Cellular therapy after spinal cord injury using neural progenitor cells

NARCIS (Netherlands)

Vroemen, Maurice

2006-01-01

In this thesis, the possibilities and limitations of cell-based therapies after spinal cord injury are explored. Particularly, the potential of adult derived neural progenitor cell (NPC) grafts to function as a permissive substrate for axonal regeneration was investigated. It was found that syngenic

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

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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...

Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

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Xue-man Lv

2016-01-01

Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells.

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Prabakar, Kamalaveni R; Domínguez-Bendala, Juan; Molano, R Damaris; Pileggi, Antonello; Villate, Susana; Ricordi, Camillo; Inverardi, Luca

2012-01-01

We sought to assess the potential of human cord blood-derived mesenchymal stem cells (CB-MSCs) to derive insulin-producing, glucose-responsive cells. We show here that differentiation protocols based on stepwise culture conditions initially described for human embryonic stem cells (hESCs) lead to differentiation of cord blood-derived precursors towards a pancreatic endocrine phenotype, as assessed by marker expression and in vitro glucose-regulated insulin secretion. Transplantation of these cells in immune-deficient animals shows human C-peptide production in response to a glucose challenge. These data suggest that human cord blood may be a promising source for regenerative medicine approaches for the treatment of diabetes mellitus.

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

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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.

Proliferation extent of CD34+ cells as a key parameter to maximize megakaryocytic differentiation of umbilical cord blood-derived hematopoietic stem/progenitor cells in a two-stage culture protocol

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Javad Hatami

2014-12-01

Full Text Available Co-infusion of ex-vivo generated megakaryocytic progenitors with hematopoietic stem/progenitor cells (HSC/HPC may contribute to a faster platelet recovery upon umbilical cord blood (UCB transplantation. A two stage protocol containing cell expansion and megakaryocyte (Mk differentiation was established using human UCB CD34+-enriched cells. The expansion stage used a pre-established protocol supported by a human bone marrow mesenchymal stem cells (MSC feeder layer and the differentiation stage used TPO (100 ng/mL and IL-3 (10 ng/mL. 18% of culture-derived Mks had higher DNA content (>4 N and were able to produce platelet-like particles. The proliferation extent of CD34+ cells obtained in the expansion stage (FI-CD34+, rather than expansion duration, determined as a key parameter for efficient megakaryocytic differentiation. A maximum efficiency yield (EY of 48 ± 7.7 Mks/input CD34+ cells was obtained for a FI-CD34+ of 17 ± 2.5, where a higher FI-CD34+ of 42 ± 13 resulted in a less efficient megakaryocytic differentiation (EY of 22 ± 6.7 and 19 ± 4.6 %CD41.

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

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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

Pancreas developing markers expressed on human mononucleated umbilical cord blood cells

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Pessina, A.; Eletti, B.; Croera, C.; Savalli, N.; Diodovich, C.; Gribaldo, L.

2004-01-01

Haematopoietic system represents the main source of haematopoietic stem cells and probably of multipotential adult progenitor cells and mesenchimal stem cells at first described as colony forming unit-fibroblast. Whereas there are many studies on the gene expression profile of the different precursors along their haematopoietic differentiation, few data (sometimes conflicting) have been reported about the phenotype of the cells (present in bone marrow and possibly in cord blood) able to differentiate into non-haematopoietic cells. As both postnatal bone marrow and umbilical cord blood contain nestin positive cells able to proliferate and differentiate into the main neural phenotype (neuron, astroglia and oligodendroglia) many authors considered nestin a neuroepithelial precursor marker that seems to be essential also in multipotential progenitor cells of pancreas present both in rat and in human pancreatic islets (called nestin positive islet derived progenitors). Although the importance of nestin in these cells appears to be evident, it remains yet to clarify the number and the sequential expression of the genes coding all the transcription factors essential for beta cells differentiation and therefore the conditions able to induce the expression of many important transcription factors genes such as isl-1, pax-4, pdx-1 and ngn-3. Among them pdx-1 is a gene essential for pancreas development which is able to control ngn-3 in activating the expression of other differentiation factors for endocrine cells. Here, we describe for the first time in human umbilical cord blood cells (UCB) the pattern of expression of a panel of markers (nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) considered important for beta cells differentiation. Our data demonstrate that UCB contains a cell population having a phenotype very similar to endocrine cell precursors in transition to beta cells

Successful in vitro expansion and differentiation of cord blood derived CD34+ cells into early endothelial progenitor cells reveals highly differential gene expression.

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Ingo Ahrens

Full Text Available Endothelial progenitor cells (EPCs can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP, PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15 or pro-angiogenic (galectin-3 properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP was the most up-regulated gene.

Prospect for application of umbilical cord blood to clinical treatment of radiation sickness

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Jia Tingzhen; Ke Xiaoyan

1998-01-01

Objective: To look forward to the prospect for application of umbilical cord blood to clinical treatment of radiation sickness by analyzing the results using umbilical cord blood in laboratory experiments and clinical research. Method: The data on umbilical cord blood published in literature are reviewed. Results: The umbilical blood is rich in hematopoietic stem/progenitor cells, low in immunological activity of lymphocytes, expanded significantly ex vivo under selected culture condition readily available and collected easily. Conclusion: With the above advantages, the prospect for application of umbilical cord blood is encouraging, particularly in the clinical treatment of radiation sickness

PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells.

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Varagnolo, Linda; Lin, Qiong; Obier, Nadine; Plass, Christoph; Dietl, Johannes; Zenke, Martin; Claus, Rainer; Müller, Albrecht M

2015-07-22

Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.

How to improve cord blood engraftment?

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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.

Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion

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Zhao Yong; Mazzone, Theodore

2005-01-01

We have previously characterized a new type of stem cell from human peripheral blood, termed fibroblast-like macrophage (f-MΦ). Here, using umbilical cord blood as a source, we identified cells with similar characteristics including expression of surface markers (CD14, CD34, CD45, CD117, and CD163), phagocytosis, and proliferative capacity. Further, thrombopoietin (TPO) significantly stimulated the proliferation of cord blood-derived f-MΦ (CB f-MΦ) at low dosage without inducing a megakaryocytic phenotype. Additional experiments demonstrated that TPO-expanded cord blood-derived f-MΦ (TCB f-MΦ) retained their surface markers and differentiation ability. Treatment with vascular endothelial cell growth factor (VEGF) gave rise to endothelial-like cells, expressing Flt-1, Flk-1, von Willebrand Factor (vWF), CD31, acetylated low density lipoprotein internalization, and the ability to form endothelial-like cell chains. In the presence of lipopolyssacharide (LPS) and 25 mM glucose, the TCB f-MΦ differentiated to express insulin mRNA, C-peptide, and insulin. In vitro functional analysis demonstrated that these insulin-positive cells could release insulin in response to glucose and other secretagogues. These findings demonstrate a potential use of CB f-MΦ and may lead to develop new therapeutic strategy for treating dominant disease

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

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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

Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

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Zhong-jun Zhang

2015-01-01

Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Cord Blood Chimerism And Relapse After Haplo-Cord Transplantation

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van Besien, Koen; Koshy, Nebu; Gergis, Usama; Mayer, Sebastian; Cushing, Melissa; Rennert, Hannah; Slotky, Ronit; Mark, Tomer; Pearse, Roger; Rossi, Adriana; Phillips, Adrienne; Vasovic, Liljana; Ferrante, Rosanna; Hsu, Michael; Shore, Tsiporah

2018-01-01

Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic GVHD. But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with AML and MDS, engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% vs 11% Pdisease recurrence (46% vs 12%, P=0.007) Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% vs 15%, P=0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful GVL effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high. PMID:27333804

The influence of BDNF on human umbilical cord blood stem/progenitor cells: implications for stem cell-based therapy of neurodegenerative disorders.

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Paczkowska, Edyta; Łuczkowska, Karolina; Piecyk, Katarzyna; Rogińska, Dorota; Pius-Sadowska, Ewa; Ustianowski, Przemysław; Cecerska, Elżbieta; Dołęgowska, Barbara; Celewicz, Zbigniew; Machaliński, Bogusław

2015-01-01

Umbilical cord blood (UCB)-derived stem/progenitor cells (SPCs) have demonstrated the potential to improve neurologic function in different experimental models. SPCs can survive after transplantation in the neural microenvironment and indu ce neuroprotection, endogenous neurogenesis by secreting a broad repertoire of trophic and immunomodulatory cytokines. In this study, the influence of brain-derived neurotrophic factor (BDNF) pre-treatment was comprehensively evaluated in a UCB-derived lineage-negative (Lin-) SPC population. UCB-derived Lin- cells were evaluated with respect to the expression of (i) neuronal markers using immunofluorescence staining and (ii) specific (TrkB) receptors for BDNF using flow cytometry. Next, after BDNF pre-treatment, Lin- cells were extensively assessed with respect to apoptosis using Western blotting and proliferation via BrdU incorporation. Furthermore, NT-3 expression levels in Lin- cells using RQ PCR and antioxidative enzyme activities were assessed. We demonstrated neuronal markers as well as TrkB expression in Lin- cells and the activation of the TrkB receptor by BDNF. BDNF pre-treatment diminished apoptosis in Lin- cells and influenced the proliferation of these cells. We observed significant changes in antioxidants as well as in the increased expression of NT-3 in Lin- cells following BDNF exposure. Complex global miRNA and mRNA profiling analyses using microarray technology and GSEA revealed the differential regulation of genes involved in the proliferation, gene expression, biosynthetic processes, translation, and protein targeting. Our results support the hypothesis that pre-treatment of stem/progenitor cells could be beneficial and may be used as an auxiliary strategy for improving the properties of SPCs.

Cord Blood

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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

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

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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.

Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner.

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Tania J Fernandes

Full Text Available In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and β-glycerophosphate these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM, and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2 actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells

Comparative Analysis of the Hematopoietic Progenitor Cells from Placenta, Cord Blood, and Fetal Liver, Based on Their Immunophenotype

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Maria D. Kuchma

2015-01-01

Full Text Available We have investigated the characteristics of human hematopoietic progenitor cells (HPCs with the CD34+CD45lowSSClow phenotype from full-term placental tissue (FTPT as compared to cord blood (CB and fetal liver (FL cells. We demonstrated the presence of cell subpopulations at various stages of the differentiation with such immunophenotypes as CD34+/lowCD45low/-, CD34++CD45low/-, CD34+++CD45low/-, CD34+/lowCD45hi, and CD34++CD45hi in both first trimester placental tissue (FiTPT and FTPT which implies their higher phenotypic heterogeneity compared to CB. HPCs of the FTPT origin expressed the CD90 antigen at a higher level compared to its expression by the CB HPCs and the CD133 antigen expression being at the same level in both cases. The HPCs compartment of FTPT versus CB contained higher number of myeloid and erythroid committed cells but lower number of myeloid and lymphoid ones compared to FL HPCs. HPCs of the FTPT and CB origin possess similar potentials for the multilineage differentiation in vitro and similar ratios of myeloid and erythroid progenitors among the committed cells. This observation suggests that the active hematopoiesis occurs in the FTPT. We obtained viable HPCs from cryopreserved placental tissue fragments allowing us to develop procedures for banking and testing of placenta-derived HPCs for clinical use.

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells.

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Audigé, Annette; Rochat, Mary-Aude; Li, Duo; Ivic, Sandra; Fahrny, Audrey; Muller, Christina K S; Gers-Huber, Gustavo; Myburgh, Renier; Bredl, Simon; Schlaepfer, Erika; Scherrer, Alexandra U; Kuster, Stefan P; Speck, Roberto F

2017-05-30

Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time. Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice.

Is There Any Reason to Prefer Cord Blood Instead of Adult Donors for Hematopoietic Stem Cell Transplants?

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Beksac, Meral

2015-01-01

As cord blood (CB) enables rapid access and tolerance to HLA mismatches, a number of unrelated CB transplants have reached 30,000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified cord blood units (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 CB transplants success by decreasing transplant-related mortality. CB progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to bone marrow-mesenchymal stromal cells and lesser oncogenic potential than progenitor-induced stem cells. This chapter summarizes the advantages and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

Umbilical Cord Blood: Counselling, Collection, and Banking.

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

2015-09-01

bone marrow or peripheral stem cell transplantation to treat malignant and non-malignant conditions in children and adults. There is minimal harm to the mother or newborn provided that priority is given to maternal/newborn safety during childbirth management. Recipients of umbilical cord stem cells may experience graft-versus-host disease, transfer of infection or genetic abnormalities, or therapeutic failure. The financial burden on the health system for public cord blood banking and on families for private cord blood banking is considerable. Recommendations 1. Health care professionals should be well-informed about cord blood collection and storage and about factors that influence the volume, quality, and ability to collect a cord blood unit. (III-A) 2. Health care professionals caring for women and families who choose private umbilical cord blood banking must disclose any financial interests or potential conflicts of interest. (III-A) 3. Pregnant women should be provided with unbiased information about umbilical cord blood banking options, including the benefits and limitations of public and private banks. (III-A) 4. Health care professionals should obtain consent from mothers for the collection of umbilical cord blood prior to the onset of active labour, ideally during the third trimester, with ample time to address any questions. (III-A) 5. Health care professionals must be trained in standardized procedures (ex utero and in utero techniques) for cord blood collection to ensure the sterility and quality of the collected unit. (II-2A) 6. Umbilical cord blood should be collected with the goal of maximizing the content of hematopoietic progenitors through the volume collected. The decision to bank the unit will depend upon specific measures of graft potency. (II-2A) 7. Umbilical cord blood collection must not adversely affect the health of the mother or newborn. Cord blood collection should not interfere with delayed cord clamping. (III-E) 8. Health care

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

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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.

Cord Blood and Transplants

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... donate their baby’s umbilical cord blood to a public cord blood bank. We have more than 249,000 cord blood ... stored as a cord blood unit at a public cord blood bank for future use. It can then be listed ...

Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors

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Avanzini, Maria Antonietta; Bernardo, Maria Ester; Cometa, Angela Maria; Perotti, Cesare; Zaffaroni, Nadia; Novara, Francesca; Visai, Livia; Moretta, Antonia; Del Fante, Claudia; Villa, Raffaella; Ball, Lynne M.; Fibbe, Willem E.; Maccario, Rita; Locatelli, Franco

2009-01-01

Background Mesenchymal stromal cells are employed in various different clinical settings in order to modulate immune response. However, relatively little is known about the mechanisms responsible for their immunomodulatory effects, which could be influenced by both the cell source and culture conditions. Design and Methods We tested the ability of a 5% platelet lysate-supplemented medium to support isolation and ex vivo expansion of mesenchymal stromal cells from full-term umbilical-cord blood. We also investigated the biological/functional properties of umbilical cord blood mesenchymal stromal cells, in comparison with platelet lysate-expanded bone marrow mesenchymal stromal cells. Results The success rate of isolation of mesenchymal stromal cells from umbilical cord blood was in the order of 20%. These cells exhibited typical morphology, immunophenotype and differentiation capacity. Although they have a low clonogenic efficiency, umbilical cord blood mesenchymal stromal cells may possess high proliferative potential. The genetic stability of these cells from umbilical cord blood was demonstrated by a normal molecular karyotype; in addition, these cells do not express hTERT and telomerase activity, do express p16ink4a protein and do not show anchorage-independent cell growth. Concerning alloantigen-specific immune responses, umbilical cord blood mesenchymal stromal cells were able to: (i) suppress T- and NK-lymphocyte proliferation, (ii) decrease cytotoxic activity and (iii) only slightly increase interleukin-10, while decreasing interferon-γ secretion, in mixed lymphocyte culture supernatants. While an indoleamine 2,3-dioxygenase-specific inhibitor did not reverse mesenchymal stromal cell-induced suppressive effects, a prostaglandin E2-specific inhibitor hampered the suppressive effect of both umbilical cord blood- and bone marrow-mesenchymal stromal cells on alloantigen-induced cytotoxic activity. Mesenchymal stromal cells from both sources expressed HLA

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

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Sharyn L Rossi

2010-07-01

Full Text Available Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit.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.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.

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

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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.

Impact of C-rel inhibition of cord blood-derived B-, T-, and NK cells.

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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

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

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

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/m(2), 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 CD45(dim) blast gate). The proportion of CD34(+)CD45(dim) HSPCs among the nucleated cells was significantly (P mothers with GDM (median 0.38%) compared to neonates born to nondiabetic mothers (median 0.32%) and according to treatment types (P 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.

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

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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.

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

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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.

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

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Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (Pin the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (Pin the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

Recombinant TAT-BMI-1 fusion protein induces ex vivo expansion of human umbilical cord blood-derived hematopoietic stem cells.

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Codispoti, Bruna; Rinaldo, Nicola; Chiarella, Emanuela; Lupia, Michela; Spoleti, Cristina Barbara; Marafioti, Maria Grazia; Aloisio, Annamaria; Scicchitano, Stefania; Giordano, Marco; Nappo, Giovanna; Lucchino, Valeria; Moore, Malcolm A S; Zhou, Pengbo; Mesuraca, Maria; Bond, Heather Mandy; Morrone, Giovanni

2017-07-04

Transplantation of hematopoietic stem cells (HSCs) is a well-established therapeutic approach for numerous disorders. HSCs are typically derived from bone marrow or peripheral blood after cytokine-induced mobilization. Umbilical cord blood (CB) represents an appealing alternative HSC source, but the small amounts of the individual CB units have limited its applications. The availability of strategies for safe ex vivo expansion of CB-derived HSCs (CB-HSCs) may allow to extend the use of these cells in adult patients and to avoid the risk of insufficient engraftment or delayed hematopoietic recovery.Here we describe a system for the ex vivo expansion of CB-HSCs based on their transient exposure to a recombinant TAT-BMI-1 chimeric protein. BMI-1 belongs to the Polycomb family of epigenetic modifiers and is recognized as a central regulator of HSC self-renewal. Recombinant TAT-BMI-1 produced in bacteria was able to enter the target cells via the HIV TAT-derived protein transduction peptide covalently attached to BMI-1, and conserved its biological activity. Treatment of CB-CD34+ cells for 3 days with repeated addition of 10 nM purified TAT-BMI-1 significantly enhanced total cell expansion as well as that of primitive hematopoietic progenitors in culture. Importantly, TAT-BMI-1-treated CB-CD34+ cells displayed a consistently higher rate of multi-lineage long-term repopulating activity in primary and secondary xenotransplants in immunocompromised mice. Thus, recombinant TAT-BMI-1 may represent a novel, effective reagent for ex vivo expansion of CB-HSC for therapeutic purposes.

Awareness of cord blood banking among pregnant women in semi urban area

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Poomalar G. K.; Jayasree M.

2016-01-01

Background: Hematopoietic stem cells (HSCs) are multipotent stem cells, derived from bone marrow, peripheral blood and umbilical cord. These HSC are accepted method of treatment for various disorders. Cord blood can be stored either in private or public bank. Awareness about cord blood banking among semi urban and rural population is less compared to urban population. The aim of our study is to evaluate the awareness of cord blood banking among pregnant women in semi urban area and to evaluat...

Carlecortemcel-l: an ex vivo expanded umbilical cord blood cell graft for allogeneic transplantation.

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Petropoulos, Demetrios; Chan, Ka Wah

2009-11-01

Success of umbilical cord blood transplantation (UCBT) is mostly affected by the cell dose infused and its application is limited by the size of the recipient. For most adults and older children it is not possible to find a single UCB unit large enough for reliable engraftment. One strategy to increase the number of progenitor cells available is ex vivo expansion of the unit. The main challenge of ex vivo expansion systems is how not to deplete the self-renewing cell population by driving them into differentiation into committed progenitors. Copper modulates basic cell functions, such as survival, proliferation, and differentiation. Reduction of cellular copper in ex vivo culture conditions enabled preferential proliferation of early progenitors and increased engraftment capabilities. The result of a Phase I study of carlecortemcel-l, a product derived from ex vivo expansion of UCB progenitors in the presence of a copper chelator and early-acting cytokines, and the study design for the current pivotal study are presented. A literature review using PubMed and the investigator's brochure from the manufacturer. Early results suggest that carlecortemcel-l infusion is safe and may be associated with favorable non-relapse mortality rates. A pivotal global study is currently being conducted to evaluate safety and efficacy of this product from centralized manufacturing facilities.

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation.

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Dou, John; Schmidt, Rebecca J; Benke, Kelly S; Newschaffer, Craig; Hertz-Picciotto, Irva; Croen, Lisa A; Iosif, Ana-Maria; LaSalle, Janine M; Fallin, M Daniele; Bakulski, Kelly M

2018-01-01

Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (P PC1 = 1.4 × 10 -9 ; P PC2 = 2.9 × 10 -5 ; P PC3 = 3.8 × 10 -5 ; P PC4 = 4.2 × 10 -6 ; P PC5 = 9.9 × 10 -13 , P PC6 = 1.3 × 10 -11 ) and not with sample type (P PC1-6 >0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted Pcoat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

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Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

2011-01-01

The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank.

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Bassiouny, M R; El-Chennawi, F; Mansour, A K; Yahia, S; Darwish, A

2015-06-01

Umbilical cord blood (UCB) contains stem cells and can be used as an alternative to bone marrow transplantation. Engraftment is dependent on the total nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study was designed to evaluate the effect of the method of collection of the UCB on the yield of the cord blood units. Informed consent was obtained from 100 eligible mothers for donation of cord blood. Both in utero and ex utero methods were used for collection. The cord blood volume was measured. The TNC and the CD34+ cell counts were enumerated. We have found that in utero collection gave significantly larger volumes of cord blood and higher TNC counts than ex utero collection. There was no significant difference between both methods regarding the CD34+ cell counts. This study revealed a significant correlation between the volume of the collected cord blood and both TNC and CD34+ cell counts. It is better to collect cord blood in utero before placental delivery to optimize the quality of the cord blood unit. © 2015 AABB.

Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

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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.

Low antigenicity of hematopoietic progenitor cells derived from human ES cells

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Eun-Mi Kim

2010-02-01

Full Text Available Eun-Mi Kim1, Nicholas Zavazava1,21Department of Internal Medicine, University of Iowa and Veterans Affairs Medical Center, Iowa City, Iowa, USA; 2Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USAAbstract: Human embryonic stem (hES cells are essential for improved understanding of diseases and our ability to probe new therapies for use in humans. Currently, bone marrow cells and cord blood cells are used for transplantation into patients with hematopoietic malignancies, immunodeficiencies and in some cases for the treatment of autoimmune diseases. However, due to the high immunogenicity of these hematopoietic cells, toxic regimens of drugs are required for preconditioning and prevention of rejection. Here, we investigated the efficiency of deriving hematopoietic progenitor cells (HPCs from the hES cell line H13, after co-culturing with the murine stromal cell line OP9. We show that HPCs derived from the H13 ES cells poorly express major histocompatibility complex (MHC class I and no detectable class II antigens (HLA-DR. These characteristics make hES cell-derived hematopoietic cells (HPCs ideal candidates for transplantation across MHC barriers under minimal immunosuppression.Keywords: human embryonic stem cells, H13, hematopoiesis, OP9 stromal cells, immunogenicity

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.

Incorporating placental tissue in cord blood banking for stem cell transplantation.

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Teofili, Luciana; Silini, Antonietta R; Bianchi, Maria; Valentini, Caterina Giovanna; Parolini, Ornella

2018-06-01

Human term placenta is comprised of various tissues from which different cell populations can be obtained, including hematopoietic stem cells and mesenchymal stem/stromal cells (MSCs). Areas covered: This review will discuss the possibility to incorporate placental tissue cells in cord blood banking. It will discuss general features of human placenta, with a brief review of the immune cells at the fetal-maternal interface and the different cell populations isolated from placenta, with a particular focus on MSCs. It will address the question as to why placenta-derived MSCs should be banked with their hematopoietic counterparts. It will discuss clinical trials which are studying safety and efficacy of placenta tissue-derived MSCs in selected diseases, and preclinical studies which have proven their therapeutic properties in other diseases. It will discuss banking of umbilical cord blood and raise several issues for improvement, and the applications of cord blood cells in non-malignant disorders. Expert Commentary: Umbilical cord blood banking saves lives worldwide. The concomitant banking of non-hematopoietic cells from placenta, which could be applied therapeutically in the future, alone or in combination to their hematopoietic counterparts, could exploit current banking processes while laying the foundation for clinical trials exploring placenta-derived cell therapies in regenerative medicine.

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

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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.

Microbial contamination of the Tzu-Chi Cord Blood Bank from 2005 to 2006.

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Chen, Shu-Huey; Zheng, Ya-Jun; Yang, Shang-Hsien; Yang, Kuo-Liang; Shyr, Ming-Hwang; Ho, Yu-Huai

2008-01-01

In total, 4502 units of cord blood (CB) were collected during a 2-year period from 2005 to 2006 by the Buddhist Tzu-Chi Stem Cells Center. The aim of this study was to analyze the incidence of microbial contamination and type of organism present in the cord blood. The clinical impact of microbial contamination on hematopoietic progenitor cell (HPC) grafts used for HPC transplantation is also discussed. First and second specimens were obtained for microbial assessment. These were collected in laboratory after cord blood collection and after cord blood unit manipulation, respectively. The samples were cultured and the results reviewed. The overall incidence of microbiological contamination was 1.8% (82/4502). Three CB units were contaminated with two different organisms. Infectious organisms comprised 9.4% (8/85) of total isolated microbes. These infectious microorganisms were beta-Streptococci group B, Candida tropicalis and Staphylococcus aureus which were isolated in 6, 1 and 1 of CB units respectively. Escherichia coli, Bacteroides fragilis, Lactobacillus spp., Enterococcus, beta-Streptococcus Group B, Bacteroides valgatus, Corynebacterium spp., Klebsiella pneumonia and Peptococcus spp. were the most frequently encountered microorganisms. A higher contamination rate of the CB units was noted after vaginal delivery (2.16%) compared to caesarian section (0.85%) (p bank, we use a closed system but an in utero method. Similar to other studies, most of microorganisms reported here as contaminants are non-pathogenic.

Short-term, serum-free, static culture of cord blood-derived CD34+ cells: effects of FLT3-L and MIP-1alpha on in vitro expansion of hematopoietic progenitor cells.

