10-01

    Full Text Available OBJETIVO: descrever as indicações, tipos, principais etapas e complicações do transplante de medula óssea, na forma de uma revisão, com a finalidade de facilitar a compreensão do processo pelo pediatra. FONTES DE DADOS: revisão bibliográfica sobre o tema, utilizando-se como base de dados o Medline. SÍNTESE DOS DADOS: são abordados os tipos de transplante de medula óssea autogênico, singênico e alogênico com suas indicações clínicas, os procedimentos de seleção de doadores, de coleta e infusão das células que irão reconstituir os sistemas hematopoético e imunológico. Expõem-se as alternativas para condicionamento pré-transplante e as novas fontes de células, como o sangue de cordão umbilical, descrevendo-se os resultados e as principais complicações relacionadas ao procedimento, tais como infecções oportunistas, doença enxerto contra hospedeiro, complicações hepáticas, gastrintestinais, gênito-urinárias e cárdio-respiratórias. Aborda-se o risco de complicações tardias e seu impacto na qualidade de vida pós-transplante. CONCLUSÕES: o transplante de medula óssea não proporciona a todos os pacientes uma sobrevida absolutamente normal, mas é um progresso considerável no tratamento das doenças que há pouco tempo não apresentavam alternativas terapêuticas satisfatórias. Conhecendo as diversas etapas do procedimento e sua morbidade, o pediatra pode representar uma fonte de informações aos pacientes com indicação de transplante de medula óssea e seus familiares.OBJECTIVE: to review the indications, main steps and complications of bone marrow transplantation in children. SOURCES: medline-based literature review. SUMMARY OF THE FINDINGS: we comment about the indications of autologous, allogeneic and syngeneic bone marrow transplantation, donor selections, harvest and infusion of the hematopoietic progenitor cells that will reconstitute the hematopoietic and immune systems. We describe the different

  1. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA.

    Directory of Open Access Journals (Sweden)

    J Richard Pilsner

    Full Text Available BACKGROUND: An emerging body of evidence indicates that early-life arsenic (As exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. OBJECTIVE: The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. DESIGN: Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs, maternal blood As (mbAs and cord blood As (cbAs. Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. RESULTS: In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1 and Q2 vs. Q4; p = 0.06 and 0.04, respectively. Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58 but negative among female newborns (N = 43; tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively and for the association between maternal uAs and LINE-1 (p = 0.07. Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05. CONCLUSIONS: These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm

  2. Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous transplantation.

    Science.gov (United States)

    Linker, Charles; Anderlini, Paolo; Herzig, Roger; Christiansen, Neal; Somlo, George; Bensinger, William; Fay, Joseph; Lynch, Joseph P; Goodnough, Lawrence T; Ashby, Mark; Benyunes, Mark C; Jones, Dennie V; Yang, Timothy A; Miller, Langdon L; Weaver, Charles

    2003-06-01

    This study assessed the ability of various schedules of recombinant human thrombopoietin (rhTPO) to enhance mobilization of peripheral blood progenitor cells (PBPCs) in 134 patients with cancer undergoing high-dose chemotherapy and autologous PBPC transplantation. Patients received the study drug on days 1, 3, and 5 before initiation of granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/day on day 5 and pheresis starting on day 9. Randomly assigned treatments on days 1, 3, and 5 were: group 1 (n=27) placebo, placebo, rhTPO 1.5 microg/kg; group 2 (n=27) rhTPO 1.5 microg/kg, placebo, placebo; groups 3 (n=28) and 4 (n=22) rhTPO 0.5 microg/kg on all 3 treatment days; and group 5 (n=30) placebo on all 3 treatment days. After high-dose chemotherapy and PBPC transplantation, groups 1 through 4 received rhTPO 1.5 microg/kg days 0, +2, +4, and +6 with either G-CSF 5 microg/kg/day (groups 1-3) or granulocyte-macrophage colony-stimulating factor 250 microg/m(2)/day (group 4). Group 5 received placebo plus G-CSF 5 microg/kg/day. The addition of rhTPO to G-CSF increased median CD34+ cell yield/pheresis in cohorts in which rhTPO was started before day 5, with higher yields in groups 2 (2.67 x 10(6)/kg) and groups 3 and 4 (3.10 x 10(6)/kg) than in group 1 (1.86 x 10(6)/kg) or group 5 (1.65 x 10(6)/kg) (P=.006 across groups). Comparing rhTPO to placebo, higher percentages of patients achieved the minimum yield of CD34+ > or =2 x 10(6)/kg (92% v 75%; P=.050) as well as the target yield of CD34+ > or =5 x 10(6)/kg (73% v 46%; P= .041). rhTPO-treated patients required fewer phereses to achieve minimum (P= .011) and target (P= .015) CD34+ cell values. rhTPO given after transplantation did not speed platelet recovery. No neutralizing antibodies were observed. We conclude that rhTPO can safely enhance mobilization of PBPC, reduce the number of leukapheresis, and allow more patients to meet minimal cell yield requirements to receive high-dose chemotherapy with PBPC

  3. Successful second transplantation from haploidentical donor for graft failure following unrelated cord blood cell transplantation or mismatched related transplantation: 2cases report

    Institute of Scientific and Technical Information of China (English)

    XU Lan-ping; HUANG Xiao-jun

    2006-01-01

    @@ Cord blood transplantation (CBT) from unrelated donors has increasingly been performed worldwide during the last decade. The immaturity of lymphocytes in cord blood permits HLA-mismatching between donors and recipients and reduces the severity of graft-versus-host disease (GVHD).However, the relatively small dose of the cord blood nucleated cells is associated with a high frequency of engraftment failure.1-5 But re-transplantation with stem cells from the original donor is impossible.

  4. Establishment of an adherent cell layer from human umbilical cord blood

    Directory of Open Access Journals (Sweden)

    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