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Capmany, G; Querol, S; Cancelas, J A; García, J

1999-08-01

The use of ex vivo expanded cells has been suggested as a possible means to accelerate the speed of engraftment in cord blood (CB) transplantation. The aim of this study was to fix the optimal condition for the generation of committed progenitors without affecting the stem cell compartment. Analysis of the effects of FLT3-L and MIP-1alpha when combined with SCF, IL-3 and IL-6, in short-term (6 days), serum-free expansion cultures of CB-selected CD34+ cells. An important expansion was obtained that ranged between 8-15 times for CFU-GM, 21-51 times for the BFU-E/CFU-Mix population and 11 to 30 times for CD34+ cells assessed by flow cytometry. From the combinations tested, those in which FLT3-L was present had a significant increase in the expansion of committed progenitors, while the presence of MIP-1alpha had a detrimental effect on the generation of more differentiated cells. However, stem cell candidates assessed by week 5 CAFC assay could be maintained in culture when both MIP-1a and FLT3-L were present (up to 91% recovery). This culture system was also able to expand megakaryocytic precursors as determined by the co-expression of CD34 and CD61 antigens (45-70 times), in spite of the use of cytokines non-specific for the megakaryocytic lineage. The results obtained point to the combination of SCF, IL-3, IL-6, FLT3-L and MIP-1alpha as the best suited for a pre-clinical short-term serum-free static ex vivo expansion protocol of CB CD34+ cells, since it can generate large numbers of committed progenitor cells as well as maintaining week 5 CAFC.

Umbilical Cord Blood-Derived Stem Cells Improve Heat Tolerance and Hypothalamic Damage in Heat Stressed Mice

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Ling-Shu Tseng

2014-01-01

Full Text Available Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour and then returned to room temperature (26°C for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C. Four hours after termination of heat stress, heated mice displayed (i systemic inflammation; (ii ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone; (iv decreased fractional survival; and (v thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature. These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34+ cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

Cord Blood Banking for Potential Future Transplantation.

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Shearer, William T; Lubin, Bertram H; Cairo, Mitchell S; Notarangelo, Luigi D

2017-11-01

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

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Hayato Fukusumi

2016-01-01

Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications.

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Baron, Frédéric; Ruggeri, Annalisa; Nagler, Arnon

2016-03-01

More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low absolute numbers of hematopoietic stem and progenitor cells (HSPCs) within a single cord blood unit has remained a limiting factor for this transplantation modality, particularly in adult recipients. Further, because UCB contains low numbers of mostly naïve T cells, immune recovery after UCBT is slow, predisposing patients to severe infections. Other causes of UCBT failure has included graft-versus-host disease (GVHD) and relapse of the underlying disease. In this article, we first review the current landscape of cord blood engineering aimed at improving engraftment. This includes approaches of UCB-HSPCs expansion and methods aimed at improving UCB-HSCPs homing. We then discuss recent approaches of cord blood engineering developed to prevent infection [generation of multivirus-specific cytotoxic T cells (VSTs) from UCB], relapse [transduction of UCB-T cells with tumor-specific chimeric receptor antigens (CARs)] and GVHD (expansion of regulatory T cells from UCB). Although many of these techniques of UCB engineering remain currently technically challenging and expensive, they are likely to revolutionize the field of UCBT in the next decades.

Optimization of the culturing conditions of human umbilical cord blood-derived endothelial colony-forming cells under xeno-free conditions applying a transcriptomic approach

NARCIS (Netherlands)

Zeisberger, Steffen M.; Zoller, Stefan; Riegel, Mariluce; Chen, Shuhua; Krenning, Guido; Harmsen, Martin C.; Sachinidis, Agapios; Zisch, Andreas H.

Establishment of fetal bovine serum (FBS)-free cell culture conditions is essential for transplantation therapies. Blood-derived endothelial colony-forming cells (ECFCs) are potential candidates for regenerative medicine applications. ECFCs were isolated from term umbilical cord blood units and

Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping

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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.

Umbilical cord blood for unrelated bone marrow replacement; Asia bank and Japan cord blood bank network update.

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Mugishima, Hideo; Takahashi, Tuneo; Nagamura, Tokiko; Asano, Sigetaka; Saito, Hidehiko

2002-08-01

Cord blood offers many advantages including a high concentration of hematopoietic stem cells, a large number of potential donors, and ease of harvest. Furthermore, since there is no risk for either the mother or baby, few people refuse to donate. There is thought to be a low risk for virus contamination and also probably a low incidence and severity of GVHD. Cord blood can be obtained quickly without the assistance of a coordinator and one or 2 locus-mismatched HLA is usually acceptable. In Japan, there are 10 cord blood banks supported by the government. Between 1996 and June 2002, 9,500 units were registered with the Japan cord blood bank network (JCBBN). 630 units were delivered and most of these were transplanted. The status of registered cord blood units worldwide is shown. 59,081 units have been registered by NETCORD. The Japan cord blood bank network accounts for 13% of these units. I will discuss the Tokyo cord blood tank (TCBB). The bank at Tokyo, to which we belong, is one of the largest banks in Japan. We helped to establish Asia CORD in 2000 and have held annual conferences and meetings in Tokyo to exchange information. So far, China, Korea, Taiwan, Thailand, Viet Nam and Japan have participated. We accepted three trainees from the Ho Chi Minh City Blood Transfusion and Hematology Center for training in cord blood transplantation in May 2001. In January 2002, a patient with ALL received cord blood and was successfully engrafted at Ho Chi Minh City Blood Transfusion and Hematology Center. We present here the clinical outcome of these patients through Tokyo cord blood bank and Japan cord blood bank network. First, the number of CB units stored and registered at JCBBN and TCBB has increased rapidly over the past two years. Second, the survival rate of acute leukemia patients in release was significantly lower than that in patients in CR. Third, the engraftment rate in patients with metabolic disease (50%) was lower than that in patients with leukemia

Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture.

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Bakhshi, Tiki; Zabriskie, Ryan C; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A; Gregory, Stephanie A; Fung, Henry C; Christopherson, Kent W

2008-12-01

Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. Umbilical cord-derived MSCs (UC-MSCs) were cultured from the Wharton's jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. These data suggest the potential therapeutic application of Wharton's jelly-derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.

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

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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.

Family-directed umbilical cord blood banking.

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

2011-11-01

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.

Alcohol Enhances HIV Infection of Cord Blood Monocyte-Derived Macrophages

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Mastrogiannis, Dimitrios S.; Wang, Xu; Dai, Min; Li, Jieliang; Wang, Yizhong; Zhou, Yu; Sakarcan, Selin; Peña, Juliet Crystal; Ho, Wenzhe

2014-01-01

Alcohol consumption or alcohol abuse is common among pregnant HIV+ women and has been identified as a potential behavioral risk factor for the transmission of HIV. In this study, we examined the impact of alcohol on HIV infection of cord blood monocyte-derived macrophages (CBMDM). We demonstrated that alcohol treatment of CBMDM significantly enhanced HIV infection of CBMDM. Investigation of the mechanisms of alcohol action on HIV demonstrated that alcohol inhibited the expression of several HIV restriction factors, including anti-HIV microRNAs, APOBEC3G and APOBEC3H. Additionally, alcohol also suppressed the expression of IFN regulatory factor 7 (IRF-7) and retinoic acid-inducible gene I (RIG-I), an intracellular sensor of viral infection. The suppression of these IFN regulatory factors was associated with reduced expression of type I IFN. These experimental findings suggest that maternal alcohol consumption may facilitate HIV infection, promoting vertical transmission of HIV. PMID:25053361

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

OpenAIRE

Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

2016-01-01

Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

Directly measuring spinal cord blood flow and spinal cord perfusion pressure via the collateral network: correlations with changes in systemic blood pressure.

Science.gov (United States)

Kise, Yuya; Kuniyoshi, Yukio; Inafuku, Hitoshi; Nagano, Takaaki; Hirayasu, Tsuneo; Yamashiro, Satoshi

2015-01-01

During thoracoabdominal surgery in which segmental arteries are sacrificed over a large area, blood supply routes from collateral networks have received attention as a means of avoiding spinal cord injury. The aim of this study was to investigate spinal cord blood supply through a collateral network by directly measuring spinal cord blood flow and spinal cord perfusion pressure experimentally. In beagle dogs (n = 8), the thoracoabdominal aorta and segmental arteries L1-L7 were exposed, and a temporary bypass was created for distal perfusion. Next, a laser blood flow meter was placed on the spinal dura mater in the L5 region to measure the spinal cord blood flow. The following were measured simultaneously when the direct blood supply from segmental arteries L2-L7 to the spinal cord was stopped: mean systemic blood pressure, spinal cord perfusion pressure (blood pressure within the aortic clamp site), and spinal cord blood flow supplied via the collateral network. These variables were then investigated for evidence of correlations. Positive correlations were observed between mean systemic blood pressure and spinal cord blood flow during interruption of segmental artery flow both with (r = 0.844, P flow with and without distal perfusion (r = 0.803, P network from outside the interrupted segmental arteries, and high systemic blood pressure (∼1.33-fold higher) was needed to obtain the preclamping spinal cord blood flow, whereas 1.68-fold higher systemic blood pressure was needed when distal perfusion was halted. Spinal cord blood flow is positively correlated with mean systemic blood pressure and spinal cord perfusion pressure under spinal cord ischemia caused by clamping a wide range of segmental arteries. In open and endovascular thoracic and thoracoabdominal surgery, elevating mean systemic blood pressure is a simple and effective means of increasing spinal cord blood flow, and measuring spinal cord perfusion pressure seems to be useful for monitoring

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.

[Prenatal lead exposure related to cord blood brain derived neurotrophic factor (BDNF) levels and impaired neonatal neurobehavioral development].

Science.gov (United States)

Ren, L H; Mu, X Y; Chen, H Y; Yang, H L; Qi, W

2016-06-01

To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 μmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 μmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. Lead content in high exposure group was (0.613±0.139) μmol/L, and higher than (0.336±0.142) μmol/L in low exposure group (t=3.21, PBDNF content in high exposure group which was (3.538±1.203) ng/ml was higher than low exposure group (2.464±0.918) ng/ml (t=7.60, PBDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.

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

culturing resulted in a multicellular layer tissue with formation of more cartilaginous tissue compared to micromass or CPP culture. In the membrane system MLPCs produced pellucid discs, 12 mm in diameter by 1 mm in thickness from 2x10^6 cells. The discs had hyaline-like cartilage extracellular matrix......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...... with micromass or CPP cultures. Conclusions: In conclusion, we demonstrate that MLPCs possess’ chondrogenic potency, which increased when cultured scaffold-free on membrane inserts resulting in multicellular-layered hyaline-like cartilage tissue. Evaluating the effect of culturing pre-differentiated MLPCs on CPP...

A Novel Method for Isolation of Pluripotent Stem Cells from Human Umbilical Cord Blood.

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Monti, Manuela; Imberti, Barbara; Bianchi, Niccolò; Pezzotta, Anna; Morigi, Marina; Del Fante, Claudia; Redi, Carlo Alberto; Perotti, Cesare

2017-09-01

Very small embryonic-like cells (VSELs) are a population of very rare pluripotent stem cells isolated in adult murine bone marrow and many other tissues and organs, including umbilical cord blood (UCB). VSEL existence is still not universally accepted by the scientific community, so for this purpose, we sought to investigate whether presumptive VSELs (pVSELs) could be isolated from human UCB with an improved protocol based on the isolation of enriched progenitor cells by depletion of nonprogenitor cells with magnetic separation. Progenitor cells, likely including VSELs, cultured with retinoic acid were able to form dense colonies and cystic embryoid bodies and to differentiate toward the ecto-meso-endoderm lineages as shown by the positivity to specific markers. VSEL differentiative potential toward mesodermal lineage was further demonstrated in vitro upon exposure to an established inductive protocol, which induced the acquisition of renal progenitor cell phenotype. VSEL-derived renal progenitors showed regenerative potential in a cisplatin model of acute kidney injury by restoring renal function and tubular structure through induction of proliferation of endogenous renal cells. The data presented here foster the great debate that surrounds VSELs and, more in general, the existence of cells endowed with pluripotent features in adult tissues. In fact, the possibility to find and isolate subpopulations of cells that fully fit all the criteria utilized to define pluripotency remains, nowadays, almost unproven. Thus, efforts to better characterize the phenotype of these intriguing cells are crucial to understand their possible applications for regenerative and precision medicine purposes.

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

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Naimisha Beeravolu

2016-05-01

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

Religious perspectives on umbilical cord blood banking.

Science.gov (United States)

Jordens, Christopher F C; O'Connor, Michelle A C; Kerridge, Ian H; Stewart, Cameron; Cameron, Andrew; Keown, Damien; Lawrence, Rabbi Jeremy; McGarrity, Andrew; Sachedina, Abdulaziz; Tobin, Bernadette

2012-03-01

Umbilical cord blood is a valuable source of haematopoietic stem cells. There is little information about whether religious affiliations have any bearing on attitudes to and decisions about its collection, donation and storage. The authors provided information about umbilical cord blood banking to expert commentators from six major world religions (Catholicism, Anglicanism, Islam, Judaism, Hinduism and Buddhism) and asked them to address a specific set of questions in a commentary. The commentaries suggest there is considerable support for umbilical cord blood banking in these religions. Four commentaries provide moral grounds for favouring public donation over private storage. None attach any particular religious significance to the umbilical cord or to the blood within it, nor place restrictions on the ethnicity or religion of donors and recipients. Views on ownership of umbilical cord blood vary. The authors offer a series of general points for those who seek a better understanding of religious perspectives on umbilical cord blood banking.

Banking on cord blood stem cells.

Science.gov (United States)

Sullivan, Michael J

2008-07-01

Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

Evaluation of motor neuron differentiation potential of human umbilical cord blood- derived mesenchymal stem cells, in vitro.

Science.gov (United States)

Yousefi, Behnam; Sanooghi, Davood; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Latifi, Nourahmad

2017-04-01

Many people suffer from spinal cord injuries annually. These deficits usually threaten the quality of life of patients. As a postpartum medically waste product, human Umbilical Cord Blood (UCB) is a rich source of stem cells with self- renewal properties and neural differentiation capacity which made it useful in regenerative medicine. Since there is no report on potential of human umbilical cord blood-derived mesenchymal stem cells into motor neurons, we set out to evaluate the differentiation properties of these cells into motor neuron-like cells through administration of Retinoic Acid(RA), Sonic Hedgehog(Shh) and BDNF using a three- step in vitro procedure. The results were evaluated using Real-time PCR, Flowcytometry and Immunocytochemistry for two weeks. Our data showed that the cells changed into bipolar morphology and could express markers related to motor neuron; including Hb-9, Pax-6, Islet-1, NF-H, ChAT at the level of mRNA and protein. We could also quantitatively evaluate the expression of Islet-1, ChAT and NF-H at 7 and 14days post- induction using flowcytometry. It is concluded that human UCB-MSCs is potent to express motor neuron- related markers in the presence of RA, Shh and BDNF through a three- step protocol; thus it could be a suitable cell candidate for regeneration of motor neurons in spinal cord injuries. Copyright © 2017. Published by Elsevier B.V.

Clinical Use and Patentability of Cord Blood

Science.gov (United States)

Cavusoglu, Turker; Kilic, Kubilay Dogan; Yigitturk, Gurkan; Tomruk, Canberk; Turgut, Mehmet; Uyanikgil, Yigit

2018-03-14

The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and au-tologous usage, the most important disadvantage is that the number of cells is insufficient in adults. Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture

Science.gov (United States)

Bakhshi, Tiki; Zabriskie, Ryan C.; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A.; Gregory, Stephanie A.; Fung, Henry C.; Christopherson, Kent W.

2012-01-01

BACKGROUND Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow–derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton’s jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. STUDY DESIGN AND METHODS Umbilical cord–derived MSCs (UC-MSCs) were cultured from the Wharton’s jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. RESULTS Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. CONCLUSION These data suggest the potential therapeutic application of Wharton’s jelly–derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation. PMID:18798803

Opportunities and Challenges for Repair of Macrovascular Disease using Circulating Blood-Derived Progenitor Cells

OpenAIRE

Loeken, Mary R.

2014-01-01

There are currently few solutions for diabetic vascular disease that involve repair of damaged tissues. The manuscript by Porat, et al., suggests a possible method to use a patient’s own circulating blood cells to provide progenitors to repair damaged vascular tissues.

Haemopoietic progenitor cells in human peripheral blood

International Nuclear Information System (INIS)

Zwaan, F.E.

1980-01-01

The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries.

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Çil, N; Oğuz, E O; Mete, E; Çetinkaya, A; Mete, G A

2017-01-01

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.

Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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Takayuki Kondo

2014-08-01

Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

Cord blood banking and transplantation: advances and controversies.

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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.

Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

International Nuclear Information System (INIS)

Otsuru, Satoru; Tamai, Katsuto; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

2007-01-01

Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood

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

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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.

Umbilical cord bloods hematopoietic stem cells ex vivo expansion (the literature review

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T. V. Shamanskaya

2012-01-01

Full Text Available Umbilical cord blood (CB is now an attractive source of hematopoietic stem cells (HSCs for transplantation in pediatric and adult patients with various malignant and non-malignant diseases. However, its clinical application is limited by low cells numbers in graft, which correlates with delayed engraftment, an extension of time to platelets and neutrophils recovery and increasing risk of infectious complications. Several strategies have been suggested to overcome this limitation, one of which is obtaining a sufficient number of hematopoietic progenitor cells by ex vivo expansion. Literature review about CB HSCs expansion in given article is presented.

Migratory capabilities of human umbilical cord blood-derived neural stem cells (HUCB-NSC) in vitro.

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Janowski, Miroslaw; Lukomska, Barbara; Domanska-Janik, Krystyna

2011-01-01

Many types of neural progenitors from various sources have been evaluated for therapy of CNS disorders. Prerequisite for success in cell therapy is the ability for transplanted cells to reach appropriate target such as stroke lesion. We have established neural stem cell line from human umbilical cord blood neural stem (HUCB-NSC). In the present study we evaluated migratory capabilities of cells (HUCB-NSC) and the presence of various migration-related receptors. Immunocytochemical analysis revealed abundant expression of CXCR4, PDGFR-alpha, PDGFR-beta, c-Met, VEGFR, IGF-1R and PSA-NCAM receptors in non-adherent population of HUCB-NSC cultured in serum free (SF) conditions (SF cells). Biological activity of selected receptors was confirmed by HUCB-NSC in vitro migration towards SDF-1 and IGF-1 ligands. Additionally, rat brain-derived homogenates have been assessed for their chemoattractive activity of HUCB-NSC. Our experiments unveiled that brain tissue was more attracted for HUCB-NSC than single ligands with higher potency of injured than intact brain. Moreover, adherent HUCB-NSC cultured in low serum (LS) conditions (LS cells) were employed to investigate an impact of different extracellular matrix (ECM) proteins on cell motility. It turned out that laminin provided most permissive microenvironment for cell migration, followed by fibronectin and gelatin. Unexpected nuclear localization of CXCR4 in SF cells prompted us to characterize intracellular pattern of this expression in relation to developmental stage of cells cultured in different conditions. Continuous culture of LS cells revealed cytoplasmatic pattern of CXCR4 expression while HUCB-NSC cultured in high serum conditions (HS cells) resulted in gradual translocation of CXCR4 from nucleus to cytoplasm and then to arising processes. Terminal differentiation of HUCB-NSC was followed by CXCR4 expression decline.

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.

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Vivanti, Alexandre; Soheili, Tayebeh S; Cuccuini, Wendy; Luce, Sonia; Mandelbrot, Laurent; Lechenadec, Jerome; Cordier, Anne-Gael; Azria, Elie; Soulier, Jean; Cavazzana, Marina; Blanche, Stéphane; André-Schmutz, Isabelle

2015-07-17

Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero. We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively). The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs. Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups. Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.

Neural progenitor cells but not astrocytes respond distally to thoracic spinal cord injury in rat models

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Tara Nguyen

2017-01-01

Full Text Available Traumatic spinal cord injury (SCI is a detrimental condition that causes loss of sensory and motor function in an individual. Many complex secondary injury cascades occur after SCI and they offer great potential for therapeutic targeting. In this study, we investigated the response of endogenous neural progenitor cells, astrocytes, and microglia to a localized thoracic SCI throughout the neuroaxis. Twenty-five adult female Sprague-Dawley rats underwent mild-contusion thoracic SCI (n = 9, sham surgery (n = 8, or no surgery (n = 8. Spinal cord and brain tissues were fixed and cut at six regions of the neuroaxis. Immunohistochemistry showed increased reactivity of neural progenitor cell marker nestin in the central canal at all levels of the spinal cord. Increased reactivity of astrocyte-specific marker glial fibrillary acidic protein was found only at the lesion epicenter. The number of activated microglia was significantly increased at the lesion site, and activated microglia extended to the lumbar enlargement. Phagocytic microglia and macrophages were significantly increased only at the lesion site. There were no changes in nestin, glial fibrillary acidic protein, microglia and macrophage response in the third ventricle of rats subjected to mild-contusion thoracic SCI compared to the sham surgery or no surgery. These findings indicate that neural progenitor cells, astrocytes and microglia respond differently to a localized SCI, presumably due to differences in inflammatory signaling. These different cellular responses may have implications in the way that neural progenitor cells can be manipulated for neuroregeneration after SCI. This needs to be further investigated.

Renal blood flow and oxygenation drive nephron progenitor differentiation.

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Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

2014-08-01

During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

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

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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.

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

. 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 38.5o......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...

[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.

Apolipoprotein E in umbilical cord blood plasma

International Nuclear Information System (INIS)

Forte, T.M.; Davis, P.A.; Blum, C.B.

1983-01-01

Adolipoprotein E (apo E), with a molecular weight of approximately 37,000 daltons, is a minor apolipoprotein constituent in adult plasma lipoproteins. This apolipoprotein, like apolipoprotein B, is a ligand recognized by specific lipoprotein receptor sites (B-E receptors) on cell surfaces. We have recently shown that a pronounced apo E band appears in umbilical cord blood low-density (LDL) lipoproteins and also in high density (HDL) lipoproteins. Densitometric scans of Coomassie blue G-250 stained polyacrylamide gels suggested that apo E was probably elevated in cord blood lipoproteins. To pursue this suggestion, apo E in cord blood was quantitated by radioimmunoassay and correlated with cord blood lipid levels. In addition, apo E levels in 20 normal adult volunteers were also examined

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.

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

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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. Copyright © 2013 Wiley Periodicals, Inc.

Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.

Science.gov (United States)

Requejo-Aguilar, Raquel; Alastrue-Agudo, Ana; Cases-Villar, Marta; Lopez-Mocholi, Eric; England, Richard; Vicent, María J; Moreno-Manzano, Victoria

2017-01-01

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thrombin activatable fibrinolysis inhibitor (TAFI in cord blood.

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Krzysztof Góralczyk

2007-03-01

Full Text Available Thrombin activatable fibrinolysis inhibitor (TAFI is a plasma zymogene (procarboxypeptidase B which can decrease fibrinolysis and thus act as a haemostatic factor. TAFI is now extensively studied in many complications as well as in physiological and complicated pregnancy. The question we posed in the present study was whether TAFI antigen is present in cord blood plasma. The study group consisted of 38 parturient women, 26 primiparous and 12 multiparous with normal course of pregnancy and delivery. The cord blood was sampled from the cord vein, and the mother's blood from the antecubital vein. 3.2% sodium citrate was used as an anticoagulant. TAFIa/ai antigen was measured by ELISA method. TAFIa/ai antigen was identified in all samples of cord blood plasma. Its level was 91.50 ng/ml (range: 71.76 - 160.77 ng/ml vs. 55.46 ng/ml (range: 39.77 - 68.54 ng/ml in the mother's blood, which means that the level of TAFIa/ai antigen was significantly higher in fetal blood than in maternal blood (p<0.00001. TAFIa/ai antigen is an integral component of cord blood plasma. The concentration of TAFIa/ai antigen is about two times higher in fetal blood than in maternal blood.

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.

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

International Nuclear Information System (INIS)

Miyata, Satoru; Toyoshima, Masanori; Otsuki, Yuzo; Nagata, Hiroshi; Nakamura, Shigenobu

1981-01-01

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 56 Mn derived from the 56 Fe(n, p) 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. (author)

Cord lactate, pH, and blood gases from healthy neonates.

Science.gov (United States)

Shirey, T; St Pierre, J; Winkelman, J

1996-01-01

Lactate, pH, pO2, and pCO2 were determined in arterial, venous, and free-flowing mixed umbilical cord blood obtained from deliveries of apparently healthy neonates. The goals of this study were to establish reference ranges for lactate and pH against which results in cases of high-risk labor and delivery could be compared, to see how the gases correlated with these values, and to determine whether easily accessible mixed umbilical cord blood can serve as the sample in lieu of cord arterial or cord venous blood. Arterial and venous cord lactates were 2.98 mmol/l (+/- 1.40) and 2.80 mmol/l (+/- 1.35), respectively, from 85 cords obtained from vaginal and cesarean deliveries. Mixed cord blood lactate, obtained on 48 cords, was 2.72 mmol/l (+/- 1.28) versus 3.14 and 2.97 mmol/l for the arterial and venous samples from those cords, respectively, and correlated quite well with lactate from the venous specimens (r = 0.97). Differences of > 0.5 mmol/l occurred between mixed and arterial cord bloods in 21 patients, and between mixed and venous cord bloods in 6 of the 48 patients, respectively. We conclude that (1) less than 2.5% of deliveries of apparently healthy neonates have arterial, venous, or mixed cord lactates > or = 7.0 mmol/l and pH pO2 nor pCO2 correlate well with cord venous lactate, and (3) readily available mixed cord blood is a satisfactory specimen for the measurement of venous cord latate.

Cord-Blood Banking

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... cord blood mainly because of the promise that stem cell research holds for the future. Most of us would have little use for stem cells now, but research into using them to treat diseases is ongoing — ...

Cure of beta-thalassaemia major by umbilical cord blood transplantation--a case report of Malaysia's first cord blood transplantation.

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Chan, L L; Lin, H P

1999-08-01

A 25-month-old boy with beta-thalassaemia major was presented with an opportunity for umbilical cord blood transplantation when his unborn sibling was diagnosed in utero to be a beta-thalassaemia carrier and also human leucocyte antigen compatible. A barely adequate amount of cord blood was collected at the birth of his sibling and infused into the patient after appropriate chemo-conditioning. Engraftment occurred without major complications. The subject is now alive and well 9 months post-transplant, thus marking our first success in umbilical cord blood transplantation.

Real-time direct measurement of spinal cord blood flow at the site of compression: relationship between blood flow recovery and motor deficiency in spinal cord injury.

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Hamamoto, Yuichiro; Ogata, Tadanori; Morino, Tadao; Hino, Masayuki; Yamamoto, Haruyasu

2007-08-15

An in vivo study to measure rat spinal cord blood flow in real-time at the site of compression using a newly developed device. To evaluate the change in thoracic spinal cord blood flow by compression force and to clarify the association between blood flow recovery and motor deficiency after a spinal cord compression injury. Until now, no real-time measurement of spinal cord blood flow at the site of compression has been conducted. In addition, it has not been clearly determined whether blood flow recovery is related to motor function after a spinal cord injury. Our blood flow measurement system was a combination of a noncontact type laser Doppler system and a spinal cord compression device. The rat thoracic spinal cord was exposed at the 11th vertebra and spinal cord blood flow at the site of compression was continuously measured before, during, and after the compression. The functioning of the animal's hind-limbs was evaluated by the Basso, Beattie and Bresnahan scoring scale and the frequency of voluntary standing. Histologic changes such as permeability of blood-spinal cord barrier, microglia proliferation, and apoptotic cell death were examined in compressed spinal cord tissue. The spinal blood flow decreased on each increase in the compression force. After applying a 5-g weight, the blood flow decreased to compression), while no significant difference was observed between the 20-minute ischemia group and the sham group. In the 20-minute ischemia group, the rats whose spinal cord blood flow recovery was incomplete showed significant motor function loss compared with rats that completely recovered blood flow. Extensive breakdown of blood-spinal cord barrier integrity and the following microglia proliferation and apoptotic cell death were detected in the 40-minute complete ischemia group. Duration of ischemia/compression and blood flow recovery of the spinal cord are important factors in the recovery of motor function after a spinal cord injury.

The biocompatibility of titanium cardiovascular devices seeded with autologous blood-derived endothelial progenitor cells: EPC-seeded antithrombotic Ti implants.

Science.gov (United States)

Achneck, Hardean E; Jamiolkowski, Ryan M; Jantzen, Alexandra E; Haseltine, Justin M; Lane, Whitney O; Huang, Jessica K; Galinat, Lauren J; Serpe, Michael J; Lin, Fu-Hsiung; Li, Madison; Parikh, Amar; Ma, Liqiao; Chen, Tao; Sileshi, Bantayehu; Milano, Carmelo A; Wallace, Charles S; Stabler, Thomas V; Allen, Jason D; Truskey, George A; Lawson, Jeffrey H

2011-01-01

Implantable and extracorporeal cardiovascular devices are commonly made from titanium (Ti) (e.g. Ti-coated Nitinol stents and mechanical circulatory assist devices). Endothelializing the blood-contacting Ti surfaces of these devices would provide them with an antithrombogenic coating that mimics the native lining of blood vessels and the heart. We evaluated the viability and adherence of peripheral blood-derived porcine endothelial progenitor cells (EPCs), seeded onto thin Ti layers on glass slides under static conditions and after exposure to fluid shear stresses. EPCs attached and grew to confluence on Ti in serum-free medium, without preadsorption of proteins. After attachment to Ti for 15 min, less than 5% of the cells detached at a shear stress of 100 dyne / cm(2). Confluent monolayers of EPCs on smooth Ti surfaces (Rq of 10 nm), exposed to 15 or 100 dyne/cm(2) for 48 h, aligned and elongated in the direction of flow and produced nitric oxide dependent on the level of shear stress. EPC-coated Ti surfaces had dramatically reduced platelet adhesion when compared to uncoated Ti surfaces. These results indicate that peripheral blood-derived EPCs adhere and function normally on Ti surfaces. Therefore EPCs may be used to seed cardiovascular devices prior to implantation to ameliorate platelet activation and thrombus formation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Umbilical cord blood banking ethico-legal issues: review article ...

African Journals Online (AJOL)

The recent discovery that umbilical cord blood has a high concentration of haematopoeitic stem cells has led to cord blood being used to treat a variety of disorders. Collection of cord blood is easy, non-invasive and generally does not interfere with the delivery process. However, there are various ethical and logistical ...

Human neural progenitors derived from integration-free iPSCs for SCI therapy

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Ying Liu

2017-03-01

Full Text Available As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs provide great capability for tissue regeneration, particularly in spinal cord injury (SCI. However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

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.

Barriers and motivators to blood and cord blood donations in young African-American women.

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Grossman, Brenda; Watkins, Andre R; Fleming, Faye; Debaun, Michael R

2005-03-01

The primary aim of this study was to assess potential barriers and motivators to blood and cord blood donation among African-American women. A telephone survey of African-American women, ages 18-30 years, in the St. Louis metropolitan area was performed. The survey was administered by trained telemarketing personnel using a Computer-Assisted Direct Interview (CADI) system. One hundred sixty-two women were surveyed. Common barriers to blood donation were inconvenience of donor sites (19%), fear of needles (16%), and too much time required to donate (15%). Potential motivators were increasing awareness of need for blood (43%), increasing the number of convenient donor locations (19%), and encouragement by spiritual leaders to have blood drives at their church (17%). Lack of awareness was the only identified barrier to cord blood donation. Most women surveyed (88%) indicated that they definitely or probably would donate cord blood. Strategies to increase the proportion of African-American blood and cord blood donations may include educating potential donors about the process and benefits of donation to particular patient populations and engaging church leadership in supporting blood and cord blood donations.

Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

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P. Alvarez

2013-01-01

Full Text Available Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a the role of different factors, such as stromal cell derived factor-1 (SDF-1, granulocyte colony-stimulating factor (G-CSF, and vascular cell adhesion molecule-1 (VCAM-1, among other ligands; (b the stem cell count in peripheral blood and BM and influential factors; (c the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

Stem cells of umbilical blood cord – therapeutic use

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Beata Bielec

2015-07-01

Full Text Available For many years, the transplantation of hematopoietic stem cells has been used to treat some diseases of the hematopoietic system. For a very long time, only bone marrow was used as a source of hematopoietic stem cells for this method of treatment. However, to comply with allogeneic bone marrow transplantation, an antigenically compatible donor is necessary. Transplantations from unrelated donors are associated with increased risk of a graft-versus-host reaction, transplant rejection and, consequently, increased mortality. Many years ago, it was found that umbilical cord blood as well as bone marrow and peripheral blood contains hematopoietic stem cells and mesenchymal cells able to differentiate into different cell types and that the umbilical cord blood can be a source of stem cells for transplantation. Following this discovery, numerous attempts were made for its potential use in the treatment of hematologic diseases, metabolic diseases as well as regenerative medicine. Umbilical cord blood stem cells exhibit intermediate characteristics between embryonic and adult stem cells. They are distinguished from the latter by telomere length, telomerase activity, and lower risk of accumulation of DNA mutations or chromosomal aberrations. The only transplantation limitation appears to be the amount of cord blood collected, which on average is sufficient for transplantation in a 40-50 kg child. Collection of cord blood is a simple, short-lasting treatment, not causing any danger for a newborn or the mother. Umbilical cord blood is obtained during labor, and then frozen and stored at cord blood banks all over the world.

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

-induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m......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...... stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment...

Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

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Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

2015-12-01

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

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...... of less than 0.5 IU/ml, although sensitivity to anti-IgE was universally increased. Preincubation with pharmacologic agents modulating the IgE-mediated HR produced effects generally similar to previous findings in adult blood. However, the effects of inhibiting the cyclooxygenase pathway in cord blood...

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.

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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

Arrest—Individual Treatment with Cord Blood

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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.

Transplantation of umbilical cord blood-derived cells for novel indications in regenerative therapy or immune modulation: a scoping review of clinical studies.

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Iafolla, Marco A J; Tay, Jason; Allan, David S

2014-01-01

Although used mainly for transplantation of hematopoietic stem cells in the treatment of blood disorders, umbilical cord blood (UCB)-based therapies are now being used increasingly for novel applications in nonhematopoietic diseases and as a form of cellular regenerative therapy or immune modulation. We performed a systematic scoping review by searching Medline, EMBASE, and the Cochrane Library for published articles, and we searched www.clinicaltrials.com and the World Health Organization International Clinical Trials Registry Platform to describe the breadth of published studies and ongoing clinical activity in umbilical cord-based cellular therapy for regenerative therapy and immune modulation. The most commonly published area of expertise in the use of UCB-derived cellular transplantation for novel indications is for neurological disorders and this remains the most active area of study in ongoing registered trials. An increasingly broad range of disorders, however, are reflected in ongoing registered trials, which suggests greater activity, interest, and investment in UCB-derived cellular therapy. Interestingly, adult patients compose the majority of patients reported in published reports and registered ongoing clinical studies continue to enroll predominantly adult subjects. Geographically, Asian countries appear most active in UCB-derived cellular therapy and our analysis of ongoing studies suggests this trend will likely continue. Regular assessment of published and ongoing activity in UCB transplantation for emerging novel indications will be critical for informing UCB banking establishments and funding agencies to guide changes in banking practices related to emerging trends in cell therapy. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England.

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Busby, Helen

2010-03-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public 'cord blood bank', for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed.

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

Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome

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Alexander E. Berezin

2016-09-01

Full Text Available Metabolic syndrome (MetS is defined as cluster of multiple metabolic and cardiovascular (CV abnormalities included abdominal obesity, high-normal blood pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has a growing prevalence worldwide. We investigated whether an elevated level of osteoprotegerin (OPG predicts imbalance between different phenotypes of circulating endothelial (EPCs and mononuclear (MPCs progenitor cells in MetS patients. We have analyzed data regarding dysmetabolic disorder subjects without known CV disease, as well as with known type two diabetes mellitus. All patients have given their informed written consent for participation in the study. This article contains data on the independent predictors of depletion in numerous of circulating EPCs and MPCs in MetS patients. The data are supplemental to our original research article describing detailed associations of elevated OPG level in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk factors. Keywords: Metabolic syndrome, Osteoprotegerin, Circulating endothelial derived progenitor cells, Mononuclear-derived progenitor cells

Differentiation stage-specific regulation of primitive human hematopoietic progenitor cycling by exogenous and endogenous inhibitors in an in vivo model.

Science.gov (United States)

Cashman, J D; Clark-Lewis, I; Eaves, A C; Eaves, C J

1999-12-01

Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice transplanted with human cord blood or adult marrow cells and injected 6 weeks posttransplant with 2 daily doses of transforming growth factor-beta(1) (TGF-beta(1)), monocyte chemoattractant protein-1 (MCP-1), or a nonaggregating form of macrophage inflammatory protein-1alpha (MIP-1alpha) showed unique patterns of inhibition of human progenitor proliferation 1 day later. TGF-beta(1) was active on long-term culture initiating cells (LTC-IC) and on primitive erythroid and granulopoietic colony-forming cells (HPP-CFC), but had no effect on mature CFC. MCP-1 inhibited the cycling of both types of HPP-CFC but not LTC-IC. MIP-1alpha did not inhibit either LTC-IC or granulopoietic HPP-CFC but was active on erythroid HPP-CFC and mature granulopoietic CFC. All of these responses were independent of the source of human cells transplanted. LTC-IC of either human cord blood or adult marrow origin continue to proliferate in NOD/SCID mice for many weeks, although the turnover of all types of human CFC in mice transplanted with adult human marrow (but not cord blood) is downregulated after 6 weeks. Interestingly, administration of either MIP-1beta, an antagonist of both MIP-1alpha and MCP-1 or MCP-1(9-76), an antagonist of MCP-1 (and MCP-2 and MCP-3), into mice in which human marrow-derived CFC had become quiescent, caused the rapid reactivation of these progenitors in vivo. These results provide the first definition of stage-specific inhibitors of human hematopoietic progenitor cell cycling in vivo. In addition they show that endogenous chemokines can contribute to late graft failure, which can be reversed by the administration of specific antagonists.

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England

OpenAIRE

Busby, Helen

2010-01-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public ‘cord blood bank’, for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with ...

Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

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Margie eCastillo-Melendez

2013-10-01

Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

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...... treatment and susceptibility to infections. We conclude that SP-D concentrations in umbilical cord blood and capillary blood in premature infants are twice as high as in mature infants and depend on several perinatal conditions. High SP-D levels in umbilical cord blood and capillary blood on day 1 were...... found to be related to increased risk of RDS and infections....

Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

Science.gov (United States)

Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

2015-03-01

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells on the radiation-induced GI syndrome

Energy Technology Data Exchange (ETDEWEB)

Shim, Se Hwan; Jang, Won Suk; Lee, Sun Joo; Park, Eun Young; Kim, Youn Joo; Jin, Sung Ho; Park, Sun Hoo; Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2011-05-15

The gastrointestinal (GI) tract is one of the most radiosensitive organ systems in the body. Radiation-induced GI injury is described as destruction of crypt cell, decrease in villous height and number, ulceration, and necrosis of intestinal epithelium. Studies show that mesenchymal stem cells (MSCs) treatment may be useful in the repair or regeneration of damaged organs including bone, cartilage, or myocardium. MSCs from umbilical cord blood (UCB) have many advantages because of the immature nature of newborn cells compared to bone marrow derived MSCs. Moreover, UCB-MSCs provide no ethical barriers for basic studies and clinical applications. In this study, we explore the regeneration capability of human UCB-MSCs after radiation-induced GI injury

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.

Can routine commercial cord blood banking be scientifically and ethically justified?

Directory of Open Access Journals (Sweden)

Nicholas M Fisk

2005-02-01

Full Text Available BACKGROUND TO THE DEBATE: Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation.

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.

Motivating Cord Blood Donation with Information and Behavioral Nudges.

Science.gov (United States)

Grieco, Daniela; Lacetera, Nicola; Macis, Mario; Di Martino, Daniela

2018-01-10

Umbilical cord blood is a source of hematopoietic stem cells essential to treat life-threatening diseases, such as leukemia and lymphoma. However, only a very small percentage of parents donate upon delivery. The decision to donate the cord blood occurs at a very specific time and when parents likely experience emotional, informational, and decisional overloads; these features of cord blood donation make it different from other pro-social activities. In collaboration with an OB-GYN clinic in Milan, Italy, we conducted the first randomized controlled trial that applies tools from behavioral science to foster cord blood donation, and quantified the gains that informational and behavioral "nudges" can achieve. We found that information and "soft" commitments increased donations; approaching expecting parents closer to the delivery date and providing them with multiple reminders, moreover, had the strongest impact. However, a significant portion of women who expressed consent to donate could not do so because of organizational constraints. We conclude that simple, non-invasive behavioral interventions that address information gaps and procrastination, and that increase the salience of the activity can substantially enhance altruistic donations of cord blood, especially when coupled with organizational support.

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....... Results The proliferative response of cord blood (CB)-derived mononuclear cells towards allergen-preparations at day 3 was related to the level of LPS contamination. At day 7, proliferation was also detected in the absence of endotoxin. Cytokine production in CB was strongly affected by the content...

Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review.

Science.gov (United States)

Mazensky, David; Flesarova, Slavka; Sulla, Igor

2017-12-01

Animal models are used to examine the results of experimental spinal cord injury. Alterations in spinal cord blood supply caused by complex spinal cord injuries contribute significantly to the diversity and severity of the spinal cord damage, particularly ischemic changes. However, the literature has not completely clarified our knowledge of anatomy of the complex three-dimensional arterial system of the spinal cord in experimental animals, which can impede the translation of experimental results to human clinical applications. As the literary sources dealing with the spinal cord arterial blood supply in experimental animals are limited and scattered, the authors performed a review of the anatomy of the arterial blood supply to the spinal cord in several experimental animals, including pigs, dogs, cats, rabbits, guinea pigs, rats, and mice and created a coherent format discussing the interspecies differences. This provides researchers with a valuable tool for the selection of the most suitable animal model for their experiments in the study of spinal cord ischemia and provides clinicians with a basis for the appropriate translation of research work to their clinical applications. Anat Rec, 300:2091-2106, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin.

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Kim, Yoon-Jin; Yoo, Sae Mi; Park, Hwan Hee; Lim, Hye Jin; Kim, Yu-Lee; Lee, Seunghee; Seo, Kwang-Won; Kang, Kyung-Sun

2017-11-18

Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) play an important role in cutaneous wound healing, and recent studies suggested that MSC-derived exosomes activate several signaling pathways, which are conducive in wound healing and cell growth. In this study, we investigated the roles of exosomes that are derived from USC-CM (USC-CM Exos) in cutaneous collagen synthesis and permeation. We found that USC-CM has various growth factors associated with skin rejuvenation. Our in vitro results showed that USC-CM Exos integrate in Human Dermal Fibroblasts (HDFs) and consequently promote cell migration and collagen synthesis of HDFs. Moreover, we evaluated skin permeation of USC-CM Exos by using human skin tissues. Results showed that Exo-Green labeled USC-CM Exos approached the outermost layer of the epidermis after 3 h and gradually approached the epidermis after 18 h. Moreover, increased expressions of Collagen I and Elastin were found after 3 days of treatment on human skin. The results showed that USC-CM Exos is absorbed into human skin, it promotes Collagen I and Elastin synthesis in the skin, which are essential to skin rejuvenation and shows the potential of USC-CM integration with the cosmetics or therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Science.gov (United States)

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Neuroblast survival depends on mature vascular network formation after mouse stroke: role of endothelial and smooth muscle progenitor cell co-administration.

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Nih, Lina R; Deroide, Nicolas; Leré-Déan, Carole; Lerouet, Dominique; Soustrat, Mathieu; Levy, Bernard I; Silvestre, Jean-Sébastien; Merkulova-Rainon, Tatiana; Pocard, Marc; Margaill, Isabelle; Kubis, Nathalie

2012-04-01

Pro-angiogenic cell-based therapies constitute an interesting and attractive approach to enhancing post-stroke neurogenesis and decreasing neurological deficit. However, most new stroke-induced neurons die during the first few weeks after ischemia, thus impairing total recovery. Although the neovascularization process involves different cell types and various growth factors, most cell therapy protocols are based on the biological effects of single-cell-type populations or on the administration of heterogeneous populations of progenitors, namely human cord blood-derived CD34(+) cells, with scarce vascular progenitor cells. Tight cooperation between endothelial cells and smooth muscle cells/pericytes is critical for the development of functional neovessels. We hypothesized that neuroblast survival in stroke brain depends on mature vascular network formation. In this study, we injected a combination of endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs), isolated from human umbilical cord blood, into a murine model of permanent focal ischemia induced by middle cerebral artery occlusion. The co-administration of SMPCs and EPCs induced enhanced angiogenesis and vascular remodeling in the peri-infarct and infarct areas, where vessels exhibited a more mature phenotype. This activation of vessel growth resulted in the maintenance of neurogenesis and neuroblast migration to the peri-ischemic cortex. Our data suggest that a mature vascular network is essential for neuroblast survival after cerebral ischemia, and that co-administration of EPCs and SMPCs may constitute a novel therapeutic strategy for improving the treatment of stroke. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Complete blood count reference values of cord blood in Taiwan and the influence of gender and delivery route on them.

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Chang, Yu-Hsun; Yang, Shang-Hsien; Wang, Tso-Fu; Lin, Teng-Yi; Yang, Kuo-Liang; Chen, Shu-Huey

2011-06-01

Cord blood banking has become more popular in recent years. Checking cord blood complete blood count (CBC) and white blood cell (WBC) differential counts (DCs) is essential before cryopreserving the cord blood units. Therefore, establishing the normal reference values of cord blood CBC and WBC DC is important in clinical practice and research. To obtain a large-scale population-based normal CBC and WBC DC reference values of healthy neonates' cord blood from a public cord blood bank and to investigate the influence of the gender and delivery route. From September 2001 to November 2006, the cord blood of healthy Taiwanese neonates with gestational age 36 weeks and more were collected by Tzu Chi Cord Blood Bank with written informed consents. All cord blood samples were analyzed by Sysmex XE2100 automated hematology analyzer (Sysmex Corporation, Kobe, Japan) to obtain the CBC. The WBC DC was calculated by manual method. We used Student's t test and Mann-Whitney U test for investigating the influences of gender and delivery route on the CBC and WBC DC reference values. The results were presented by mean±standard deviation or 2.5-97.5th percentiles. In the study period, totally 5602 cord blood samples were collected eligibly for analysis. The cord blood CBC and WBC DC normal reference values were calculated. The female neonates had significantly higher mean corpuscular volume, platelet count, and WBC count, but lower red blood cell (RBC) count, hemoglobin (Hb), hematocrit, and mean corpuscular Hb concentration values (pTaiwan. Gender and delivery routes were important confounding factors that influenced the cord blood CBC and WBC DC values. Copyright © 2011. Published by Elsevier B.V.

Chronic Myeloid Leukemia Blood Inflicted Injury in Cord Derived Wharton's Jelly Mesenchymal Stem Cells

International Nuclear Information System (INIS)

Wajid, N.; Ali, M.; Javed, S.; Ali, F.; Anwar, S. S.

2016-01-01

Objective: To determine the effects of blood from CML patients on human umbilical cord derived Wharton's jelly mesenchymal stem cells (WJMSCs) for evaluation of their therapeutic potential. Study Design: An experimental study. Place and Duration of Study: Centre for Research in Molecular Medicine, University of Lahore, from September 2013 to December 2014. Methodology: Possible behavior of WJMSCs in CML patients was assessed by culturing these cells in their plasma. WJMSCs at passage 3 were cultured in plasma isolated from 9 CML patients as well as 9 normal subjects. Effects on cell viability, proliferation, LDH release, paracrine factors (p38 and p53) and oxidative stress were evaluated. Result: WJMSCs cultured in plasma of CML patients showed decreased viability, slow proliferation, high LDH release, high expression of p38 and p53 and a high oxidative stress compared to normal subjects. Conclusion: Stressed environment of CML patients' blood/plasma induced injury to WJMSCs as well as reduced their viability. Effectiveness of these cells for therapeutics of CML is, therefore, likely to be reduced. (author)

ACOG committee opinion number 399, February 2008: umbilical cord blood banking.

Science.gov (United States)

2008-02-01

Two types of banks have emerged for the collection and storage of umbilical cord blood--public banks and private banks. Public banks promote allogenic (related or unrelated) donation, analogous to the current collection of whole blood units in the United States. Private banks were initially developed to store stem cells from umbilical cord blood for autologous use (taken from an individual for subsequent use by the same individual) by a child if the child develops disease later in life. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public versus private banking should be provided. The remote chance of an autologous unit of umbilical cord blood being used for a child or a family member (approximately 1 in 2,700 individuals) should be disclosed. The collection should not alter routine practice for the timing of umbilical cord clamping. Physicians or other professionals who recruit pregnant women and their families for for-profit umbilical cord blood banking should disclose any financial interests or other potential conflicts of interest.

Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.

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Shechter, Ravid; London, Anat; Varol, Chen; Raposo, Catarina; Cusimano, Melania; Yovel, Gili; Rolls, Asya; Mack, Matthias; Pluchino, Stefano; Martino, Gianvito; Jung, Steffen; Schwartz, Michal

2009-07-01

Although macrophages (MPhi) are known as essential players in wound healing, their contribution to recovery from spinal cord injury (SCI) is a subject of debate. The difficulties in distinguishing between different MPhi subpopulations at the lesion site have further contributed to the controversy and led to the common view of MPhi as functionally homogenous. Given the massive accumulation in the injured spinal cord of activated resident microglia, which are the native immune occupants of the central nervous system (CNS), the recruitment of additional infiltrating monocytes from the peripheral blood seems puzzling. A key question that remains is whether the infiltrating monocyte-derived MPhi contribute to repair, or represent an unavoidable detrimental response. The hypothesis of the current study is that a specific population of infiltrating monocyte-derived MPhi is functionally distinct from the inflammatory resident microglia and is essential for recovery from SCI. We inflicted SCI in adult mice, and tested the effect of infiltrating monocyte-derived MPhi on the recovery process. Adoptive transfer experiments and bone marrow chimeras were used to functionally distinguish between the resident microglia and the infiltrating monocyte-derived MPhi. We followed the infiltration of the monocyte-derived MPhi to the injured site and characterized their spatial distribution and phenotype. Increasing the naïve monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Selective ablation of infiltrating monocyte-derived MPhi following SCI while sparing the resident microglia, using either antibody-mediated depletion or conditional ablation by diphtheria toxin, impaired recovery. Reconstitution of the peripheral blood with monocytes resistant to ablation restored the lost motor functions. Importantly, the infiltrating monocyte-derived MPhi displayed a local anti

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

African Journals Online (AJOL)

Uche

Background: Umbilical cord blood analysis may give a clue to the state of health of both pregnant mothers and their neonates. However ... Keywords: Umbilical cord blood; maternal blood; haemoglobin concentration; packed cell volume; red cell indices. Received on .... The packed cell volume was measured using the.

Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia

International Nuclear Information System (INIS)

Wisniewski, D; Affer, M; Willshire, J; Clarkson, B

2011-01-01

The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin−CD34+CD38−CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin−CD34+CD38−CD90+CD45RA− HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin−CD34+CD38−CD90+CD45RA− sub-population

ASSOCIATION OF BIRTH ASPHYXIA WITH CORD BLOOD NUCLEATED RED BLOOD CELL

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Poornima Shankar

2018-02-01

Full Text Available BACKGROUND Asphyxia can lead to severe hypoxic ischaemic organ damage in new-borns which may cause postnatal manifestation of hypoxicischaemic encephalopathy. Studies have found that the Apgar score failed to predict specific neurologic outcomes of the infants. Increased cord blood nucleated red blood cell in term neonates is an indicator of chronic intrauterine hypoxia. We set out to assess the role of nucleated RBC as a non-invasive, easy, cheap and at the same time early biochemical means of asphyxia diagnosis in our clinical setting. MATERIALS AND METHODS All inborn babies with Apgar scores <7 at 1 and 5 minutes of life were reviewed. Relevant information from mother case sheet were obtained. Cord blood samples was drawn and sent for blood gas analysis and number of NRBCs/100 white blood cells (WBC was determined using Leishman stain. RESULTS Our study proves the relevance of increase nucleated RBC in terms of early detection of birth asphyxia. Most common cause of birth asphyxia found was meconium aspiration. No co-relation was found with chorioamnionitis or maternal obstetrical history. CONCLUSION Many specific biomarkers are being investigated now a day for early detection of birth asphyxia. Umbilical cord pH is costly and may be underestimated in birth asphyxia. In our study, the elevated cord blood nRBC count was shown to be a good predictor of perinatal asphyxia. Since, it is cost-effective and does not require any special expertise or any high-tech facilities, it may be a useful, reliable, inexpensive and easily available marker to evaluate perinatal asphyxia. Hence, increase nucleated RBC has an important role in diagnosing and predicting the outcome of perinatal asphyxia.

Isolation and characterization of human umbilical cord-derived endothelial colony-forming cells

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Zhang, Hao; Tao, Yanling; Ren, Saisai; Liu, Haihui; Zhou, Hui; Hu, Jiangwei; Tang, Yongyong; Zhang, Bin; Chen, Hu

2017-01-01

Endothelial colony-forming cells (ECFCs) are a population of endothelial progenitor cells (EPCs) that display robust proliferative potential and vessel-forming capability. Previous studies have demonstrated that a limited number of ECFCs may be obtained from adult bone marrow, peripheral blood and umbilical cord (UC) blood. The present study describes an effective method for isolating ECFCs from human UC. The ECFCs derived from human UC displayed the full properties of EPCs. Analysis of the growth kinetics, cell cycle and colony-forming ability of the isolated human UC-ECFCs indicated that the cells demonstrated properties of stem cells, including relative stability and rapid proliferation in vitro. Gene expression of Fms related tyrosine kinase 1, kinase insert domain receptor, vascular endothelial cadherin, cluster of differentiation (CD)31, CD34, epidermal growth factor homology domains-2, von Willebrand factor and endothelial nitric oxide synthase was assessed by reverse transcription-polymerase chain reaction. The cells were positive for CD34, CD31, CD73, CD105 and vascular endothelial growth factor receptor-2, and negative for CD45, CD90 and human leukocyte antigen-antigen D related protein according to flow cytometry. 1,1′-dioctadecyl-3,3,3′,3′-tetra-methyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein and fluorescein isothiocyanate-Ulex europaeus-l were used to verify the identity of the UC-ECFCs. Matrigel was used to investigate tube formation capability. The results demonstrated that the reported technique is a valuable method for isolating human UC-ECFCs, which have potential for use in vascular regeneration. PMID:29067104

Thyroid Stimulating Hormone values from cord blood in neonates ...

African Journals Online (AJOL)

Objectives: To determine thyroid stimulating hormone (TSH) levels from cord blood in neonates and to establish the practice for possible application of congenital hypothyroidism screening in Ethiopia. Methods: TSH was measured from cord blood of 1207 consecutive new-borns in the maternal wards of St. Paul, Ghandi ...

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

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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.

Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development

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M.T. Abd El Aziz

2015-03-01

Full Text Available We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs, examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI. EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1. EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

A new strategy for umbilical cord blood collection developed at the first Colombian public cord blood bank increases total nucleated cell content.

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Vanegas, Diana; Triviño, Lady; Galindo, Cristian; Franco, Leidy; Salguero, Gustavo; Camacho, Bernardo; Perdomo-Arciniegas, Ana-María

2017-09-01

The total nucleated cell dosage of umbilical cord blood (UCB) is an important factor in determining successful allogeneic hematopoietic stem cell transplantation after a minimum human leukocyte antigen donor-recipient match. The northern South American population is in need of a new-generation cord blood bank that cryopreserves only units with high total nucleated cell content, thereby increasing the likelihood of use. Colombia set up a public cord blood bank in 2014; and, as a result of its research for improving high total nucleated cell content, a new strategy for UCB collection was developed. Data from 2933 collected and 759 cryopreserved cord blood units between 2014 and 2015 were analyzed. The correlation of donor and collection variables with cellularity was evaluated. Moreover, blood volume, cell content, CD34+ count, clonogenic capacity, and microbial contamination were assessed comparing the new method, which combines in utero and ex utero techniques, with the conventional strategies. Multivariate analysis confirmed a correlation between neonatal birth weight and cell content. The new collection method increased total nucleated cell content in approximately 26% and did not alter pre-cryopreservation and post-thaw cell recovery, viability, or clonogenic ability. Furthermore, it showed a remarkably low microbial contamination rate (1.2%). The strategy for UCB collection developed at the first Colombian public cord blood bank increases total nucleated cell content and does not affect unit quality. The existence of this bank is a remarkable breakthrough for Latin-American patients in need of this kind of transplantation. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

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

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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).

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

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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

Freeze-drying of mononuclear cells derived from umbilical cord blood followed by colony formation.

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Dity Natan

Full Text Available BACKGROUND: We recently showed that freeze-dried cells stored for 3 years at room temperature can direct embryonic development following cloning. However, viability, as evaluated by membrane integrity of the cells after freeze-drying, was very low; and it was mainly the DNA integrity that was preserved. In the present study, we improved the cells' viability and functionality after freeze-drying. METHODOLOGY/PRINCIPAL FINDINGS: We optimized the conditions of directional freezing, i.e. interface velocity and cell concentration, and we added the antioxidant EGCG to the freezing solution. The study was performed on mononuclear cells (MNCs derived from human umbilical cord blood. After freeze-drying, we tested the viability, number of CD34(+-presenting cells and ability of the rehydrated hematopoietic stem cells to differentiate into different blood cells in culture. The viability of the MNCs after freeze-drying and rehydration with pure water was 88%-91%. The total number of CD34(+-presenting cells and the number of colonies did not change significantly when evaluated before freezing, after freeze-thawing, and after freeze-drying (5.4 x 10(4+/-4.7, 3.49 x 10(4+/-6 and 6.31 x 10(4+/-12.27 cells, respectively, and 31+/-25.15, 47+/-45.8 and 23.44+/-13.3 colonies, respectively. CONCLUSIONS: This is the first report of nucleated cells which have been dried and then rehydrated with double-distilled water remaining viable, and of hematopoietic stem cells retaining their ability to differentiate into different blood cells.

Evaluation of Peripheral Blood and Cord Blood Platelet Lysates in Isolation and Expansion of Multipotent Mesenchymal Stromal Cells

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Ioanna Christou

2018-02-01

Full Text Available Background: Multipotent Mesenchymal Stromal Cells (MSCs are used in tissue engineering and regenerative medicine. The in vitro isolation and expansion of MSCs involve the use of foetal bovine serum (FBS. However, many concerns have been raised regarding the safety of this product. In this study, alternative additives derived either from peripheral or cord blood were tested as an FBS replacement. Methods: Platelet lysates (PL from peripheral and cord blood were used for the expansion of MSCs. The levels of growth factors in peripheral blood (PB and cord blood (CB PLs were determined using the Multiple Reaction Monitoring (MRM. Finally, the cell doubling time (CDT, tri-lineage differentiation and phenotypic characterization of the MSCs expanded with FBS and PLs were determined. Results: MSCs treated with culture media containing FBS and PB-PL, were successfully isolated and expanded, whereas MSCs treated with CB-PL could not be maintained in culture. Furthermore, the MRM analysis yielded differences in growth factor levels between PB-PL and CB-PL. In addition, the MSCs were successfully expanded with FBS and PB-PL and exhibited tri-lineage differentiation and stable phenotypic characteristics. Conclusion: PB-PL could be used as an alternative additive for the production of MSCs culture medium applied to xenogeneic-free expansion and maintenance of MSCs in large scale clinical studies.

Concepts, Utility and Limitations of Cord Blood Banking: What Clinicians Need to Know.

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Narayanan, Dhanya Lakshmi; Phadke, Shubha R

2018-03-20

Stem cell transplantation and cord blood banking have received much popularity among general public and medical professionals in the recent past. But information about the scientific aspects, its utility and limitations is incomplete amongst laypersons as well as many medical practitioners. Stem cells differ from all other types of cells in the human body because of their ability to multiply in order to self perpetuate and differentiate into specialized cells. Stems cells could be totipotent, multipotent, pluripotent, oligopotent or unipotent depending on the type of cells that can arise or differentiate from them. Umbilical cord blood serves as a potent source of hematopoeitic stem cells and is being used to treat various disorders like blood cancers, hemoglobinopathies and immunodeficiency disorders for which hematological stem cell transplantation is the standard of care. Cord blood can be collected at ease, without any major complications and has a lower incidence of graft vs. host reaction compared to bone marrow cells or peripheral blood cells. Both public and private banks have been established for collection and storage of umbilical cord blood. However, false claims and misleading commercial advertisements about the use of umbilical cord blood stem cells for the treatment of a variety of conditions ranging from neuromuscular disorders to cosmetic benefits are widespread and create unrealistic expectations in laypersons and clinicians. Many clinicians and laypersons are unaware of the limitations of cord blood banking, as in treating a genetic disorder by autologous cord blood transplant. Knowledge and awareness about the scientific indications of cord blood stem cell transplantation and realistic expectations about the utility of cord blood among medical practitioners are essential for providing accurate information to laypersons before they decide to preserve umbilical cord blood in private banks and thus prevent malpractice.

Total and antigen-specific Ige levels in umbilical cord blood

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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

Optimization of informed consent for umbilical cord blood banking.

Science.gov (United States)

Sugarman, Jeremy; Kurtzberg, Joanne; Box, Tamara L; Horner, Ronnie D

2002-12-01

The purpose of this project was to evaluate the informed consent process for donation to a public umbilical cord blood bank. Telephone interviews were conducted with 170 women who had given consent to donate their newborn infants' umbilical cord blood. Of the 170 women who were contacted, 96.8% of the women reported that all their questions had been answered. Nevertheless, approximately one third of the respondents did not consider themselves to be in research, and almost one quarter of the respondents did not know how to contact the umbilical cord blood bank if they or their infant became seriously ill. Further, a substantial proportion of the respondents did not understand the full range of alternatives to donation and incorrectly endorsed potential benefits. Informed consent could be optimized by (1) having those personnel who obtain consent emphasize that banking involves research and to explain the true benefits of donation, (2) ensuring that parents know how and when to contact the umbilical cord blood bank after donation, and (3) using phone surveys to continue assessments and to monitor changes in the process.

A Study on the Correlation between Cord Blood Glucose Level and the Apgar Score.

Science.gov (United States)

Khan, Kalyan; Saha, Ashis Ranjan

2013-02-01

The study of the biochemical parameters of cord blood acts as a mirror, which usually reflects the neonatal status. The widely used system for the evaluation of a neonate is the Apgar score. There is no comprehensive published data which has established the association between the cord blood glucose level and the Apgar score. Similarly, there is also no well accepted reference range of the cord blood glucose level. The main objectives of the present study was to ascertain any adverse effects of an abnormal cord blood glucose level on the neonatal status and to find out a standard reference level of glucose in cord blood. The cord blood glucose estimation was done by using the glucose oxidase peroxidase method and the statistical analysis was performed by using the SPSS, version 16 software. In the present study, the cord blood glucose level was found to have no correlation with the Apgar scores which were calculated at both one minute and five minutes after birth. It was also found that for the foetus to be free from any obvious complication, the cord blood glucose level had to be around 87 mg/dl. The fluctuations in the maternal glucose levels are weakly associated with the glucose level in the cord blood.

Acceptance of Umbilical Cord Blood as an Alternative to Adult Blood ...

African Journals Online (AJOL)

Background: Inadequate supply of safe blood has been a source of worry to health facilities in Nigeria. One way of addressing this is problem is to consider the use of Umbilical Cord Blood (UCB) as an alternative to adult blood for the purpose of blood transfusion. This will only be possible if we accept this alternative.

One-unit versus two-unit cord-blood transplantation for hematologic cancers.

Science.gov (United States)

Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne

2014-10-30

Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the

Prediction of allergy from family history and cord blood IgE levels. A follow-up at the age of 5 years. Cord blood IgE. IV

DEFF Research Database (Denmark)

Hansen, L G; Halken, S; Høst, A

1993-01-01

was not influenced by cord blood IgE levels or atopic predisposition. Cord blood IgE levels had a low sensitivity as a predictor of atopic disease. A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found (p ... with elevated cord blood IgE levels developed allergic disease before 5 years of age (p 63 kU/l (geometric mean + 1 SD) at the age of 5 years can be regarded as being an elevated level. A cord...... blood IgE level > or = 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease, especially allergic bronchial asthma. With regard to allergic disease, the positive predictive value was 26%, the sensitivity 33% and the rate ratio for development of allergic 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 Birth...

Involvement of placental/umbilical cord blood acid-base status and gas values on the radiosensitivity of human fetal/neonatal hematopoietic stem/progenitor cells

International Nuclear Information System (INIS)

Yamaguchi, Masaru; Ebina, Satoko; Kashiwakura, Ikuo

2013-01-01

Arterial cord blood (CB) acid-base status and gas values, such as pH, PCO 2 , PO 2 , HCO 3 - and base excess, provide useful information on the fetal and neonatal condition. However, it remains unknown whether these values affect the radiosensitivity of fetal/neonatal hematopoiesis. The present study evaluated the relationship between arterial CB acid-base status, gas values, and the radiosensitivity of CB hematopoietic stem/progenitor cells (HSPCs). A total of 25 CB units were collected. The arterial CB acid-base status and gas values were measured within 30 min of delivery. The CD34 + HSPCs obtained from CB were exposed to 2 Gy X-irradiation, and then assayed for colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid (BFU-E), and colony-forming unit-granulocyte erythroid, macrophage and megakaryocyte cells. Acid-base status and gas values for PCO 2 and HCO 3 - showed a statistically significant negative correlation with the surviving fraction of BFU-E. In addition, a significant positive correlation was observed between gestational age and PCO 2 . Moreover, the surviving fraction of BFU-E showed a significant negative correlation with gestational age. Thus, HSPCs obtained from CB with high PCO 2 /HCO 3 - levels were sensitive to X-irradiation, which suggests that the status of arterial PCO 2 /HCO 3 - influences the radiosensitivity of fetal/neonatal hematopoiesis, especially erythropoiesis. (author)

Umbilical cord blood glucose levels in full-term newborns

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A. L. Karpova

2014-01-01

Full Text Available The purpose of the investigation was to determine the umbilical cord venous blood level of glucose in full-term newborns and its relationship to the mode of delivery. The investigation included 102 full-term newborn infants, including 33 and 69 babies born via cesar-ean and vaginal delivery, respectively. Umbilical cord serum glucose levels were determined by the glucose oxidase test using a Sap-phire-400 biochemical analyzer. In healthy full-term newborns, the mean umbilical cord blood glucose levels were 4,29±0,88 mmol/1 (minimum, 2,9 mmol/1 and maximum, 5,9 mmol/1. In the babies born via cesarean delivery, the umbilical cord blood concentration of glucose was ascertained to be significantly lower than in those born vaginally (3,84+0,71 mmol/1 versus 4,51+0,87 mmol/1; /><0,0001. Abdominal delivery can be apparently considered to be a risk factor for hypoglycemia in neonatal infants.

MR diffusion tensor imaging in the evaluation of neural progenitor cells transplantation to acute injured canine spinal cord

International Nuclear Information System (INIS)

Wang Xiaoying; Tan Ke; Ni Shilei; Bao Shengde; Jiang Xuexiang

2006-01-01

Objective: To observe the effect of transplantation of telomerase immortalized human neural progenitor cells to acute injured canine spinal cord by using MR diffusion tensor imaging (DTI). Methods: Telomerase immortalized human neural progenitor cells with expression of green fluorescent protein were prepared for transplantation. Eight adult canines with left spinal cord hemisection at the level of T13 were examined by MR diffusion tensor imaging four times sequentially: prior to injury, one week after injury, one week after transplantation (two weeks after injury), and four weeks after transplantation. Results: The ADC values of the injured spinal cord were (1.00 ± 0.15) x 10 -3 mm 2 /s, (1.65 ± 0.45) x 10 -3 mm 2 /s, (1.44 ± 0.48) xl0 -3 mm 2 /s, and (1.43 ± 0.26) x 10 -3 mm 2 /s, respectively. There was statistically significant difference between the data obtained at different times (F= 6.038, P=0.005). The FA values of the injured spinal cord were 0.59±0.11, 0.30±0.17, 0.36±0.25, and 0.34±0.11, respectively. There was also statistically significant difference between the data obtained at different times (F=5.221, P=0.009). The ADC values of the intact spinal cord were (1.01±0.17) x 10 -3 mm 2 /s, (1.32±0.06) x 10 -3 mm 2 /s, (1.10±0.24) x 10 -3 mm 2 /s, and (1.14±0.22) x 10 -3 mm 2 /s, respectively. There was no statistically significant difference between the data obtained at different times (F=1.303, P=0.306). The FA values of the intact spinal cord were 0.60 ± 0.09, 0.38 ± 0.25, 0.46 ± 0.15, and 0.50 ± 0.21, respectively. There was also no statistically significant difference between the data obtained at different times (F=2.797, P=0.072). Conclusion: DTI can provide useful information for spinal cord injury and regeneration in experimental spinal cord injury. (authors)

A Comparative Study to Evaluate Myogenic Differentiation Potential of Human Chorion versus Umbilical Cord Blood-derived Mesenchymal Stem Cells.

Science.gov (United States)

Bana, Nikoo; Sanooghi, Davood; Soleimani, Mansoureh; Hayati Roodbari, Nasim; Alavi Moghaddam, Sepideh; Joghataei, Mohammad Taghi; Sayahpour, Forough Azam; Faghihi, Faezeh

2017-08-01

Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine. To do that, neonate placenta Umbilical Cord Blood were transferred to the lab. After characterization of the isolated cells using flowcytometry and multilineage differentiation capacity, the obtained Mesenchymal Stem Cells were cultured in DMEM/F12 supplemented with 2% FBS and 10μM of 5-azacytidine to induce myogenic differentiation. Real-time PCR and immunocytochemistry were used to assess the myogenic properties of the cells. Our data showed that C-MSCs and UCB-MSCs were spindle shape in morphology. They were positive for CD90, CD73 and CD44 antigens, and negative for hematopoietic markers. They also differentiated into osteoblast and adipoblast lineages. Real-time PCR results showed that the cells could express MyoD, desmin and α-MHC at the end of the first week (P<0.05). No significant upregulation was detected in the expression of GATA-4 in both groups. Immunocytochemical staining revealed the expression of Desmin, cTnT and α-MHC. Results showed that these cells are potent to differentiate into myoblast- like cells. An upregulation in the expression of some myogenic markers (desmin, α- MHC) was observed in C-MSCs in comparison with UCB-MSCs. Copyright © 2017. Published by Elsevier Ltd.

US public cord blood banking practices: recruitment, donation, and the timing of consent.

Science.gov (United States)

Broder, Sherri M; Ponsaran, Roselle S; Goldenberg, Aaron J

2013-03-01

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. 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. Thirteen of 16 participants reported a variably high percentage of women who consented to public cord blood donation. Fifteen banks offered donor registration at the time of hospital admission for labor and delivery. Seven obtained full informed consent and medical history during early labor and eight conducted some form of phased consent and/or phased medical screening and history. Nine participants identified initial selection of the collection site location as the chief mode by which they recruited minority donors. 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. © 2012 American Association of Blood Banks.

T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

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Kim Tae-Sik

2011-06-01

Full Text Available Abstract Background Although the graft-versus-tumor (GVT effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

Excluding Anti-cytomegalovirus Immunoglobulin M-Positive Cord Blood Units Has a Minimal Impact on the Korean Public Cord Blood Bank Inventory.

Science.gov (United States)

Shin, Sue; Roh, Eun Youn; Oh, Sohee; Song, Eun Young; Kim, Eui Chong; Yoon, Jong Hyun

2017-01-24

Cord blood units (CBUs) for transplantation should be free of communicable disease and must contain a specific amount of total nucleated cells and CD34+ cells. Although posttransplantation cytomegalovirus (CMV) infections are from latent infection in patients, ensuring CMV-free CBUs by performing CMV-specific IgM and nucleic acid amplification testing (NAT) is one of the mandatory procedures for the safety of CBUs. However, the exclusion policies (based on these test results) vary among nations and institutions. We tested 28,000 processed CBUs between May 2006 and June 2014. The cord blood leukocytes from CMV IgM-positive samples were then subjected to NAT. The total nucleated cell and CD34+ cell counts were measured for each CBU, and the results were compared to the CMV IgM and IgG results. The seroprevalence of CMV among pregnant women was 98.1% (18,459/18,818) for IgG and 1.7% (441/25,293) for IgM. The concentration and the total number of CD34+ cells were significantly higher in CBUs from IgM-negative mothers compared to those from IgM-positive mothers (72.4/μl vs. 57.2/μl, respectively, p < 0.0001; 1.45 × 106/unit vs. 1.15 × 106/unit, respectively, p < 0.0001). Among CBUs with positive CMV IgM in their mothers' plasma or cord blood plasma, only 0.58% of the samples (3/517) had a positive NAT. The number of excluded CBUs from inventory due to positive CMV IgM in the cord blood was 54 of 18,326 (0.3%). For inventory purposes, it is appropriate to remove CBUs with positive cord blood CMV IgM findings irrespective of the NAT status as well as positive maternal CMV IgM in South Korea.

Patterns of Biomarkers in Cord Blood During Pregnancy and Preeclampsia.

Science.gov (United States)

Kharb, S; Nanda, S

2017-01-01

Umbilical cord blood (UCB) is in contact with all the fetal tissues and can reflect the state of fetus and UCB can be compared with maternal blood. Inflammatory, metabolic and immunological disorders during pregnancy can affect the environment in which the fetus is developing and may produce various alterations. To analyze different biochemical parameters in maternal venous blood and new born umbilical cord blood from healthy normotensive pregnant and preeclamptic women. Homocysteine, folate, B12, heme oxygenase-1 (HO-1), endoglin, leptin, cholinesterase, IGF-1, Apo A, lipoproteins, TSH, fT3, fT4 were analyzed in maternal sera and venous umbilical cord sera of newborns of twenty five preeclamptics (group II) and twenty five normotensive pregnant women (group I). Homocysteine, folic acid, vitamin B12, Apo A I & II, TSH, fT3, fT4 levels were estimated by competitive immunoassay using direct chemiluminiscence technology. Heme oxygenase-1 (HO-1), endoglin, leptin, cholinesterase, IGF-1 were analyzed by ELISA. Maternal and cord blood levels of homocysteine, folic acid, lipid profile (namely, total cholesterol, triglycerides, LDL-C, VLDL-C and HDL-C), TSH, heme oxygenase 1, were higher in preeclamptic women as compared to normotensive pregnant women. Endoglin levels were significantly lower in cord blood of preeclamptic mother as compared to normotensive mothers. Serum and cord blood vitamin B12, Apo A-I and Apo B l, cholinesterase, leptin levels, IGF-I were lower in preeclamptic women as compared to normotensive pregnant. Findings of the present study suggest that biochemical alterations occur in mothers and fetuses and modifications of uterine environment (in terms of thyroxine and folate and vitamin B12 supplementation) can be of help. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Functional Recovery Secondary to Neural Stem/Progenitor Cells Transplantation Combined with Treadmill Training in Mice with Chronic Spinal Cord Injury

DEFF Research Database (Denmark)

Tashiro, Syoichi; Nishimura, Soraya; Iwai, Hiroki

are chiefly developed to improve the effect of regenerative therapy for this refractory state, physical training also have attracted the attention as a desirable candidate to combine with cell transplantation. Recently, we have reported that the addition of treadmill training enhances the effect of NS...... in the combined therapy group. Further investigation revealed that NS/PC transplantation improved spinal conductivity and central pattern generator activity, and that training promoted the appropriate inhibitory motor control including spasticity. The combined therapy enhanced these independent effects of each......Rapid progress in stem cell medicine is being realized in neural regeneration also in spinal cord injury (SCI). Researchers have reported remarkable functional recovery with various cell sources including induced Pluripotent Stem cell derived neural stem/progenitor cells (NS/PCs), especially...

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.

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

Antenatal steroid exposure in the late preterm period is associated with reduced cord blood neurotrophin-3.

Science.gov (United States)

Hodyl, Nicolette A; Crawford, Tara M; McKerracher, Lorna; Lawrence, Andrew; Pitcher, Julia B; Stark, Michael J

2016-10-01

Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population. To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure. Retrospective analysis. Late preterm infants (33-36weeks; n=119) and term infants (37-41weeks; n=129) born at the Women's and Children's Hospital, Adelaide. Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA. Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p24h prior to delivery (p<0.01). This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessing the bipotency of in vitro-derived neuromesodermal progenitors [v1; ref status: indexed, http://f1000r.es/58z

Directory of Open Access Journals (Sweden)

Anestis Tsakiridis

2015-04-01

Full Text Available Retrospective clonal analysis in the mouse has demonstrated that the posterior spinal cord neurectoderm and paraxial mesoderm share a common bipotent progenitor. These neuromesodermal progenitors (NMPs are the source of new axial structures during embryonic rostrocaudal axis elongation and are marked by the simultaneous co-expression of the transcription factors T(Brachyury (T(Bra and Sox2. NMP-like cells have recently been derived from pluripotent stem cells in vitro following combined stimulation of Wnt and fibroblast growth factor (FGF signaling. Under these conditions the majority of cultures consist of T(Bra/Sox2 co-expressing cells after 48-72 hours of differentiation. Although the capacity of these cells to generate posterior neural and paraxial mesoderm derivatives has been demonstrated at the population level, it is unknown whether a single in vitro-derived NMP can give rise to both neural and mesodermal cells. Here we demonstrate that T(Bra positive cells obtained from mouse epiblast stem cells (EpiSCs after culture in NMP-inducing conditions can generate both neural and mesodermal clones. This finding suggests that, similar to their embryonic counterparts, in vitro-derived NMPs are truly bipotent and can thus be exploited as a model for studying the molecular basis of developmental cell fate decisions.

Effects of cord compression on fetal blood flow distribution and O2 delivery

International Nuclear Information System (INIS)

Itskovitz, J.; LaGamma, E.F.; Rudolph, A.M.

1987-01-01

The authors used the radionuclide microsphere technique in nine fetal lambs to examine the effect of partial cord compression on distribution of cardiac output and O 2 delivery to fetal organs and venous flow patterns. With a 50% reduction in umbilical blood flow the fraction of fetal cardiac output distributed to the brain, heart, carcass, kidneys, and gastrointestinal tract increased. Pulmonary blood flow fell. O 2 delivery to the brain and myocardium was maintained but was reduced to peripheral, renal, and gastrointestinal circulations. Hepatic blood flow decreased and O 2 delivery fell by 75%. The proportion of umbilical venous blood passing through the ductus venosus increased from 43.9 to 71.8%. The preferential distribution of ductus venosus blood flow through the foramen ovale was enhanced and the proportion of O 2 delivery to upper body organs derived from the ductus venosus increased. Abdominal inferior vena caval blood flow increased, and it was also preferentially distributed through the foramen ovale and constituted the major fraction of the arterial blood supply to the upper body organs. Thus cord compression modified the distribution of cardiac output and the patterns of venous returns in the fetus. This pattern of circulatory response differs from that observed with other causes of reduced O 2 delivery

Decreased cord-blood phospholipids in young age-at-onset type 1 diabetes.

Science.gov (United States)

La Torre, Daria; Seppänen-Laakso, Tuulikki; Larsson, Helena E; Hyötyläinen, Tuulia; Ivarsson, Sten A; Lernmark, Ake; Oresic, Matej

2013-11-01

Children developing type 1 diabetes may have risk markers already in their umbilical cord blood. It is hypothesized that the risk for type 1 diabetes at an early age may be increased by a pathogenic pregnancy and be reflected in altered cord-blood composition. This study used metabolomics to test if the cord-blood lipidome was affected in children diagnosed with type 1 diabetes before 8 years of age. The present case-control study of 76 index children diagnosed with type 1 diabetes before 8 years of age and 76 healthy control subjects matched for HLA risk, sex, and date of birth, as well as the mother's age and gestational age, revealed that cord-blood phosphatidylcholines and phosphatidylethanolamines were significantly decreased in children diagnosed with type 1 diabetes before 4 years of age. Reduced levels of triglycerides correlated to gestational age in index and control children and to age at diagnosis only in the index children. Finally, gestational infection during the first trimester was associated with lower cord-blood total lysophosphatidylcholines in index and control children. In conclusion, metabolomics of umbilical cord blood may identify children at increased risk for type 1 diabetes. Low phospholipid levels at birth may represent key mediators of the immune system and contribute to early induction of islet autoimmunity.

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.

Erythrocyte enrichment in hematopoietic progenitor cell cultures based on magnetic susceptibility of the hemoglobin.

Directory of Open Access Journals (Sweden)

Xiaoxia Jin

Full Text Available Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A, hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes.

A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells

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Richard Longeras

2012-01-01

Full Text Available Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs. Pigment epithelium-derived factor (PEDF contains an N-terminal 34-amino acid peptide (PEDF-34 that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+ cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS. OIR significantly increased the number of circulating Tie2-GFP+ at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+ cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+ cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.

Umbilical Cord Blood Lead Levels and Neonatal Behaviour

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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.

Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures

NARCIS (Netherlands)

L.E. Duinhouwer (Lucia); N. Tüysüz (Nesrin); E.J. Rombouts (Elwin); M.N.D. Ter Borg (Mariëtte N. D.); E. Mastrobattista; J. Spanholtz (Jan); J.J. Cornelissen (Jan); D. ten Berge (Derk); E. Braakman (Eric)

2015-01-01

textabstractAbstract Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach to improve insufficient engraftment after umbilical cord blood stem cell transplantation (UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in

Congenital hypothyroidism screening in term neonates using umbilical cord blood TSH values

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Ravi Bhatia

2018-01-01

Full Text Available Congenital hypothyroidism remains one of the most common preventable causes of mental retardation among children. Screening for congenital hypothyroidism remains one of the most cost-effective tools to prevent mental retardation in the population. Umbilical cord blood thyroid-stimulating hormone (TSH levels remain an attractive and a practical step for screening for congenital hypothyroidism. The aims of this study were as follows: (1 to find normative values of cord blood TSH for the study group and (2 to use cord blood TSH levels as a marker for screening of congenital hypothyroidism. Cord blood of 1824 neonates who were of term gestation, weighed >2.5 kg at birth, whose mothers were off thyroid medication were a part of the study group. Umbilical cord blood was collected at the time of delivery and TSH was estimated. All babies who had a cord blood TSH value of >20 mIU/L were called bay on day 7 of life for a full thyroid profile. Cord blood samples of 1824 neonates were tested for TSH. Male–female ratio was 979:845 = 1.15:1. The birth weights ranged between 2.5 and 4.5 kg with an average birth weight of 2.811 kg. Mean (standard deviation TSH value was 7.725 (8.99. TSH values ranged between 1.2 and 100 mIU/ml. TSH values corresponding to the 3rd, 10th, 25th, 50th, 90th, 95th, and 97th percentile were 2.32, 4.05, 5.67, 7.5, 12, 20.63, and 30.88, respectively. Out of the 88 babies recalled for repeat testing, 80 babies only turned up; eventually one turned out to be hypothyroid on repeat testing. The incidence of congenital hypothyroidism in our study was 1 in 1824. To conclude, we can safely use a cutoff of cord blood TSH value of >20 mIU/L for the purpose of screening for congenital hypothyroidism. For logistic angles, a higher cutoff of >30 mIU/L can be used. Large population-based studies are required to establish normative values for cord blood TSH in our country.

Spinal cord blood flow measured by 14C-iodoantipyrine autoradiography during and after graded spinal cord compression in rats

International Nuclear Information System (INIS)

Holtz, A.; Nystroem, B.G.; Gerdin, B.

1989-01-01

The relations between degree of thoracic spinal cord compression causing myelographic block, reversible paraparesis, and extinction of the sensory evoked potential on one hand, and spinal cord blood flow on the other, were investigated. This was done in rats using the blocking weight-technique and 14 C-iodoantipyrine autoradiography. A load of 9 g caused myelographic block. Five minutes of compression with that load caused a reduction of spinal cord blood flow to about 25%, but 5 and 60 minutes after the compression spinal cord blood flow was restored to 60% of the pretrauma value. A load of 35 g for 5 minutes caused transient paraparesis. Recovery to about 30% was observed 5 and 60 minutes thereafter. During compression at a load of 55 g, which caused almost total extinction of sensory evoked potential and irreversible paraplegia, spinal cord blood flow under the load ceased. The results indicate that myelographic block occurs at a load which does not cause irreversible paraparesis and that a load which permits sensory evoked potential to be elicited results in potentially salvageable damage

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

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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

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

International Nuclear Information System (INIS)

Llop, Sabrina; Aguinagalde, Xabier; Vioque, Jesus; Ibarluzea, Jesus; Guxens, Monica; Casas, Maribel; Murcia, Mario; Ruiz, Maria

2011-01-01

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 μg/dL). Results: A low percentage of cord blood samples with lead levels ≥ 2 μg/dL were found (5.9%). Geometric mean and maximum were 1.06 μg/dL and 19 μg/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 μg/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: → Pb is a ubiquitous environmental pollutant with harmful effects on neurodevelopment. → Cord blood Pb levels in Spanish newborn are low in

Magnetic resonance detection of CD34+ cells from umbilical cord blood using a 19F label

NARCIS (Netherlands)

L.E. Duinhouwer (Lucia); Van Rossum, B.J.M. (Bernard J. M.); S.T. van Tiel (Sandra); R.M. van der Werf (Ramon); R.Q. Doeswijk (Ronald); J.C. Haeck (Joost); Rombouts, E.W.J.C. (Elwin W. J. C.); M.N.D. Ter Borg (Mariëtte N. D.); G. Kotek (Gyula); E. Braakman (Eric); J.J. Cornelissen (Jan); M.R. Bernsen (Monique)

2015-01-01

textabstractImpaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and

Effects of cytokine combinations on the cell cycle and early apoptosis of irradiated umbilical cord blood AC133+ cells

International Nuclear Information System (INIS)

Liu Yulong; Dai Hong; Jiang Zhong; Zhou Liying; Guo Xiaokui; Zhou Jianying

2005-01-01

The cell cycle and early apoptosis of 2.5 Gy 6 MV-X ray irradiated umbilical cord blood AC133 + cells cultured with cytokine combinations (IL-3 + FL + SCF) were immunolabelled and analyzed by flow cytometry at d 0, 1, 2, 3 and 7. The result of flow cytometry analysis showed that majority of irradiated umbilical cord blood AC133 + cells were in G 0 /G 1 phase of the cell cycle at d 0. Under the influence of cytokine combinations (IL-3 + FL + SCF), nearly 50% of cells were in S phase on 3rd day. AC133 + cells irradiated were in vitro incubated in the medium without cytokines, nearly all cells died by apoptosis. However, when we incubated cells with cytokine combinations (IL-3 + FL + SCF), (38.0 ± 6.8)% of cells were saved from apoptosis at d 2. The more percent of saved AC133 + cells became to proliferate with the extension of culture. In short, cytokine combinations (IL-3 + FL + SCF) could have a key role to protect irradiated cells and partially avoid induction of apoptosis by ionizing radiation in hematopoietics stem/progenitor cells. (authors)

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

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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.

Differential gene expresison in umbilical cord blood and maternal peripheral blood

Czech Academy of Sciences Publication Activity Database

Merkerová, M.; Vasiková, A.; Bruchová, H.; Líbalová, Helena; Topinka, Jan; Balaščak, I.; Šrám, Radim; Brdička, R.

2009-01-01

Roč. 83, č. 3 (2009), s. 183-190 ISSN 0902-4441 R&D Projects: GA MŠk 2B06088 Institutional research plan: CEZ:AV0Z50390512 Keywords : gene expression * umbilical cord blood * peripheral blood Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.345, year: 2009

Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures

NARCIS (Netherlands)

Duinhouwer, Lucia E.; Tüysüz, Nesrin; Rombouts, Elwin W J C; Ter Borg, Mariette N D; Mastrobattista, Enrico; Spanholtz, Jan; Cornelissen, Jan J.; Berge, Derk Ten; Braakman, Eric

2015-01-01

Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach to improve insufficient engraftment after umbilical cord blood stem cell transplantation (UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in robust proliferation, it is accompanied with

Correlation of routine haematological parameters between normal maternal blood and the cord blood of healthy newborns in selected hospitals of karachi

International Nuclear Information System (INIS)

Qaiser, D.H.; Ghori, G.M.; Sandila, M.P.; Omair, A.

2013-01-01

Objective: To determine any significant correlation between the routine haematological parameters of maternal blood and umbilical cord blood of their respective newborns. Study Design: Cross sectional study. Place and Duration of Study: The study was conducted at four public and private hospitals of Karachi including Sindh Government Qatar Hospital, Sindh Government Hospital, Liaquatabad, Ziauddin University Hospital and Chinniot Maternity and Child Hospital, respectively from July 2006 to April 2008. Methodology: Three milliliters venous blood was collected in EDTA containing tube for complete blood count of mothers before delivery. Five milliliters cord blood was collected from the umbilical cord of the babies immediately after delivery by clamping and cutting the babies' end of the cord. For haematological parameters a standard coultergram was done including haemoglobin, RBCs count, haematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cell count, differential leukocyte count and platelet count. Pearson's correlation co-efficient was used to determine an association between the maternal and cord blood parameters. Results: A total of 404 maternal and umbilical cord blood samples were analyzed. All the blood parameters including haemoglobin, RBCs count, HCT, MCV, MCH, white blood cell count, differential leukocyte count and platelet count were found to be high in cord blood as compared to the maternal blood, but they showed a very weak to negligible correlation. Mean Corpuscular Haemoglobin Concentration (MCHC), showed a moderate correlation. Conclusion: Routine haematological parameters of newborns are independent of maternal routine haematological parameters. (author)

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

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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.

Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

Science.gov (United States)

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

International Nuclear Information System (INIS)

Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae; Chang, Jong Wook; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Kim, Jae-Sung; Jeon, Hong Bae

2014-01-01

Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications

Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Chang, Jong Wook [Research Institute for Future Medicine Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710 (Korea, Republic of); Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Kim, Jae-Sung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Jeon, Hong Bae, E-mail: jhb@medi-post.co.kr [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of)

2014-04-18

Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

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

2017-07-01

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.

Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

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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.

Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hindlimb Ischemia through Enhancing Angiogenesis in Tree Shrews

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Cunping Yin

2016-01-01

Full Text Available Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

Increased Cord Blood Betatrophin Levels in the Offspring of Mothers with Gestational Diabetes

Science.gov (United States)

Wu, Shimin; Zhao, Yue; Du, Caiqi; Yuan, Guandou; Ning, Qin; McCormick, Kenneth; Luo, Xiaoping

2016-01-01

Aim Exposing a fetus to hyperglycemia can increase the risk for later-life metabolic disorders. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. Highly responsive to nutritional signals, serum betatrophin concentrations have been found to be altered by various physiological and pathological conditions. We hypothesized that betatrophin levels are increased in the cord blood in offspring exposed to intrauterine hyperglycemia. Methods This was a cross-sectional study including 54 mothers who underwent uncomplicated Cesarean delivery in a university hospital. Maternal gestational glucose concentration was determined at 24–48 weeks gestation after a 75-g OGTT. Cord blood and placental tissue was collected immediately post delivery. Metabolic parameters were determined in the Clinical Laboratory. Cord blood betatrophin levels were assayed using a commercially available ELISA kit. Placental mitochondrial content was determined by real-time PCR. Results Cord blood betatrophin levels were increased in the gestational diabetes mellitus (GDM) group compared with the normoglycemic group. Furthermore, betatrophin levels were positively correlated with maternal gestational 2h post-OGTT glucose, cord blood insulin, HOMA-IR, and inversely correlated with placental mitochondrial content. Conclusions Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of GDM on offspring. PMID:27196053

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

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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. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

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

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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.

The effect of the colostral cells on gene expression of cytokines in cord blood cells.

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Hrdý, Jiří; Novotná, Olga; Kocourková, Ingrid; Prokešová, Ludmila

2017-11-01

Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.

Conditioned Media from Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibits Melanogenesis by Promoting Proteasomal Degradation of MITF.

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Eun Sung Kim

Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

The relationship between cord blood immunoglobulin E levels and allergy-related outcomes in young adults.

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Shah, Purvee S; Wegienka, Ganesa; Havstad, Suzanne; Johnson, Christine Cole; Ownby, Dennis R; Zoratti, Edward M

2011-03-01

Elevated cord blood IgE may be associated with a higher risk of allergic disease. To determine whether cord blood IgE is associated with allergic biomarkers or allergic disorders in young adults. Data was collected from 670 subjects 18-21 years of age that were among 835 original participants in the Detroit Childhood Allergy Study, a general risk, population-based birth cohort. Cord blood IgE was assessed in relation to biomarkers associated with allergy and asthma including total IgE, allergen-specific IgE, blood eosinophilia, and spirometry. Cord blood IgE was also analyzed for associations to subsequent allergic disease including atopic dermatitis, allergic rhinitis, and asthma. Cord blood IgE, analyzed as a continuous measure, was modestly correlated with total IgE (r = 0.18, P Immunology. Published by Elsevier Inc. All rights reserved.

Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

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Nicolas Christoforou

Full Text Available The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS cells, which once differentiated allow for the enrichment of Nkx2-5(+ cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+ cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological

Fostering public cord blood banking and research in Canada.

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Isasi, Rosario; Dalpe, Gratien; Knoppers, Bartha M

2013-12-01

In June 2013, Canadian Blood Services (CBS) established the National Public Cord Blood Bank (NPCBB) accessible to Canadian and international patients and researchers. The NPCBB promotes efforts that contribute to research and improved clinical care by making units not suitable for banking or transplantation available for research. In the context of the NPCBB of the CBS, this article will focus on the practical tools (e.g., consent protocols) developed to optimize umbilical cord blood (UCB) banking and research while enabling ethical provenance of UCB stem cells. The Canadian approach represents an ideal model for comparison as it is a country in which the national public bank (and other regional/provincial public banks) coexists with private companies.

Evaluation of the impact of banking umbilical cord blood units with high cell dose for ethnically diverse patients.

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Stritesky, Gretta; Wadsworth, Kimberly; Duffy, Merry; Buck, Kelly; Dehn, Jason

2018-02-01

Umbilical cord blood units provide an important stem cell source for transplantation, particularly for patients of ethnic diversity who may not have suitably matched available, adult-unrelated donors. However, with the cost of cord blood unit acquisition from public banks significantly higher than that for adult-unrelated donors, attention is focused on decreasing cost yet still providing cord blood units to patients in need. Historical practices of banking units with low total nucleated cell counts, including units with approximately 90 × 10 7 total nucleated cells, indicates that most banked cord blood units have much lower total nucleated cell counts than are required for transplant. The objective of this study was to determine the impact on the ability to identify suitable cord blood units for transplantation if the minimum total nucleated cell count for banking were increased from 90 × 10 7 to 124 or 149 × 10 7 . We analyzed ethnically diverse patients (median age, 3 years) who underwent transplantation of a single cord blood unit in 2005 to 2016. A cord blood unit search was evaluated to identify units with equal or greater human leukocyte antigen matching and a greater total nucleated cell count than that of the transplanted cord blood unit (the replacement cord blood unit). If the minimum total nucleated cell count for banking increased to 124 or 149 × 10 7 , then from 75 to 80% of patients would still have at least 1 replacement cord blood unit in the current (2016) cord blood unit inventory. The best replacement cord blood units were often found among cords with the same ethnic background as the patient. The current data suggest that, if the minimum total nucleated cell count were increased for banking, then it would likely lead to an inventory of more desirable cord blood units while having minimal impact on the identification of suitable cord blood units for transplantation. © 2017 AABB.

Arterial cord blood lactate at birth correlates with duration of pushing efforts.

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Dessolle, Lionel; Lebrec, Jeremie; Daraï, Emile

2010-01-01

To evaluate the impact of the duration of pushing efforts on arterial cord blood lactate values. This was a prospective observational study of 124 consecutive normal vaginal deliveries in a tertiary teaching hospital. Arterial cord blood lactate was determined immediately at birth with a test strip method. Univariate and multivariate analyses were performed to check for clinical determinants of lactate levels. The main measure was lactate according to the duration of pushing efforts. Arterial cord lactates increased significantly and were strongly correlated with the duration of pushing efforts, independent of gestational age and birthweight. Women pushing for more than 20 min had higher arterial cord blood lactates (4.9 +/- 1.4 vs. 3.3 +/- 1.16 mM, respectively) and a higher rate of lactates >6 mM (18 vs. 3%) than those pushing for less than 20 min. At normal delivery, arterial cord blood lactates increase significantly with the duration of pushing efforts. Pushing for more than 20 min is associated with an increased risk of metabolic acidosis in the neonate. Further studies are required to evaluate the clinical significance of these observations. 2009 S. Karger AG, Basel.

Cord blood full blood count parameters in Lagos, Nigeria | Adewumi ...

African Journals Online (AJOL)

Due to its usefulness in the assessment of health status of individuals, its parameters in cord blood, a major source of haemopoietic stem cell transplantation and an ideal source for laboratory investigations for newborns were determined to provide a useful guide to local neonatologists and stem cell transplant physicians.

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 usi...... ROC-curves, where an ABE value less than -12 was used as "gold standard" for significant intrapartum asphyxia.......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...

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks.

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Magalon, Jeremy; Maiers, Martin; Kurtzberg, Joanne; Navarrete, Cristina; Rubinstein, Pablo; Brown, Colin; Schramm, Catherine; Larghero, Jérome; Katsahian, Sandrine; Chabannon, Christian; Picard, Christophe; Platz, Alexander; Schmidt, Alexander; Katz, Gregory

2015-01-01

Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies. Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit. When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long term. We also found that

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks

Science.gov (United States)

Magalon, Jeremy; Maiers, Martin; Kurtzberg, Joanne; Navarrete, Cristina; Rubinstein, Pablo; Brown, Colin; Schramm, Catherine; Larghero, Jérome; Katsahian, Sandrine; Chabannon, Christian; Picard, Christophe; Platz, Alexander; Schmidt, Alexander; Katz, Gregory

2015-01-01

Background Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies. Methods Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit. Results When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks.

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Jeremy Magalon

Full Text Available Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies.Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts. 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A to the most selective (scenario D. We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit.When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted along with the highest financial deficit (USD 5.89 million. We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million that charities and public health could realistically finance over the long term. We also

Umbilical cord blood-derived natural killer cells combined with Bevacizumab for colorectal cancer treatment.

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Xu, Chen; Liu, Dongning; Chen, Zhixin; Zhuo, Fan; Sun, Huankui; Hu, Jiaping; Li, Taiyuan

2018-06-19

Colorectal cancer (CRC) is among cancers with highest incidence globally and currently ranks fourth as the leading cause of cancer-related deaths worldwide. It remains an urgent need for novel strategies in the management of patients with advanced CRC. Adoptive transfer of allogeneic natural killer (NK) cells represent an attractive option in the treatment of patients with CRC. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound IL-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of IFN-γ, TNF-α, GM-CSF and CCL3 compared with IL-2 stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. More NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Combination of bevacizumab can increase extravasation of adoptively transferred NK cells into the LoVo tumors and improve the therapeutic activity of eUCB-NK cells. These results justified clinical translation of this UCB-derived NK cell-based therapeutics, either used alone or combined with bevacizumab, as a novel treatment option for patients with CRC.

Proteomic Profiling of Ex Vivo Expanded CD34-Positive Haematopoetic Cells Derived from Umbilical Cord Blood

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Heiner Falkenberg

2013-01-01

Full Text Available Ex vivo expansion of haematopoetic cells by application of specific cytokines is one approach to overcome boundaries in cord blood transplantation due to limited numbers of haematopoetic stem cells. While many protocols describe an effective increase of total cell numbers and the amount of CD34-positive cells, it still remains unclear if and how the procedure actually affects the cells’ properties. In the presented publications, CD34-positive cells were isolated from cord blood and expanded for up to 7 days in media supplemented with stem cell factor (SCF, thrombopoietin (THPO, interleukin 6 (IL-6, and fms-related tyrosine kinase 3 ligand (FLT3lg. At days 3 and 7, expanded cells were harvested and analyzed by flow cytometry and quantitative proteomics. 2970 proteins were identified, whereof proteomic analysis showed 440 proteins significantly changed in abundance during ex vivo expansion. Despite the fact that haematopoetic cells still expressed CD34 on the surface after 3 days, major changes in regard to the protein profile were observed, while further expansion showed less effect on the proteome level. Enrichment analysis of biological processes clearly showed a proteomic change toward a protein biosynthesis phenotype already within the first three days of expression.

Complete Blood Count Reference Values of Cord Blood in Taiwan and the Influence of Gender and Delivery Route on Them

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Yu-Hsun Chang

2011-06-01

Conclusion: We successfully obtained the normal CBC and WBC DC reference values of the cord blood in Taiwan. Gender and delivery routes were important confounding factors that influenced the cord blood CBC and WBC DC values.

[THE USE AND STORAGE OF STEM CELLS AND CORD BLOOD: FRENCH AND ENGLISH LAW COMPARATIVE APPROACH].

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Madanamoothoo, Allane

2015-07-01

Becoming parents is one of the greatest wishes of a lot of couples. When their dreams come true, prior to the birth of the child, parents have to face several points: the choice of the name, place of delivery, breast or bottle feeding, etc. Recently, they have to face the issues of cord blood stem cells. Researchers and cord blood banks are also interested in those cells. In many countries a lot of advertising is made around umbilical cord blood stem cells. In France as in England, the use and preservation of cord blood are regulated by the legislators without necessarily having the same approach. The objective of this paper is to present English and French law approaches' on cord blood stem cells.

Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

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Elvira Pelosi

Full Text Available Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-, triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45- capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

Inflammatory markers in umbilical cord blood from small-for-gestational-age newborns

DEFF Research Database (Denmark)

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

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...

Relationship between cord blood IGF-I, IGFBP-3 levels and intrauterine growth retardation (IUGR)

International Nuclear Information System (INIS)

Yu Suqing; Chu Kaiqiu; Chen Shengjie

2008-01-01

Objective: To study the cord blood insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) levels in neonates with intrauterine growth retardation (IUGR). Methods: Cord serum IGF-I (with RIA) and IGFBP-3 (with IRMA) levels were measured in 22 neonates with IUGR and 64 neonates with appropriate gestational age (AGA). Results: Cord blood IGF-I and IGFBP-3 levels in IUGR neonates were significantly lower than those in AGA neonates (P<0.001). Among the 86 neonates studied in this article, 44 were born pre-term and 42 were born full term. From the data, we could see that the cord blood IGF-I and IGFBP-3 levels in pre-term neonates were significantly lower than those in full-term neonates (P also <0.001). IGF-I and IGFBP-3 levels were mutually positively correlated (P<0.01). Conclusion: Cord blood IGF-I and IGFBP-3 levels were useful indicator of neonates growth. (authors)

Use of autologous blood-derived endothelial progenitor cells at point-of-care to protect against implant thrombosis in a large animal model.

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Jantzen, Alexandra E; Lane, Whitney O; Gage, Shawn M; Jamiolkowski, Ryan M; Haseltine, Justin M; Galinat, Lauren J; Lin, Fu-Hsiung; Lawson, Jeffrey H; Truskey, George A; Achneck, Hardean E

2011-11-01

Titanium (Ti) is commonly utilized in many cardiovascular devices, e.g. as a component of Nitinol stents, intra- and extracorporeal mechanical circulatory assist devices, but is associated with the risk of thromboemboli formation. We propose to solve this problem by lining the Ti blood-contacting surfaces with autologous peripheral blood-derived late outgrowth endothelial progenitor cells (EPCs) after having previously demonstrated that these EPCs adhere to and grow on Ti under physiological shear stresses and functionally adapt to their environment under flow conditions ex vivo. Autologous fluorescently-labeled porcine EPCs were seeded at the point-of-care in the operating room onto Ti tubes for 30 min and implanted into the pro-thrombotic environment of the inferior vena cava of swine (n = 8). After 3 days, Ti tubes were explanted, disassembled, and the blood-contacting surface was imaged. A blinded analysis found all 4 cell-seeded implants to be free of clot, whereas 4 controls without EPCs were either entirely occluded or partially thrombosed. Pre-labeled EPCs had spread and were present on all 4 cell-seeded implants while no endothelial cells were observed on control implants. These results suggest that late outgrowth autologous EPCs represent a promising source of lining Ti implants to reduce thrombosis in vivo. Copyright © 2011 Elsevier Ltd. All rights reserved.

Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

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Shinobu Tsuzuki

2007-05-01

Full Text Available AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo.These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood

Birth Weight, Cord Blood Lipoprotein and Apolipoprotein Levels in Indian Newborns

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Simmi Kharb

2010-01-01

Full Text Available Objectives: Primordial prevention of chronic disease is of clinical andpublic health importance. Considering the fetal onset of atherosclerosis,we aimed to determine the cord blood level of lipoproteins andapolipoproteins as well as their correlation with birth weight and gestationalage.Methods: This cross-sectional study comprised 100 healthy Indiannewborns. Ten ml. of cord blood was collected from placental end ofumbilical vein. Serum was separated by centrifugation and analyzed onthe same day for lipid profile including total cholesterol (TC, triglycerides(TG, high density lipoprotein- cholesterol (HDL-C, very lowdensity lipoprotein-cholesterol (VLDL and low density lipoproteincholesterol(LDL-C, apolipoproteins A-I and B (ApoA-I, ApoB.Atherogenic index (AI was calculated as the ratio of ApoB to ApoA-I.Results: Cord blood of female newborns had higher TC, HDL-C,LDL-C, Apo A-I, Apo B and AI as compared to male newborns,whereas TG and VLDL-C were higher in male than in female newborns.Significant positive correlation was observed between cordblood Apo A-I and HDL-C (r= 0.45, p0.05.Conclusions: These findings are another confirmatory evidence forthe association of prenatal factors with cord blood lipid profile, andcan serve as starting point for studying lipid transport system changesduring early life.

Pregnant women's knowledge and attitudes about stem cells and cord blood banking.

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Dinç, H; Sahin, N H

2009-06-01

This study was to determine pregnant women's knowledge and attitudes towards stem cells and cord blood banking in Istanbul, Turkey. Stem cell research is one of the most important and, at the same time, the most controversial topics of science and technology today. Nurses need to understand stem cell research so they can enter the debate on this issue. They can become important sources of information in order to help parents understand the issues. This exploratory descriptive study was conducted in two antenatal outpatient clinics in Istanbul. The sample consisted of 334 pregnant women during routine prenatal visits. Data were collected in interviews by using an interview form developed by the researchers according to the literature. The form included demographic characteristics of participants and 20 questions about stem cells, storing cord blood and banking and 10 independent attitude statements. The majority of the participants had a lack of knowledge about stem cells and cord blood banking and wanted more information. Before pregnancy, they received some information through the media (newspaper, Internet, television, etc.), but unintentionally. It was determined that they wanted information before becoming pregnant, more from their obstetrician but also from nurses and midwives. The majority also wanted to store their infants' cord blood and stated that they would be more likely to choose a public cord blood bank. Those giving ante- and perinatal care need to offer accurate and scientific counselling services on this subject to parents who need to be informed.

Angiogenic Factors in Cord Blood of Preterm Infants Predicts Subsequently Developing Bronchopulmonary Dysplasia

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Wen-Chien Yang

2015-12-01

Conclusion: Cord blood level of PlGF, rather than VEGF or sFlt-1, was significantly increased in the BPD group. Consistent with our previous report, cord blood level of PlGF may be considered as a biomarker to predict subsequently developing BPD in preterm infants.

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.; Iglesias, D.; Nicola, F.C.; Steffens, D.; Valentim, L.; Witczak, A.; Zanatta, G.; Achaval, M.; Pranke, P.; Netto, C.A.

2011-01-01

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

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.

Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury

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Geissler, Sydney A.; Sabin, Alexandra L.; Besser, Rachel R.; Gooden, Olivia M.; Shirk, Bryce D.; Nguyen, Quan M.; Khaing, Zin Z.; Schmidt, Christine E.

2018-04-01

Objective. Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. Approach. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Main results. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group. Significance. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

Human Cord Blood and Bone Marrow CD34+ Cells Generate Macrophages That Support Erythroid Islands.

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Eyayu Belay

Full Text Available Recently, we developed a small molecule responsive hyperactive Mpl-based Cell Growth Switch (CGS that drives erythropoiesis associated with macrophages in the absence of exogenous cytokines. Here, we compare the physical, cellular and molecular interaction between the macrophages and erythroid cells in CGS expanded CD34+ cells harvested from cord blood, marrow or G-CSF-mobilized peripheral blood. Results indicated that macrophage based erythroid islands could be generated from cord blood and marrow CD34+ cells but not from G-CSF-mobilized CD34+ cells. Additional studies suggest that the deficiency resides with the G-CSF-mobilized CD34+ derived monocytes. Gene expression and proteomics studies of the in vitro generated erythroid islands detected the expression of erythroblast macrophage protein (EMP, intercellular adhesion molecule 4 (ICAM-4, CD163 and DNASE2. 78% of the erythroblasts in contact with macrophages reached the pre reticulocyte orthochromatic stage of differentiation within 14 days of culture. The addition of conditioned medium from cultures of CD146+ marrow fibroblasts resulted in a 700-fold increase in total cell number and a 90-fold increase in erythroid cell number. This novel CD34+ cell derived erythroid island may serve as a platform to explore the molecular basis of red cell maturation and production under normal, stress and pathological conditions.

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

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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.

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.

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Watson, P Marc D; Paterson, Judy C; Thom, George; Ginman, Ulrika; Lundquist, Stefan; Webster, Carl I

2013-06-18

Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS

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

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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.

Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank.

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Wang, Tso-Fu; Wen, Shu-Hui; Yang, Kuo-Liang; Yang, Shang-Hsien; Yang, Yun-Fan; Chang, Chu-Yu; Wu, Yi-Feng; Chen, Shu-Huey

2014-01-01

To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3-year recruitment period. We analyzed records of the reasons for exclusion of the potential UCB donation from 2004 to 2006 in the Tzu-Chi Cord Blood Bank and compared the results over 3 years. We grouped these reasons for exclusion into five phases, before collection, during delivery, before processing, during processing, and after freezing according to the time sequence and analyzed the reasons at each phase. Between 2004 and 2006, there were 10,685 deliveries with the intention of UCB donation. In total, 41.2% of the UCB units were considered eligible for transplantation. The exclusion rates were 93.1, 48.4, and 54.1% in 2004, 2005, and 2006, respectively. We excluded 612 donations from women before their child birth, 133 UCB units during delivery, 80 units before processing, 5010 units during processing, and 421 units after freezing. There were 24 UCB units with unknown reasons of ineligibility. Low UCB weight and low cell count were the first two leading causes of exclusion (48.6 and 30.9%). The prevalence of artificial errors, holiday or transportation problem, low weight, and infant problems decreased year after year. The exclusion rate was high at the beginning of our study as in previous studies. Understanding the reasons for UCB exclusion may help to improve the efficiency of UCB banking programs in the future. © 2013 American Association of Blood Banks.

High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies.

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Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Laplanche, Agnès; Hartmann, Olivier; Vassal, Gilles; Farace, Françoise

2009-07-15

Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow-derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P < 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors

Optimising methods of red cell sedimentation from cord blood to maximise nucleated cell recovery prior to cryopreservation.

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Madkaikar, M; Gupta, M; Ghosh, K; Swaminathan, S; Sonawane, L; Mohanty, D

2007-01-01

Human cord blood is now an established source of stem cells for haematopoietic reconstitution. Red blood cell (RBC) depletion is required to reduce the cord blood unit volume for commercial banking. Red cell sedimentation using hydroxy ethyl starch (HES) is a standard procedure in most cord blood banks. However, while standardising the procedure for cord blood banking, a significant loss of nucleated cells (NC) may be encountered during standard HES sedimentation protocols. This study compares four procedures for cord blood processing to obtain optimal yield of nucleated cells. Gelatin, dextran, 6% HES and 6% HES with an equal volume of phosphate-buffered saline (PBS) were compared for RBC depletion and NC recovery. Dilution of the cord blood unit with an equal volume of PBS prior to sedimentation with HES resulted in maximum NC recovery (99% [99.5 +/- 1.3%]). Although standard procedures using 6% HES are well established in Western countries, they may not be applicable in India, as a variety of factors that can affect RBC sedimentation (e.g., iron deficiency, hypoalbuminaemia, thalassaemia trait, etc.) may reduce RBC sedimentation and thus reduce NC recovery. While diluting cord blood with an equal volume of PBS is a simple method to improve the NC recovery, it does involve an additional processing step.

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

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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.

Irisin Maternal Plasma and Cord Blood Levels in Mothers with Spontaneous Preterm and Term Delivery

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Tereza Pavlova

2018-01-01

Full Text Available Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB by comparing its level between mothers with term and preterm labor. Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661. Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisin concentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (p=0.046. On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established. To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence.

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

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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.

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 we...

Loss of the ability to generate large burst-forming unit-like megakaryocytic colonies from thawed cord blood in semisolid cultures after short term suspension culture.

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Eskola, M; Bäckman, S; Möttönen, S; Kekomäki, R

2015-04-01

Total colony-forming cells from thawed cord blood units (CBUs) include megakaryocytic colony-forming units (CFU-Mks), which survive the freezing process. The aim of this study was to evaluate whether different megakaryocytic progenitors from unseparated CBUs survive the freezing process and a short-term liquid culture. Thawed samples of CBUs were cultured in liquid medium. During the cultures, serial samples were drawn to assess the growth of different megakaryocytic progenitors in a semisolid collagen medium with identical cytokines as in the liquid medium. Megakaryocytic cells were detected using immunohistochemistry and flow cytometry. In suspension culture, the megakaryocytic progenitors almost completely lost the ability to generate large (burst-forming unit-like, BFU-like) megakaryocytic colonies in semisolid cultures (large colonies, median count per chamber d0: 7.25 vs. d7: 1.5; P culture in suspension resulted in the decline of small colonies as well (d7: 16.0 vs. d14: 5.75; P = 0.0088). Total CFU-Mk count declined from 23.3 (range 12.5-34.0) at d0 to 7.25 (range 1.0-13.5) at d14 (P culture after a short suspension culture. Small CFU-Mks were observed throughout the cultures. It may be that the BFU-Mk colonies matured and acquired CFU-Mk behaviour. © 2014 International Society of Blood Transfusion.

Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

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Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

2016-01-28

Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function. © 2016 by The American Society of Hematology.

[Systematic umbilical cord blood analysis at birth: feasibility and reliability in a French labour ward].

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Ernst, D; Clerc, J; Decullier, E; Gavanier, G; Dupuis, O

2012-10-01

At birth, evaluation of neonatal well-being is crucial. It is though important to perform umbilical cord blood gas analysis, and then to analyze the samples. We wanted to establish the feasibility and reliability of systematic umbilical cord blood sampling in a French labour ward. Study of systematic umbilical cord blood gas analysis was realized retrospectively from 1000 consecutive deliveries. We first established the feasibility of the samples. Feasibility was defined by the ratio of complete cord acid-base data on the number of deliveries from alive newborns. Afterwards, we established the reliability on the remaining cord samples. Reliability was the ratio of samples that fulfilled quality criteria defined by Westgate et al. and revised by Kro et al., on the number of complete samples from alive newborns. At last, we looked for factors that would influence these results. The systematic umbilical cord blood sample feasibility reached 91.6%, and the reliability reached 80.7%. About the delivery mode, 38.6% of emergency caesarians (IC 95% [30.8-46.3]; Panalysis were significantly less validated during emergency caesarians. Realization of systematic cord blood gas analysis was followed by 8.4% of incomplete samples, and by 19.3% that were uninterpretable. Training sessions should be organized to improve the feasibility and reliability, especially during emergency caesarians. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors

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Schmidt Enrico K

2004-05-01

Full Text Available Abstract Background Erythropoietin is a multifunctional cytokine which regulates the number of erythrocytes circulating in mammalian blood. This is crucial in order to maintain an appropriate oxygen supply throughout the body. Stimulation of primary human erythroid progenitors (PEPs with erythropoietin (Epo leads to the activation of the mitogenic kinases (MEKs and Erks. How this is accomplished mechanistically remained unclear. Results Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors. Conclusions These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.

Evaluation of CF/CM, concentration ratios for elements in fetus to mother, using cord blood and maternal blood

International Nuclear Information System (INIS)

Watanabe, Y.; Yukawa, M.; Kim, H.S.; Nishimura, Y.; Osada, H.; Sekiya, S.

2000-01-01

ICRP recommends age-dependent dose evaluation for intakes of radionuclides by inhalation and ingestion, and gave age-specific biokinetic models and dose coefficients (doses per unit intake) for infants, children and adults in the publications. Dose coefficients are also needed for the assessment of exposures received in utero and after birth by the offspring of the woman who has received intakes of radionuclides. In the model that has been adopted by ICRP, the doses to the developing fetus are calculated using CF/CM values, concentration ratios for radionuclides in the fetus and the maternal tissues. The purpose of this study is to evaluate the CF/CM of each radionuclide by the measurement of element concentration in cord blood and maternal blood. Blood samples were obtained from 35 mothers who delivered in Department of Obstetrics and Gynecology of Chiba University. Just after the delivery, unbiblical cord blood was sampled. Maternal blood was also obtained from the arm vein within 30 minutes after the delivery. The serum was separated from the blood sample with centrifugation. About 50 mg of freezer-dried whole blood and serum were digested with 0.5 ml of 65% ultra-pure nitric acid and 0.2 ml of 30% hydrogen peroxide in a microwave digester. The diluted solutions were used for the determination of elements by ICP-MS (Inductively Coupled Plasma Mass Spectrometry) and ICP-AES (Inductively Coupled Plasma Atomic Emission Spectrometry). The elements determined in these samples included Mg, K, Ca, Mn, Fe, Cu, Zn, Se, Rb, Sr and Cs. The concentration of Cu was higher in the maternal blood than in the cord blood in both whole blood and serum. On the other hand, Mn and Fe were higher in the cord blood. The differences of concentration ratios among elements and the differences among tissues will be discussed. (author)

Efficient derivation of multipotent neural stem/progenitor cells from non-human primate embryonic stem cells.

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Hiroko Shimada

Full Text Available The common marmoset (Callithrix jacchus is a small New World primate that has been used as a non-human primate model for various biomedical studies. We previously demonstrated that transplantation of neural stem/progenitor cells (NS/PCs derived from mouse and human embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs promote functional locomotor recovery of mouse spinal cord injury models. However, for the clinical application of such a therapeutic approach, we need to evaluate the efficacy and safety of pluripotent stem cell-derived NS/PCs not only by xenotransplantation, but also allotransplantation using non-human primate models to assess immunological rejection and tumorigenicity. In the present study, we established a culture method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs. Marmoset ESC-derived neurospheres could be passaged repeatedly and showed sequential generation of neurons and astrocytes, similar to that of mouse ESC-derived NS/PCs, and gave rise to functional neurons as indicated by calcium imaging. Although marmoset ESC-derived NS/PCs could not differentiate into oligodendrocytes under default culture conditions, these cells could abundantly generate oligodendrocytes by incorporating additional signals that recapitulate in vivo neural development. Moreover, principal component analysis of microarray data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene expression profiles to those of fetal brain-derived NS/PCs by repeated passaging. Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate evaluation by allotransplantation of NS/PCs into non-human primate models, but are also applicable to analysis of iPSCs established from transgenic disease model marmosets.

Benzophenone-type UV filters in urine and blood from children, adults, and pregnant women in China: Partitioning between blood and urine as well as maternal and fetal cord blood

International Nuclear Information System (INIS)

Zhang, Tao; Sun, Hongwen; Qin, Xiaolei; Wu, Qian; Zhang, Yanfeng; Ma, Jing; Kannan, Kurunthachalam

2013-01-01

Limited information exists on the exposure of benzophenone (BP)-type UV filters (i.e., sunscreen compounds) in children, adults, and pregnant women in China. In this study, we determined the concentrations of five BP derivatives, BP-1, BP-2, BP-3, BP-8, and 4OH-BP in urine (n = 101) as well as paired specimens of blood and urine (n = 24 pairs) collected from adults; in matched maternal and fetal cord blood (n = 20 pairs) collected from pregnant women; and in blood collected from children (n = 10). 4OH-BP, BP-1, and BP-3 were found in 61%, 57%, and 25%, respectively, of the urine samples analyzed. 4OH-BP was found in all blood samples; BP-3 was found more frequently in the blood of adults (83%), followed, in decreasing order, by pregnant women (35%) and children (30%). Among all adults, urinary BP-3 concentrations were significantly (p < 0.001) positively correlated with urinary BP-1 concentrations. Nevertheless, no significant correlations were found between urinary concentrations of BP-3 (or BP-1) and 4OH-BP. Our results suggest that human exposure to BP-3 and BP-1 is related, whereas 4OH-BP originates from a discrete source. Females had higher urinary concentrations of BP-3, BP-1 and 4OH-BP than males. The distribution profiles of BP-1 and its parent compound (i.e., BP-3) in urine decreased with increasing age of donors (p < 0.05). The ratio of concentrations of BP-3 between blood and urine was 0.21 in adults, which was significantly lower than that for 4OH-BP (0.36). The concentration ratio of BPs between cord blood and maternal blood was higher for 4OH-BP (0.61) than that for BP-3 (0.48), which suggested greater trans-placental transfer potential of 4OH-BP. This is the first study to document the occurrence of BPs in paired urine and blood, and in matched maternal and fetal cord blood. Highlights: • Benzophenone (BP) concentrations are determined in paired blood and urine for the first time. • BP-3 and 4OH-BP partition preferentially into urine. • Cord to

Benzophenone-type UV filters in urine and blood from children, adults, and pregnant women in China: Partitioning between blood and urine as well as maternal and fetal cord blood

Energy Technology Data Exchange (ETDEWEB)

Zhang, Tao; Sun, Hongwen; Qin, Xiaolei [College of Environmental Sciences and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin 300071 (China); Wu, Qian [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Albany, NY 12201 (United States); Zhang, Yanfeng [College of Environmental Sciences and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin 300071 (China); Ma, Jing [Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, 99 Shangda Road, P.O. Box 144, Shanghai 200444 (China); Kannan, Kurunthachalam, E-mail: kkannan@wadsworth.org [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Albany, NY 12201 (United States); International Joint Research Center for Persistent Toxic Substances, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090 (China)

2013-09-01

Limited information exists on the exposure of benzophenone (BP)-type UV filters (i.e., sunscreen compounds) in children, adults, and pregnant women in China. In this study, we determined the concentrations of five BP derivatives, BP-1, BP-2, BP-3, BP-8, and 4OH-BP in urine (n = 101) as well as paired specimens of blood and urine (n = 24 pairs) collected from adults; in matched maternal and fetal cord blood (n = 20 pairs) collected from pregnant women; and in blood collected from children (n = 10). 4OH-BP, BP-1, and BP-3 were found in 61%, 57%, and 25%, respectively, of the urine samples analyzed. 4OH-BP was found in all blood samples; BP-3 was found more frequently in the blood of adults (83%), followed, in decreasing order, by pregnant women (35%) and children (30%). Among all adults, urinary BP-3 concentrations were significantly (p < 0.001) positively correlated with urinary BP-1 concentrations. Nevertheless, no significant correlations were found between urinary concentrations of BP-3 (or BP-1) and 4OH-BP. Our results suggest that human exposure to BP-3 and BP-1 is related, whereas 4OH-BP originates from a discrete source. Females had higher urinary concentrations of BP-3, BP-1 and 4OH-BP than males. The distribution profiles of BP-1 and its parent compound (i.e., BP-3) in urine decreased with increasing age of donors (p < 0.05). The ratio of concentrations of BP-3 between blood and urine was 0.21 in adults, which was significantly lower than that for 4OH-BP (0.36). The concentration ratio of BPs between cord blood and maternal blood was higher for 4OH-BP (0.61) than that for BP-3 (0.48), which suggested greater trans-placental transfer potential of 4OH-BP. This is the first study to document the occurrence of BPs in paired urine and blood, and in matched maternal and fetal cord blood. Highlights: • Benzophenone (BP) concentrations are determined in paired blood and urine for the first time. • BP-3 and 4OH-BP partition preferentially into urine. • Cord to

Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates

International Nuclear Information System (INIS)

Iranpour, R.; Besharati, Amir A.; Nasseri, F.; Hashemipour, M.; Kelishadi, R.; Balali-Mood, M.

2007-01-01

Objective was to compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. From April 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in the 32 mother-infant pairs with IUGR full term neonates and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47+- 16.75 versus 113.08+-19.08 ug/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56+-19.71 versus 135.26+-26.91 ug/L, p=0.07). Maternal lead levels were strongly related with related with cord blood in both IUGR and normal groups (r=0.8, p 100ug/L by the centers for disease control; however, this was not statistically different between the groups. Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area. (author)

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.

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

Hexachlorocyclohexanes (HCHs) in placenta and umbilical cord blood and dietary intake for women in Beijing, China

International Nuclear Information System (INIS)

Yu, Yanxin; Wang, Bin; Wang, Xilong; Wang, Rong; Wang, Wentao; Shen, Guofeng; Shen, Huizhong; Li, Wei; Wong, Minghong; Liu, Wenxin; Tao, Shu

2013-01-01

Placenta and umbilical cord blood are important media for investigating maternal–fetal exposure to environmental pollutants. Historically hexachlorocyclohexanes (HCHs) were once widely-used in China. In this study, residues of HCHs were measured in placenta and umbilical cord blood samples for 40 women from Beijing. The measured median values of HCHs were 62.0 and 68.8 ng/g fat in placenta and umbilical cord blood, respectively. Concentrations of HCHs in placenta and umbilical cord blood of urban cohort were higher than those of rural group due to enhanced consumption of fish, meat, and milk. Residues of HCHs in placenta were significantly correlated with total food consumption, dietary intake, and maternal age, and could be predicted using the parameters dependent upon ingestion of meat and milk. The transplacental exposure of fetuses to HCHs was revealed by a close association between the residual levels in the paired placenta and the paired umbilical cord blood samples. -- Highlights: •Medians of HCH in placenta and umbilical cord blood of 40 puerperal women from Beijing were 62.0 and 68.8 ng/g⋅fat. •HCHs in placenta and umbilical cord blood of urban cohort were higher than those of rural one. •HCH residues in placenta were significantly correlated with total food consumption, daily dietary intake, and maternal age. •The transplacental exposure of fetus to HCHs was revealed. -- HCHs in placenta of women in Beijing were significantly correlated with total food consumption, dietary intake, and maternal age

Cord Blood Leptin Levels in Gestational Diabetes

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Özlem Şengül

2010-08-01

CONCLUSION: In this study there is a minimal clinical effect of cord blood leptin on macrosomia in women with GD, although it is increased in GD and associated with birthweight. Therefore overgrowth may be a result of direct anabolic effect of insulin, rather than indirect effect via leptin.

Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

Energy Technology Data Exchange (ETDEWEB)

Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

2014-03-18

SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

Directory of Open Access Journals (Sweden)

Z.H. Wang

2014-04-01

Full Text Available SRY-related high-mobility-group box 9 (Sox9 gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs. After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

International Nuclear Information System (INIS)

Wang, Z.H.; Li, X.L.; He, X.J.; Wu, B.J.; Xu, M.; Chang, H.M.; Zhang, X.H.; Xing, Z.; Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y.

2014-01-01

SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering

Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

International Nuclear Information System (INIS)

Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

1987-01-01

The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

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

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......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...

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes.

Science.gov (United States)

Li, Xingfu; Duan, Li; Liang, Yujie; Zhu, Weimin; Xiong, Jianyi; Wang, Daping

2016-01-01

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs) and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2) and decreased type I collagen (COL1) protein expression levels. SRY-box 9 (SOX9) mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

Science.gov (United States)

Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

2015-08-01

The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

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

[Freezing umbilical-cord blood and bone marrow for one's own use: present-day quackery?

NARCIS (Netherlands)

Braat, D.D.M.; Mummery, C.L.; Schattenberg, A.V.M.B.; Borst-Eilers, E.

2006-01-01

In the Netherlands, the practice of private freezing and banking of umbilical-cord blood is increasing. In a questionnaire, Dutch midwives and gynaecologists were asked about their attitude towards cord-blood collection if asked to perform this after delivery. The response rate was 35% (125/356) and

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

Science.gov (United States)

Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

2014-03-01

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

Reference Values for Umbilical Cord Blood Gases of Newborns Delivered by Elective Cesarean Section.

Science.gov (United States)

Manomayangkul, Kattiya; Siriussawakul, Arunotai; Nimmannit, Akarin; Yuyen, Thassayu; Ngerncham, Sopapan; Reesukumal, Kanit

2016-05-01

Umbilical cord blood gas values are better indicators of perinatal asphyxia than Apgar scores. Many studies have reported normal ranges of umbilical cord blood gases, which vary greatly due to many factors. This study aimed to establish the reference values of umbilical cord blood gases of normal cesarean newborns in a university hospital setting. Blood samples from the umbilical artery and vein were collected from 160 newborns delivered by elective cesarean section. The indications for caesarean section were not due to fetal distress, intrauterine growth retardation, or non-reassuring fetal heart rate. The blood samples were collected immediately after birth in the operating room and then sent for blood-gas analysis. The blood-gas values were statistically analyzed and reported. The cord blood collected from 160 newborns was analyzed in this study. Seventy-eight percent (115) of the parturients were hypotensive before delivery. All Apgar scores at one and five minutes after delivery were at least 7. The calculated reference range of the umbilical arterial pH was 7.18-7.42, of pO₂was 6.43-29.43 mmHg, of pCO₂was 33.44-66.56 mmHg, and of HCO₃was 15.60-30.70 mEq/L. The reference range obtained for the umbilical venous pH was 7.28-7.44,for pO₂was 13.97-37.13 mmHg, for pCO₂was 30.70-57.0 mmHg, and for HCO₃was 18.50-29.90 mEq/L. The study determined normal reference values as a result of umbilical cord blood gas analyses.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

Energy Technology Data Exchange (ETDEWEB)

Shafiee, Abbas [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD (Australia); Seyedjafari, Ehsan [Department of Biotechnology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Sadat Taherzadeh, Elham [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Dinarvand, Peyman [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); The Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO (United States); Soleimani, Masoud [Hematology Department, Faculty of Medical Science, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: jafar_ai@tums.ac.ir [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2014-07-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

International Nuclear Information System (INIS)

Shafiee, Abbas; Seyedjafari, Ehsan; Sadat Taherzadeh, Elham; Dinarvand, Peyman; Soleimani, Masoud; Ai, Jafar

2014-01-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers

Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

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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.

Knowledge and attitudes of pregnant women with regard to collection, testing and banking of cord blood stem cells.

Science.gov (United States)

Fernandez, Conrad V; Gordon, Kevin; Van den Hof, Michiel; Taweel, Shaureen; Baylis, Françoise

2003-03-18

Umbilical cord blood is used as a source of hematopoietic stem cells for bone marrow transplantation in the treatment of malignant and nonmalignant disease. We sought to examine pregnant women's knowledge and attitudes regarding cord blood banking, as their support is crucial to the success of cord blood transplant programs. A questionnaire examining sociodemographic factors and women's attitudes to cord blood banking was developed on the basis of findings from 2 focus groups and a pilot study. The questionnaire was distributed to 650 women attending antenatal clinics at a regional women's hospital between April and July 2001. A total of 443 women (68%) responded. More than half of the women (307/438 or 70% [95% confidence interval, CI, 66% to 74%]) reported poor or very poor knowledge about cord blood banking. Many of the respondents (299/441 or 68% [95% CI 63% to 72%]) thought that physicians should talk to pregnant women about the collection of cord blood, and they wanted to receive information about this topic from health care professionals (290/441 or 66% [95% CI 61% to 70%]) or prenatal classes (308/441 or 70% [95% CI 65% to 74%]). Most of the women (379/442 or 86% [95% CI 82% to 89%]) would elect to store cord blood in a public bank, many citing altruism as the reason for this choice. A much smaller proportion (63/442 or 14% [95% CI 11% to 18%]) would elect private banking, indicating that this would be a good investment or that they would feel guilty if the blood had not been stored. Additional acceptable uses for cord blood included research (mentioned by 294/436 women or 67% [95% CI 63% to 72%]) and gene therapy (mentioned by 169/437 women or 39% [95% CI 34% to 43%]). Most of the women in this study supported the donation of cord blood to public cord blood banks for potential transplantation and research.

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...

Awareness of cord blood collection and the impact on banking.

Science.gov (United States)

Bhandari, Rusha; Lindley, Amy; Bhatla, Deepika; Babic, Aleksandar; Mueckl, Kathy; Rao, Rakesh; Brooks, Paula; Geiler, Vicki; Gross, Gilad; Al-Hosni, Mohamad; Shenoy, Shalini

2017-07-01

Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation especially in minority populations with limited chances of finding a histocompatible volunteer donor in the registry. UCB has the advantages of early availability, successful outcomes despite some histocompatibility mismatch, and low incidence of chronic graft-versus-host disease. Public cord blood banks that disseminate UCB products for transplant depend on voluntary donation at participating hospitals and obstetrical providers for collection. Using survey questionnaires, we evaluated attitudes toward UCB donation, the frequency of donation, and provider opinions on UCB collection in the greater St. Louis metropolitan area that caters to minority ethnicities in significant numbers. Our data suggest that nervousness and lack of information regarding the donation and utility of the product were ubiquitous reasons for not donating. Additionally, irrespective of age or level of education, women relied on healthcare providers for information regarding UCB donation. Providers reported primarily time constraints to discussing UCB donation at prenatal visits (54%). Of the interviewees, 62% donated UCB. Fallout due to refusal or preferring private banking was miniscule. These results suggest that dedicated personnel focused on disseminating information, obtaining consent, and collecting the UCB product at major hospitals can enrich cord blood banks especially with minority cords. Sustained and focused efforts could improve upon a relatively high wastage rate and ensure a robust supply of UCB products at local public banks. © 2017 Wiley Periodicals, Inc.

Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

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Chen C

2016-04-01

Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

Umbilical Cord Blood Banking for Transplantation in Morocco: Problems and opportunities

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Mazini L

2014-11-01

Full Text Available Since the success of the first umbilical cord blood (UCB transplantation in a child with Fanconi anaemia in 1989, great interests have emerged for this source of stem cells. UCB provides an unlimited source of ethnically diverse stem cells and is an alternative for bone marrow (BM and peripheral blood (PB heamatopoietic stem cell transplantation (HSCT. Thus, UCB and manipulated stem cells are now collected and banked according to international accreditation standards for listing on registries allowing rapid search and accessibility worldwide. This work aims to identify problems limiting the creation of a Moroccan cord blood bank and to highlight opportunities and issues of a new legislation promoting additional applications of cell therapy.

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

International Nuclear Information System (INIS)

Fagerstedt, Sara; Kippler, Maria; Scheynius, Annika; Gutzeit, Cindy; Mie, Axel; Alm, Johan; Vahter, Marie

2015-01-01

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

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

Stromal Cells Act as Guardians for Endothelial Progenitors by Reducing Their Immunogenicity After Co-Transplantation.

Science.gov (United States)

Souidi, Naima; Stolk, Meaghan; Rudeck, Juliane; Strunk, Dirk; Schallmoser, Katharina; Volk, Hans-Dieter; Seifert, Martina

2017-05-01

Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal stem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo. Immunodeficient mice received subcutaneous grafts containing human ECFCs alone, or pairs of human ECFCs/MSCs from the same umbilical cord (UC) to study vasculogenesis in the presence of human leukocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNγ) stimulation during ECFC/MSC coculture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNγ-induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in cocultures. ECFC-induced T cell proliferation was abolished after MSC coculture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase activation. Additionally, allospecific CD8 + T cell-mediated lysis of ECFCs was reduced in cocultures. ECFC/MSC coapplication in immunodeficient mice not only promoted the generation of improved blood vessel architecture after 6 weeks, but also reduced intragraft immune cell infiltration and endothelial HLA-DR expression following PBMC reconstitution. Crosstalk between UC-derived ECFCs and MSCs after combined transplantation can lower the risk of ECFC rejection, thus enabling their coapplication for therapeutic vasculogenesis. Stem Cells 2017;35:1233-1245. © 2017 AlphaMed Press.

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

on Asthma in Childhood (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS), asthma, respiratory infections, allergic rhinitis, and eczema, at age 0-7 yrs were diagnosed exclusively by the COPSAC pediatricians strictly adhering to predefined algorithms. Objective assessments of lung......BACKGROUND: Epidemiological studies have suggested an association between maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy in the offspring. However, prospective clinical studies on vitamin D measured in cord blood and development of clinical end-points are sparse....... OBJECTIVE: To investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin D) level and investigator-diagnosed asthma- and allergy-related conditions during preschool-age. METHODS: Cord blood 25(OH)-Vitamin D level was measured in 257 children from the Copenhagen Prospective Studies...

Manufacture of endothelial colony-forming progenitor cells from steady-state peripheral blood leukapheresis using pooled human platelet lysate.

Science.gov (United States)

Siegel, Georg; Fleck, Erika; Elser, Stefanie; Hermanutz-Klein, Ursula; Waidmann, Marc; Northoff, Hinnak; Seifried, Erhard; Schäfer, Richard

2018-05-01

Endothelial colony-forming progenitor cells (ECFCs) are promising candidates for cell therapies. However, ECFC translation to the clinic requires optimized isolation and manufacture technologies according to good manufacturing practice (GMP). ECFCs were manufactured from steady-state peripheral blood (PB) leukapheresis (11 donors), using GMP-compliant technologies including pooled human platelet (PLT) lysate, and compared to human umbilical cord endothelial cells, human aortic endothelial cells, and human cerebral microvascular endothelial cells. Specific variables assessed were growth kinetics, phenotype, trophic factors production, stimulation of tube formation, and Dil-AcLDL uptake. ECFCs could be isolated from PB leukapheresis units with mean processed volume of 5411 mL and mean white blood cell (WBC) concentration factor of 8.74. The mean frequency was 1.44 × 10 -8 ECFCs per WBC, corresponding to a mean of 177.8 ECFCs per apheresis unit. Expandable for up to 12 cumulative population doublings, calculated projection showed that approximately 730 × 10 3 ECFCs could be manufactured from 1 apheresis unit. ECFCs produced epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor (VEGF)-A, PLT-derived growth factor-B, interleukin-8, and monocyte chemoattractant protein-1, featured high potential for capillary-like tubes formation, and showed no telomerase activity. They were characterized by CD29, CD31, CD44, CD105, CD117, CD133, CD144, CD146, and VEGF-R2 expression, with the most common subpopulation CD34+CD117-CD133-. Compared to controls, ECFCs featured greater Dil-AcLDL uptake and higher expression of CD29, CD31, CD34, CD44, CD144, and VEGF-R2. Here we show that isolation of ECFCs with proangiogenic profile from steady-state PB leukapheresis is feasible, marking a first step toward ECFC product manufacture according to GMP. © 2018 AABB.

Proportional-Integral-Derivative (PID) Control of Secreted Factors for Blood Stem Cell Culture.

Science.gov (United States)

Caldwell, Julia; Wang, Weijia; Zandstra, Peter W

2015-01-01

Clinical use of umbilical cord blood has typically been limited by the need to expand hematopoietic stem and progenitor cells (HSPC) ex vivo. This expansion is challenging due to the accumulation of secreted signaling factors in the culture that have a negative regulatory effect on HSPC output. Strategies for global regulation of these factors through dilution have been developed, but do not accommodate the dynamic nature or inherent variability of hematopoietic cell culture. We have developed a mathematical model to simulate the impact of feedback control on in vitro hematopoiesis, and used it to design a proportional-integral-derivative (PID) control algorithm. This algorithm was implemented with a fed-batch bioreactor to regulate the concentrations of secreted factors. Controlling the concentration of a key target factor, TGF-β1, through dilution limited the negative effect it had on HSPCs, and allowed global control of other similarly-produced inhibitory endogenous factors. The PID control algorithm effectively maintained the target soluble factor at the target concentration. We show that feedback controlled dilution is predicted to be a more cost effective dilution strategy compared to other open-loop strategies, and can enhance HSPC expansion in short term culture. This study demonstrates the utility of secreted factor process control strategies to optimize stem cell culture systems, and motivates the development of multi-analyte protein sensors to automate the manufacturing of cell therapies.

Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model

OpenAIRE

Yousefifard, Mahmoud; Nasirinezhad, Farinaz; Shardi Manaheji, Homa; Janzadeh, Atousa; Hosseini, Mostafa; Keshavarz, Mansoor

2016-01-01

Background Stem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief. Methods A compression model was used to induce SCI in a rat model. A w...

Microbial load of umbilical cord blood Ureaplasma species and Mycoplasma hominis in preterm prelabor rupture of membranes.

Science.gov (United States)

Kacerovsky, Marian; Pliskova, Lenka; Menon, Ramkumar; Kutova, Radka; Musilova, Ivana; Maly, Jan; Andrys, Ctirad

2014-11-01

To evaluate Ureaplasma species and M. hominis DNA in the umbilical cord blood and its correlation with its microbial load in the amniotic fluid, as a measure of microbial burden in fetal inflammatory response and neonatal outcome in pregnancies complicated by preterm prelabor rupture of membranes (pPROM). A retrospective study of 158 women with singleton pregnancies complicated by pPROM between 24(0/7) and 36(6/7) weeks was conducted. Amniotic fluid was obtained from all women by transabdominal amniocentesis, and umbilical cord blood was obtained by venipuncture from umbilical cords immediately after the delivery of the neonates. The Ureaplasma species and M. hominis DNA was quantitated using absolute quantification techniques. Ureaplasma species and M. hominis DNA was identified in 9% of the umbilical cord blood samples. No correlation between the amniotic fluid and umbilical cord blood microbial load was observed. The presence of Ureaplasma species and M. hominis DNA in the umbilical cord blood had no impact on short-term neonatal morbidity. A high microbial load of genital mycoplasma Ureaplasma species DNA in the umbilical cord in pregnancies complicated by pPROM is not associated with a high fetal inflammatory response and is therefore not associated with serious neonatal morbidity.

[Influence of cattle cord blood fraction below 5 kD on biochemical parameters of blood in experimental chronic stomach ulcer in rats].

Science.gov (United States)

Gulevskiĭ, A K; Abakumova, E S; Moiseeva, N N; Dolgikh, O L

2008-01-01

Influence of cattle cord blood fraction (below 5 kD) on lipid peroxidation product content and alkaline phosphatase activity-in peripheral blood was studied on the experimental subchronic stomach ulcer model in rats. It has been shown that the fraction administrations normalize thiobarbituric-active product content and alkaline phosphatase activity in blood, which testifies to decreasing inflammatory reaction in the mucous membrane of the stomach. The fraction administrations accelerate the processes of regeneration of the mucous membrane of the stomach up to complete healing of ulcer defects. Cord blood fraction below 5 kD from cattle possesses antiulcer activity which is analogous to the actovegin activity. It has been shown by gel-penetrating chromatography that the pattern of cord blood fraction low molecular substances is different from the actovegin pattern both qualitatively and quantitatively.

Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS.

Directory of Open Access Journals (Sweden)

Svitlana Garbuzova-Davis

2007-11-01

Full Text Available The blood-brain barrier (BBB, blood-spinal cord barrier (BSCB, and blood-cerebrospinal fluid barrier (BCSFB control cerebral/spinal cord homeostasis by selective transport of molecules and cells from the systemic compartment. In the spinal cord and brain of both ALS patients and animal models, infiltration of T-cell lymphocytes, monocyte-derived macrophages and dendritic cells, and IgG deposits have been observed that may have a critical role in motor neuron damage. Additionally, increased levels of albumin and IgG have been found in the cerebrospinal fluid in ALS patients. These findings suggest altered barrier permeability in ALS. Recently, we showed disruption of the BBB and BSCB in areas of motor neuron degeneration in the brain and spinal cord in G93A SOD1 mice modeling ALS at both early and late stages of disease using electron microscopy. Examination of capillary ultrastructure revealed endothelial cell degeneration, which, along with astrocyte alteration, compromised the BBB and BSCB. However, the effect of these alterations upon barrier function in ALS is still unclear. The aim of this study was to determine the functional competence of the BSCB in G93A mice at different stages of disease.Evans Blue (EB dye was intravenously injected into ALS mice at early or late stage disease. Vascular leakage and the condition of basement membranes, endothelial cells, and astrocytes were investigated in cervical and lumbar spinal cords using immunohistochemistry. Results showed EB leakage in spinal cord microvessels from all G93A mice, indicating dysfunction in endothelia and basement membranes and confirming our previous ultrastructural findings on BSCB disruption. Additionally, downregulation of Glut-1 and CD146 expressions in the endothelial cells of the BSCB were found which may relate to vascular leakage.Results suggest that the BSCB is compromised in areas of motor neuron degeneration in ALS mice at both early and late stages of the disease.

Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

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Nicoletta Iacovidou

2008-01-01

Full Text Available Ischemia-modified albumin (IMA is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’. Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035, and offspring of multigravidas (P = .021. In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes

Directory of Open Access Journals (Sweden)

Xingfu Li

2016-01-01

Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2 and decreased type I collagen (COL1 protein expression levels. SRY-box 9 (SOX9 mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

Predicting onset of chronic lung disease using cord blood cytokines.

Science.gov (United States)

Takao, Daishi; Ibara, Satoshi; Tokuhisa, Takuya; Ishihara, Chie; Maede, Yoshinobu; Matsui, Takako; Tokumasu, Hironobu; Sato, Kyoko; Hirakawa, Eiji; Kabayama, Chika; Yamamoto, Masakatu

2014-08-01

Applicability of cord blood interleukin-6 (IL-6) and interleukin-8 (IL-8) as markers for early prediction of the onset of chronic lung disease (CLD) due to intrauterine infection was investigated in the present study. Eighty very low-birthweight infants with chorioamnionitis were divided into two groups: the CLD group (42 patients) and the non-CLD group (38 patients), according to the presence or absence of CLD, and the clinical background and cord blood IL-6 and IL-8 levels in each group were compared and investigated. The CLD group had significantly longer duration of mechanical ventilation and hospitalization (P CLD group. Using the receiver operating characteristic curves of CLD onset for both IL-6 and IL-8, the cut-off value of IL-6 for predicting onset of CLD was 48.0 pg/mL, and its sensitivity and specificity were 76% and 96%, respectively. The cut-off value for IL-8 was 66.0 pg/mL, and its sensitivity and specificity were 71% and 82%, respectively. The cord blood levels of both IL-6 and IL-8 were significantly higher in the CLD group, indicating that both IL-6 and IL-8 are useful predictors of onset of CLD. © 2014 Japan Pediatric Society.

Cord Blood Stem Cell Procurement in Minority Donors

National Research Council Canada - National Science Library

Ratanatharathorn, Voravit

2008-01-01

... of building minority CBU inventory. This final annual report is to give the report of the transplantation outcomes of African/American CBU recipients compared with other racial groups. This analysis is limited to those patients who have received an allogeneic cord blood stem cell transplantation at Karmanos Cancer Center.

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

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Sandeep Gupta

2018-02-01

Full Text Available Summary: Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC- or induced pluripotent stem cell (hiPSC-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs, which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients. : In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol. Keywords: spinal cord, neurons, sensory interneurons, proprioception, mechanosensation, human embryonic stem cells, induced pluripotent stem cells, directed differentiation, primate spinal cord, mouse spinal cord

Improving engraftment and immune reconstitution in umbilical cord blood transplantation

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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.

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

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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.

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

Science.gov (United States)

Rahbar, Mohammad H.; Samms-Vaughan, Maureen; Dickerson, Aisha S.; Hessabi, Manouchehr; Bressler, Jan; Coore Desai, Charlene; Shakespeare-Pellington, Sydonnie; Reece, Jody-Ann; Morgan, Renee; Loveland, Katherine A.; Grove, Megan L.; Boerwinkle, Eric

2015-01-01

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. PMID:25915835

Short-term effects of early-acting and multilineage hematopoietic growth factors on the repair and proliferation of irradiated pure cord blood (CB) CD34 hematopoietic progenitor cells

International Nuclear Information System (INIS)

Ziegler, Benedikt L.; Sandor, Peter S.; Plappert, Ulla; Thoma, Stefan; Mueller, Robert; Bock, Thomas; Thomas, Christian A.; Nothdurft, Wilhelm; Fliedner, Theodor M.

1998-01-01

Purpose: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro or in vivo on the survival of hematopoietic stem and progenitor cells after accidental or therapeutic total body irradiation. Methods and Materials: We studied the clonogenic survival and DNA repair of irradiated (0.36, 0.73, and 1.46 Gy) CD34 + cord blood (CB) cells after short-term incubation (24 h) with GFs. CD34 + cells were stimulated with basic fibroblast growth factor (bFGF), stem cell factor/c-kit ligand (SCF), interleukin-3 (IL-3), IL-6, leukemia inhibitory factor (LIF), and granulocyte-monocyte colony stimulating factor (GM-CSF) alone or in combination in short-term serum-free liquid suspension cultures (LSC) immediately after irradiation and then assayed for clonogenic progenitors. DNA repair was evaluated by analysis of DNA strand breaks using the comet assay. Survival of CFU-GM, BFU-E, and CFU-Mix was determined and dose-response curves were fitted to the data. Results: The radiobiological parameters (D 0 and n) showed significant GF(s) effects. Combination of IL-3 with IL-6, SCF or GM-CSF resulted in best survival for CFU-GM BFU-E and CFU-Mix, respectively. Combinations of three or more GFs did not increase the survival of clonogenic CD34 + cells compared to optimal two-factor combinations. The D 0 values for CFU-GM, BFU-E, and CFU-Mix ranged between 0.56-1.15, 0.41-2.24, and 0.56-1.29 Gy, respectively. As for controls, the curves remained strictly exponential, i.e., all survival curves were strictly exponential without any shoulder (extrapolation numbers n = 1 for all tested GF(s). DNA repair capacity of CD34 + cells determined by comet assay, was measured before, immediately after irradiation, as well as 30 and 120 min after irradiation at 1 Gy. Notably, after irradiation the 2-h repair of cytokine-stimulated and unstimulated CD34 + cells was similar. Conclusion: Our data indicate that increased survival of irradiated CB CD34 + cells after short-term GF treatment is

Screening for glucose-6-phosphate dehydrogenase deficiency in neonates: a comparison between cord and peripheral blood samples.

Science.gov (United States)

AlSaif, Saif; Ponferrada, Ma Bella; AlKhairy, Khalid; AlTawil, Khalil; Sallam, Adel; Ahmed, Ibrahim; Khawaji, Mohammed; AlHathlol, Khalid; Baylon, Beverly; AlSuhaibani, Ahmed; AlBalwi, Mohammed

2017-07-11

The use of cord blood in the neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is being done with increasing frequency but has yet to be adequately evaluated against the use of peripheral blood sample which is usually employed for confirmation. We sought to determine the incidence and gender distribution of G6PD deficiency, and compare the results of cord against peripheral blood in identifying G6PD DEFICIENCY neonates using quantitative enzyme activity assay. We carried out a retrospective and cross-sectional study employing review of primary hospital data of neonates born in a tertiary care center from January to December 2008. Among the 8139 neonates with cord blood G6PD assays, an overall incidence of 2% for G6PD deficiency was computed. 79% of these were males and 21% were females with significantly more deficient males (p blood samples (n = 1253) showed a significantly higher mean G6PD value for peripheral than cord blood (15.12 ± 4.52 U/g and 14.52 ± 4.43 U/g, respectively, p = 0.0008). However, the proportion of G6PD deficient neonates did not significantly differ in the two groups (p = 0.79). Sensitivity of cord blood in screening for G6PD deficiency, using peripheral G6PD assay as a gold standard was 98.6% with a NPV of 99.5%. There was no difference between cord and peripheral blood samples in discriminating between G6PD deficient and non-deficient neonates. A significantly higher mean peripheral G6PD assay reinforces the use of cord blood for neonatal screening since it has substantially low false negative results.

DNA Methylation Patterns in Cord Blood of Neonates Across Gestational Age: Association With Cell-Type Proportions.

Science.gov (United States)

Braid, Susan M; Okrah, Kwame; Shetty, Amol; Corrada Bravo, Hector

A statistical methodology is available to estimate the proportion of cell types (cellular heterogeneity) in adult whole blood specimens used in epigenome-wide association studies (EWAS). However, there is no methodology to estimate the proportion of cell types in umbilical cord blood (also a heterogeneous tissue) used in EWAS. The objectives of this study were to determine whether differences in DNA methylation (DNAm) patterns in umbilical cord blood are the result of blood cell type proportion changes that typically occur across gestational age and to demonstrate the effect of cell type proportion confounding by comparing preterm infants exposed and not exposed to antenatal steroids. We obtained DNAm profiles of cord blood using the Illumina HumanMethylation27k BeadChip array for 385 neonates from the Boston Birth Cohort. We estimated cell type proportions for six cell types using the deconvolution method developed by . The cell type proportion estimates segregated into two groups that were significantly different by gestational age, indicating that gestational age was associated with cell type proportion. Among infants exposed to antenatal steroids, the number of differentially methylated CpGs dropped from 127 to 1 after controlling for cell type proportion. EWAS utilizing cord blood are confounded by cell type proportion. Careful study design including correction for cell type proportion and interpretation of results of EWAS using cord blood are critical.

Study of Engraftment of human cord blood cells to rescue the sublethal radiation damage mice

International Nuclear Information System (INIS)

Cao Xiangshan; Zou Zhenghui; Yu Fei; Zhang Zhilin; Lin Baojue

1997-01-01

To investigate alternative source of hematopoiesis stem cells to rescue the sublethal radiation damage (SRD) casualties. Human-umbilical cord blood hematopoietic cells were transplanted into SRD mice, the survival rate and the hematopoiesis reconstitution of bone marrow were assessed. The survival rate, in the mice transplanted and the untransplanted, were 90% and 10% respectively. Bone marrow and spleen of survival mice showed human leukocytic antigen CD45 + cells. Presence of multilineage engraftment, including myeloid and erythroid lineages, were found indicating that immature human cells home to the mouse bone marrow. conclusion: engraftment of umbilical cord blood cells is very useful to reconstitute hematopoiesis of SRD casualties. As cord blood has many advantages over bone marrow and peripheral blood, it is important in rescuing radiation accidental casualties

Levels of micronutrients and heavy metals in cord blood and ...

African Journals Online (AJOL)

The basis of the impact of HAP on maternal and fetal health was assessed by determining the levels of teratogenic heavy metals [Lead (Pb), Mercury (Hg)] and micronutrients associated with DNA methylation [Zinc (Zn), Iodine (I), vitamins B6 and B12, folic acid and homocysteine] in cord blood of babies and maternal blood ...

Screening of Glucose-6-Phosphate Dehydrogenase Deficiency in Cord Blood

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Can Acipayam

2014-02-01

Aim: Glucose-6-phosphate dehydrogenase deficiency is an important factor in etiology of pathologic neonatal jaundice. The aim of this study was to indicate the significance of screening glucose-6-phosphate dehydrogenase deficiency in the cord blood of neonates and the frequency of this deficiency in the etiology of neonatal hyperbilirubinemia. Material and Method: The study was performed consecutive 1015 neonates were included. Five hundred fifty six (54.8% of them were male and 459 (45.2% were female. The following parameters were recorded: Gender, birth weight, birth height, head circumference and gestational age. The glucose-6-phosphate dehydrogenase level of neonates were measured with quantitative method in cord blood. Also, hemoglobine, hematocrite, red blood cell count and blood group were measured. The following parameters were recorded in cases with jaundice: exchange transfusion, phototherapy, physiologic and pathologic jaundice, peak bilirubin day, maximum bilirubin level, total bilirubin level at the first day of jaundice, beginning time of jaundice. Results: Enzyme deficiency was detected in 133 (13.1% of neonates and 76 (57% of them were male, 57 (43% were female. Significant difference was detected in low glucose-6-phosphate dehydrogenase enzyme level with jaundice group for total bilirubin level at the first day of jaundice, maximum total bilirubin level and pathologic jaundice (p<0.05. Discussion: The ratio of glucose-6-phosphate dehydrogenase deficiency was found in Edirne in this study and this ratio was higher than other studies conducted in our country. For this reason, glucose-6-phosphate dehydrogenase enzyme level in cord blood of neonates should be measured routinely and high risk neonates should be followed up for hyperbilirubinemia and parents should be informed in our region.

ACCUMULATION OF SELECTED METALS IN UMBILICAL CORD BLOOD OF NULLIPAROUS AND MULTIPAROUS WOMEN AND CORRELATION WITH THE NEWBORN´S PARAMETERS

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Iwona Kozikowska

2012-08-01

Full Text Available The aim of this study was to determine the content of magnesium, copper, cadmium and iron in umbilical cord blood of the newborns depending on the number of pregnancies. It was established correlations between average concentrations these metals in cord blood and newborn’s parameters. The study material was collected immediately after delivery from the Department of Obstetrics and Gynecology in Bytom. The cord blood was taken from 99 women between 29-40 years old. Women were divided into two groups: nulliparous and multiparous. The concentration of metals in the cord blood was determined by flame atomic absorption spectrometry (FAAS. The conducted study demonstrates that magnesium, copper, cadmium and iron were noted in all tissues, both nulliparous women and multiparous mothers. The maximum concentration of cadmium in umbilical cord blood was observed among multiparous mothers (2.229 mg.kg-1 d.m.. In group of nulliparous women was observed higher concentration of Fe, Mg and Cu in umbilical cord blood than in multiparous mothers. It was noted some statistically significant correlation between iron, copper and newborn’s parameters. Parity influences the concentration of cadmium in umbilical cord blood with higher level found in multiparous women. Average content of iron in cord blood did not decrease with parity, it indicate that this element is preferentially taken up by the child.

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.

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

International Nuclear Information System (INIS)

Unuvar, Emin; Ahmadov, Hasan; Kiziler, Ali Riza; Aydemir, Birsen; Toprak, Sadik; Ulker, Volkan; Ark, Cemal

2007-01-01

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, μg/L). Results: Mercury levels were 0.38 ± 0.5 μg/L (0-2.34) in venous blood of pregnant women, 0.50 ± 0.64 μg/L (0-2.36) in umbilical cord blood and 9.45 ± 13.8 μg/g (0-66.5) in meconium. Maternal blood mercury level was lower than the known toxic limit for humans (EPA, 5 μg/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

Maternal adiposity and maternal and cord blood concentrations of vitamin D [25(OHD3

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Fernanda F.A. Simões

2016-10-01

Full Text Available Obesity is associated with lower concentrations of vitamin D [25(OHD3] in children, adolescents and adults, but it remains unclear whether maternal adiposity influences maternal and foetal concentrations of this vitamin. The objective of this cross-sectional study was to assess the relationship between maternal adiposity and maternal and cord blood concentrations of vitamin D. It involved 101 mother–newborn pairs from a public maternity in Sao Paulo city, Brazil. Demographic, socioeconomic and obstetric data, as well as anthropometry, physical activity and vitamin D supplementation during pregnancy, were investigated. Maternal adiposity was assessed by bioelectrical impedance. Maternal and cord blood concentrations of vitamin D were measured by high-performance liquid chromatography. Two multiple linear regression models that included maternal and cord blood vitamin D concentrations as outcomes and maternal adiposity as independent variable were used. No association was observed between maternal adiposity and maternal or cord blood concentrations of vitamin D. Maternal vitamin D concentration was associated with race, physical activity and vitamin D supplementation (adj. R2 = 0.74. Cord blood vitamin D concentration was associated with maternal vitamin D concentration (adj. R2 = 0.24. Although fat mass quantification is important to understand vitamin D status during all stages of life, this may not be true in pregnancy as race, vitamin D supplementation and physical activity appeared to be more relevant to vitamin D status. Understanding vitamin D metabolism in pregnancy may elucidate how or if adiposity influences maternal vitamin D status and how it impacts vitamin D transport to the foetus.

The influence of gender- and age-related differences in the radiosensitivity of hematopoietic progenitor cells detected in steady-state human peripheral blood

International Nuclear Information System (INIS)

Kato, Kengo; Kashiwakura, Ikuo; Kuwabara, Mikinori

2011-01-01

To investigate the importance of gender and aging on the individual radiosensitivity of lineage-committed myeloid hematopoietic stem/progenitor cells (HSPCs) detected in mononuclear cells (MNCs) of steady-state human peripheral blood (PB), the clonogenic survival of HPCs, including colony-forming unit-granulocyte macrophage; burst-forming unit-erythroid; colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte cells derived from MNCs exposed to 0.5 Gy and 2 Gy X-irradiation were estimated. MNCs were prepared from the buffy-coats of 59 healthy individual blood donors. The results showed that large individual differences exist in the number of HSPCs, as well as in the surviving fraction of cells. Furthermore, the number of progenitor cells strongly correlated with their surviving fraction, suggesting that the radiosensitivity of hematopoietic progenitor cells decreases with the number of cells in the 10 5 cells population. A statistically significant negative correlation was observed between the surviving fraction observed at a dose of 0.5 Gy and the age of an individual, however, none of these correlations were observed after 2 Gy irradiation. No statistically significant difference was observed in individual radiosensitivity between males and females at either radiation dose. The present results indicated a correlation between the individual responsiveness of HSPCs to ionizing irradiation, especially to low dose irradiation, and aging. (author)

In vitro transdifferentiation of umbilical cord stem cells into cardiac myocytes: Role of growth factors

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Rasha A.M. Khattab

2013-04-01

Full Text Available Recently, stem cell based cell therapy has become a realistic option to replace damaged cardiomyocytes. Most studies on stem cell transplantation therapy have focused on the use of undifferentiated stem cells. There is a strong possibility that some cardiogenic differentiation of the stem cell in vitro prior to transplantation would result in higher engraftment efficiency, as well as enhanced myocardial regeneration and recovery of heart function. In this study we aimed to define the conditions for ex-vivo differentiation of cord blood stem cells to cardiomyocytes and endothelial cells. These conditions include the combination of vascular endothelial growth factor (VEGF; basic fibroblast growth factor (FGF-2 and platelet derived growth factor AB (PDGF-AB. Forty cord blood samples were included in this work. In this work, the percentage of CD34+ cells, CD31+ cells and CD34/31+ cells in mononuclear cells (MNC suspension was counted prior to culture (day zero, and day 10 in the different growth factor cocktails used as well as the control tube, from which the fold increase of CD34+ cells, CD31+ cells and CD34/31+ cells was calculated. Detection of cardiac troponin I in the cultured cells to confirm cardiac differentiation was done at day 10 using Mouse anti-troponin I monoclonal antibody. From the present study, it was concluded that the growth factor cocktail in protocol 2 (FGF2+VEGF+PDGF-AB gives better in vitro trans-differentiation of stem/progenitor cells in umbilical cord blood into cardiomyocytes and endothelial cells than the cytokines cocktail in protocol 1 (FGF2+VEGF alone.

[Stem and progenitor cells in biostructure of blood vessel walls].

Science.gov (United States)

Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

2013-09-18

Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Stem and progenitor cells in biostructure of blood vessel walls

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Krzysztof Korta

2013-09-01

Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Impact of delayed umbilical cord clamping on public cord blood donations: can we help future patients and benefit infant donors?

Science.gov (United States)

Ciubotariu, Rodica; Scaradavou, Andromachi; Ciubotariu, Ilinca; Tarnawski, Michal; Lloyd, Sara; Albano, Maria; Dobrila, Ludy; Rubinstein, Pablo; Grunebaum, Amos

2018-03-25

Cord blood (CB) is a widely accepted stem cell source and its clinical utilization depends, to a great extent, on its cell content. Birth-to-clamping (BTC) time of umbilical cord determines placental transfusion to the newborn, and the remaining blood that can be collected and banked. The 2017 Committee Opinion of the American College of Obstetrics and Gynecologists (ACOG) recommends a delay of "at least 30-60 seconds" before clamping the cord for all newborns to ensure adequate iron stores. The impact of delayed cord clamping (DCC) on public CB banking can be substantial. Cord blood units (CBUs) collected from 1210 mothers at one hospital were evaluated for total nucleated cells (TNCs) and weight/volume based on time to clamping. Bank staff recorded BTC time in seconds as reported by obstetricians; collections were performed ex utero. Immediate clamping was defined as BTC of less than 30 seconds, whereas DCC was defined as BTC of 30 seconds or more. Cord clamping was immediate in 903 (75%) and delayed in 307 (25%) deliveries. Successful recovery (% clinical CBUs) decreased 10-fold with DCC of more than 60 seconds (22% vs. 2.4%, p < 0.001). CBUs collected after DCC of more than 60 seconds had significantly lower TNC counts than those after DCC of less than 60 seconds (p < 0.0001). Furthermore, 38% to 46% of CBUs after DCC of more than 60 seconds had volume of less than 40 mL. Our study indicates that DCC of 30 to 60 seconds has a small negative impact on collection of high-TNC-count CBUs. However, increasing BTC to more than 60 seconds decreases significantly both TNC content and volume, reducing drastically the chances of obtaining clinically useful CBUs. © 2018 AABB.

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

to be less precise than suggested by laboratory quality data, we studied the interrelationships of mercury concentrations with hemoglobin in paired maternal and cord blood samples from a Faroese birth cohort (N=514) and the Mothers and Children[U+05F3]s Environmental Health study in Korea (n=797). Linear...... and cord blood for hemoglobin improved their precision, while no significant effect of the selenium concentration in maternal blood was found. Adjustment of blood-mercury concentrations for hemoglobin is therefore recommended. © 2014 Elsevier Inc....

Outcome prediction value of determination of cord blood ADM concentrations in neonates with perinatal asphyxia events

International Nuclear Information System (INIS)

Zhang Shifa; Zhou Mingxiong; Zhang Xinlu

2006-01-01

Objective: To investigate the clinical value of determination of cord blood adrenomedullin (ADM) concentration for predicting development of hypoxic ischemic encephalopathy (HIE) in neonates suffered from perinatal asphyxia. Methods: Cord blood plasma ADM concentrations were measured with RIA in 77 full-ferm neonates with perinatal asphyxia and 30 controls. Results: In the 77 neonates with perinatal asphyxia, 32 developed clinical evidence of HIE within 7 days after birth (HIE group) and 45 didn't (non-HIE group). Cord blood plasma ADM concentrations in the HIE group (160.30 ± 41.3pg/ml) were significantly higher than those in the non-HIE group (112.26 ± 22.90 pg/ml) and controls (102.90 ± 19.43pg/ml). The cord blood plasma ADH concentrations in HIE group were also significantly positively correlated with the severity of the disease (r s = 0. 752, P < 0. 01 ). From our data, taking 117.93pg/ml as cut-off value for diagnosis of HIE would result in a sensitivity of 90.63%, specificity of 80%, and accuracy of 84.42%. Conclusion: High level of ADM in cord blood of neonates with perinatal asphyxia (≥117.93pg/ml) would predict development of HIE with a reasonable accuracy. (authors)

Umbilical Cord Blood pH in Intrapartum Hypoxia.

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Perveen, Fouzia; Khan, Ayesha; Ali, Tahmina; Rabia, Syeda

2015-09-01

To determine the association of cord arterial blood pH with neonatal outcome in cases of intrapartum fetal hypoxia. Descriptive analytical study. Gynaecology Unit-II, Civil Hospital, Karachi, from September 2011 to November 2012. All singleton cephalic fetuses at term gestation were included in the study. Those with any anomaly, malpresentation, medical disorders, maternal age 7.25, neonatal outcome measures (healthy, NICU admission or neonatal death), color of liquor and mode of delivery recorded on predesigned proforma. Statistical analysis performed by SPSS 16 by using independent-t test or chi-square test and ANOVA test as needed. A total of 204 newborns were evaluated. The mean pH level was found to be significantly different (p=0.007) in two groups. The pH value 7.25 had significant association (p 7.25. Majority (63.6%) cases needed caesarean section as compared to 31.4% controls. There is a significant association of cord arterial blood pH at birth with neonatal outcome at pH 7.25; but below the level of pH 7.25 it is still inconclusive.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

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Adams, Zachary; Morris, Gail; Campbell, Todd; Mostert, Karen; Dibdin, Nicholas; Fearon, Margaret; Elmoazzen, Heidi; Mercer, Dena; Young, Kimberly; Allan, David

2018-04-01

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

[Complete blood count reference values of donated cord blood from Korean neonates].

Science.gov (United States)

Lee, Hye Ryun; Shin, Sue; Yoon, Jong Hyun; Kim, Byoung Jae; Hwang, Kyu Ri; Kim, Jin Ju; Roh, Eun Youn

2009-06-01

In the public cord blood (CB) banks, only safe CB units with adequate cell doses are processed and stored. Complete blood count (CBC) of CB is crucial for estimating total nucleated cells (TNC) and screening suitable CB units without hematologic abnormalities. We analyzed CBC parameters of the donated CB from healthy Korean neonates to establish CBC reference values. A total of 2,129 Korean CB units, donated and processed during the period from August 2007 to December 2007, were enrolled. We measured hemoglobin (Hb), white blood cell (WBC) count, differential count of WBC, platelets and nucleated red blood cell (nRBC) count by XE-2100 automated hematology analyzer (Sysmex, Japan), and estimated reference value of each parameter by using parametric (Mean+/-2SD) and/or non-parametric methods (2.5-97.5 percentile). And also, we compared the result of each parameter in relation to sex of neonates and delivery method. Because the differences of CBC values among different subgroups were not remarkable, we established the reference intervals as follows without subgroup division: Hb, 9.0-14.4 g/dL; WBC count, 5.6-18.5 x 10(3)/microL; differential count of WBC (neutrophils, 40.8-72.4%; lymphocytes, 17.2-46.7%; monocytes, 4.9-12.8%; eosinophils, 0.7-7.0%; basophils, 0.0-1.6%); platelet, 130-287 x 10(3)/microL; nRBCs, 0.0-13.1/100 WBC. We established cord blood CBC reference values of healthy Korean neonates using a large-scale CB units. The established CBC reference values from our study will be useful as basic data for CBC interpretation and assessment of transplant suitability of donated CB.

Polybrominated diphenyl ethers (PBDEs) and thyroid hormones in cord blood

International Nuclear Information System (INIS)

Ding, Guodong; Yu, Jing; Chen, Limei; Wang, Caifeng; Zhou, Yijun; Hu, Yi; Shi, Rong; Zhang, Yan; Cui, Chang; Gao, Yu; Tian, Ying; Liu, Fang

2017-01-01

Human exposure to polybrominated diphenyl ethers (PBDEs) has been increasing over the last three decades in China and around the world. Animal studies suggest that PBDEs could reduce blood levels of thyroid hormones, but it is unclear whether PBDEs disrupt thyroid function in humans. We used data from a prospective birth cohort of 123 pregnant women who were enrolled between September 2010 and March 2011 in Shandong, China. We measured the concentrations of eight PBDE congeners (n = 106) and five thyroid hormones (n = 107) in cord serum samples. We examined the relationship between prenatal exposure to PBDEs and thyroid function (n = 90). Median concentrations of BDEs 47, 99, 100, and 153 (detection frequencies > 75%) were 3.96, 8.27, 3.31, and 1.89 ng/g lipid, respectively. A 10-fold increase in BDE-99 and Σ 4 PBDEs (the sum of BDEs 47, 99, 100, and 153) concentrations was associated with a 0.41 μg/dL (95% confidence interval [CI]: 0.10 to 0.72) and 0.37 μg/dL (95% CI: 0.06 to 0.68) increase in total thyroxine levels (TT 4 ), respectively. No associations were found between other individual congeners and any of the five thyroid hormones. Our study suggests that prenatal exposure to PBDEs may be associated with higher TT 4 in cord blood. Given the inconsistent findings across existing studies, our results need to be confirmed in additional studies. - Highlights: • Human exposure to PBDEs has been increased over recent decades in China. • PBDEs reduce thyroid hormones in animal studies, but it is unclear in humans. • We examined the relation of PBDE levels with thyroid hormones in cord blood. • Prenatal exposure to PBDEs is associated with higher total thyroxine levels. • The findings may have implications for fetal development. - Exposure to PBDEs is associated with higher total thyroxine levels in cord blood, and the findings may have implications for fetal development.

Effect of low dose irradiation on expression of membrane molecules of T lymphocytes in cord blood

International Nuclear Information System (INIS)

Liu Chang'an; Yang Guang; Jia Tingzhen

2001-01-01

The membrane molecules expression of T lymphocytes of cord blood after low dose irradiation (LDI) was investigated. Freshly isolated lymphocytes from cord blood were irradiated with 62 mGy γ-ray. At different time (4 h, 12 h, 24 h) after irradiation the changes of TCR + , CD3 + , CD4 + , CD8 + cells were examined by flow cytometry with direct immunofluorescence, respectively. The experimental results showed that the proportion of CD3 + , TCR + /CD3 + , CD4 + , CD8 + cells increased significantly after LDI, with the most obvious enhancement noted in the 24 h experimental group. The ratio of CD4 to CD8 showed no significant changes. It is suggested that expedition of the maturation, activation and signal transduction of T lymphocytes from cord blood can be induced by irradiation of 62 mGy γ-ray. So the reconstruction of immune functions after cord blood transplantation can be accelerated, enhancing the graft versus leukemia (GVL) effect and preventing the tumor from relapsing

Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

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Natalia Malinovskaya

2016-12-01

Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization.

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Bhang, Suk Ho; Lee, Seahyoung; Shin, Jung-Youn; Lee, Tae-Jin; Kim, Byung-Soo

2012-10-01

Despite promising results from the therapeutic use of stem cells for treating ischemic diseases, the poor survival of cells transplanted into ischemic regions is one of the major problems that undermine the efficacy of stem cell therapy. Cord blood mononuclear cells (CBMNCs) are an alternative source of mesenchymal stem cells (MSCs) without disadvantages, such as the painful and invasive harvesting procedure, of MSCs derived from bone marrow or adipose tissue. In the present study, we investigated whether the angiogenic efficacy of cord blood mesenchymal stem cells (CBMSCs) can be enhanced by grafting as spheroids in a mouse hindlimb ischemia model. Human CBMSC (hCBMSC) spheroids were prepared by using the hanging-drop method. Mouse hindlimb ischemia was induced by excising the femoral artery and its branches. After surgery, the animals were divided into no-treatment, dissociated hCBMSC, and spheroid hCBMSC groups (n=8 per group) and received corresponding hCBMSC treatments. After surgery, the ischemic hindlimbs were monitored for 4 weeks, and then, the ischemic hindlimb muscles were harvested for histological analysis. Apoptotic signaling, angiogenesis-related signal pathways, and blood vessel formation were investigated in vitro and/or in vivo. The transplantation of hCBMSCs as spheroids into mouse ischemic hindlimbs significantly improved the survival of the transplanted cells by suppressing apoptotic signaling while activating antiapoptotic signaling. Furthermore, the transplantation of hCBMSCs as spheroids significantly increased the number of microvessels and smooth muscle α-actin-positive vessels in the ischemic limbs of mice, and attenuated limb loss and necrosis. Human CBMNC can be considered an alternative source of MSC, and spheroid-based hCBMSC delivery can be considered a simple and effective strategy for enhancing the therapeutic efficacy of hCBMSCs.

MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors

NARCIS (Netherlands)

Giacomazzi, G. (Giorgia); Holvoet, B. (Bryan); Trenson, S. (Sander); Caluwé, E. (Ellen); Kravic, B. (Bojana); Grosemans, H. (Hanne); Cortés-Calabuig, Á. (Álvaro); Deroose, C.M. (Christophe M.); D. Huylebroeck (Danny); Hashemolhosseini, S. (Said); S. Janssens (Stefan); McNally, E. (Elizabeth); Quattrocelli, M. (Mattia); Sampaolesi, M. (Maurilio)

2017-01-01

textabstractMuscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types

Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort.

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Fleisch, Abby F; Rifas-Shiman, Sheryl L; Rokoff, Lisa B; Hivert, Marie-France; Mantzoros, Christos S; Oken, Emily

2017-07-01

Maternal smoking during pregnancy is associated with low fetal growth and adverse cardiometabolic health in offspring. However, hormonal pathways underlying these associations are unclear. Therefore, we examined maternal smoking habits and umbilical cord blood hormone profiles in a large, prospective cohort. We studied 978 mother/infant pairs in Project Viva, a Boston-area cohort recruited 1999-2002. We categorized mothers as early pregnancy smokers, former smokers, or never smokers. Outcomes were cord blood concentrations of IGF-1, IGF-2, IGFBP-3, leptin, adiponectin, insulin, and C-peptide. We used linear regression models adjusted for maternal pre-pregnancy body mass index (BMI), race/ethnicity, parity, education, and infant sex. We conducted analyses in the full cohort and stratified by infant sex. Thirteen percent of women were early pregnancy smokers, 20% former smokers, and 68% never smokers. Infants of early pregnancy smokers had lower IGF-1 adjusted for IGFBP-3 [-5.2ng/mL (95% CI: -8.6, -1.7)], with more pronounced associations in girls [-10.7ng/mL (95% CI: -18.5, -2.9) vs. -4.0ng/mL (95% CI: -8.4, 0.4) for boys]. Early pregnancy smoking was not associated with cord blood hormones other than IGF-1. Infants of former smokers had a cord blood hormone profile similar to infants of never smokers. As compared to mothers who never smoked, early pregnancy smokers had infants with lower cord blood IGF-1 which could prime adverse metabolic outcomes. This provides further reason to support smoking cessation programs in women of reproductive age. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of cell culture media conditions on the osteogenic differentiation of cord blood-derived mesenchymal stem cells.

Science.gov (United States)

Hildebrandt, Cornelia; Büth, Heiko; Thielecke, Hagen

2009-01-01

In this study the critical parameters directing osteogenic differentiation of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) were investigated, key factors and conditions identified and improved protocols for a more cell-type adapted differentiation developed. Today only little information about the specific conditions directing osteogenic development is available and current protocols for cultivation and differentiation of UCB-MSCs are based mainly on experience with bone marrow-derived MSCs (BM-MSCs) without further adaptation. Thus, protocols for improved osteoinduction are of particular interest. The goal of this study was to investigate the influence of three different culture media (A) alpha MEM, 15% FBS, (B) DMEM, 15% FBS and (C) MSCGM, 10% SingleQuot growth supplement on the osteogenic differentiation of UCB-MSCs. Moreover, a systematic analysis of two concentrations of dexamethasone (10(-8)M/10(-7)M) in combination with or without BMP-2 (10(-7)M) was carried out by detecting the expression of alkaline phosphatase (ALP), collagen-1 and the mineralization of ECM. We found that MSCGM, 10% SingleQuot had a supportive effect on the osteogenic differentiation of UCB-MSCs. In case of treatment with 10(-8)M dexamethasone, mineralization occurred in combination with BMP-2 exclusively, while a concentration of 10(-7)M dexamethasone led to a high amount of mineralized ECM and the expression of collagen-1 independent of BMP-2 addition. According to this data dexamethasone is the leading osteoinductive factor, but BMP-2 seems to have supportive properties in UCB-MSCs. In conclusion, MSCGM supplemented with 10% SingleQuot and 10(-7)M dexamethasone was the condition identified to be best for inducing the osteogenic differentiation of UCB-MSCs.

In vitro differentiation of human umbilical cord blood mesenchymal ...

African Journals Online (AJOL)

Mesenchymal stem cells (MSCs) were isolated by gradient density centrifugation from umbilical cord blood. Spindle-shaped adherent cells were permitted to grow to 70% confluence in primary culture media which was reached by day 12. Induction of differentiation started by culturing cells with differentiation medium ...

A Comparison of Bone Marrow and Cord Blood Mesenchymal Stem Cells for Cartilage Self-Assembly.

Science.gov (United States)

White, Jamie L; Walker, Naomi J; Hu, Jerry C; Borjesson, Dori L; Athanasiou, Kyriacos A

2018-04-02

Joint injury is a common cause of premature retirement for the human and equine athlete alike. Implantation of engineered cartilage offers the potential to increase the success rate of surgical intervention and hasten recovery times. Mesenchymal stem cells (MSCs) are a particularly attractive cell source for cartilage engineering. While bone marrow-derived MSCs (BM-MSCs) have been most extensively characterized for musculoskeletal tissue engineering, studies suggest that cord blood MSCs (CB-MSCs) may elicit a more robust chondrogenic phenotype. The objective of this study was to determine a superior equine MSC source for cartilage engineering. MSCs derived from bone marrow or cord blood were stimulated to undergo chondrogenesis through aggregate redifferentiation and used to generate cartilage through the self-assembling process. The resulting neocartilage produced from either BM-MSCs or CB-MSCs was compared by measuring mechanical, biochemical, and histological properties. We found that while BM constructs possessed higher tensile properties and collagen content, CB constructs had superior compressive properties comparable to that of native tissue and higher GAG content. Moreover, CB constructs had alkaline phosphatase activity, collagen type X, and collagen type II on par with native tissue suggesting a more hyaline cartilage-like phenotype. In conclusion, while both BM-MSCs and CB-MSCs were able to form neocartilage, CB-MSCs resulted in tissue more closely resembling native equine articular cartilage as determined by a quantitative functionality index. Therefore, CB-MSCs are deemed a superior source for the purpose of articular cartilage self-assembly.

Production of hemizygous and homozygous embryonic stem cell-derived neural progenitor cells from the transgenic alszheimer göttingen minipis

DEFF Research Database (Denmark)

Hall, Vanessa Jane; Jacobsen, J.; Gunnarsson, A.

2011-01-01

Production of hemizygous and homozygous embryonic stem cell-derived neural progenitor cells from the transgenic alszheimer göttingen minipis......Production of hemizygous and homozygous embryonic stem cell-derived neural progenitor cells from the transgenic alszheimer göttingen minipis...

Ex-Vivo Gene Therapy Using Lentiviral Mediated Gene Transfer Into Umbilical Cord Blood Derived Stem Cells

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Hanieh Jalali

2016-02-01

Full Text Available Background Introduction of therapeutic genes into the injured site of nervous system can be achieved using transplantation of cellular vehicles containing desired gene. To transfer exogenous genes into the cellular vehicles, lentiviral vectors are one of interested vectors because of advantages such high transduction efficiency of dividing and non-dividing cells. Unrestricted somatic stem cells are subclasses of umbilical cord blood derived stem cells which are appreciate candidates to use as cellular vehicles for ex vivo gene therapy of nervous system. Objectives In current study we investigated the effect of lentiviral vector transduction on the neuronal related features of unrestricted somatic stem cells to indicate the probable and unwanted changes related to transduction procedure. Materials and Methods In this experimental study, lentiviral vector containing green fluorescent protein (GFP were transduced into unrestricted somatic stem cells and its effect was investigated with using MTT assay, qPCR and immunohistochemistry techniques. For statistical comparison of real time PCR results, REST software (2009, Qiagen was used. Results Obtained results showed lentiviral vector transduction did not have cytotoxic effects on unrestricted somatic stem cells and did not change neuronal differentiation capacity of them as well the expression of some neuronal related genes and preserved them in multilineage situation. Conclusions In conclusion, we suggested that lentiviral vectors could be proper vectors to transfer therapeutic gene into unrestricted somatic stem cells to provide a cellular vehicle for ex vivo gene therapy of nervous system disorders.

Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

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Teruyo Oishi

Full Text Available Heterotopic ossification (HO is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+ and PDGFRα(+ cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+ cells and PDGFRα(+ cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+ cells formed bone-like tissue and showed successful engraftment, while CD56(+ cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+ cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+ cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+ cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+ cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+ cells. Our results suggest that PDGFRα(+ cells may be the major source of HO and that the newly identified mi

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

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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.

Endothelial progenitor cell subsets and preeclampsia: Findings and controversies

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Armin Attar

2017-10-01

Full Text Available Vascular remodeling is an essential component of gestation. Endothelial progenitor cells (EPCs play an important role in the regulation of vascular homeostasis. The results of studies measuring the number of EPCs in normal pregnancies and in preeclampsia have been highly controversial or even contradictory because of some variations in technical issues and different methodologies enumerating three distinct subsets of EPCs: circulating angiogenic cells (CAC, colony forming unit endothelial cells (CFU-ECs, and endothelial colony-forming cells (ECFCs. In general, most studies have shown an increase in the number of CACs in the maternal circulation with a progression in the gestational age in normal pregnancies, while functional capacities measured by CFU-ECs and ECFCs remain intact. In the case of preeclampsia, mobilization of CACs and ECFCs occurs in the peripheral blood of pregnant women, but the functional capacities shown by culture of the derived colony-forming assays (CFU-EC and ECFC assays are altered. Furthermore, the number of all EPC subsets will be reduced in umbilical cord blood in the case of preeclampsia. As EPCs play an important role in the homeostasis of vascular networks, the difference in their frequency and functionality in normal pregnancies and those with preeclampsia can be expected. In this review, there was an attempt to provide a justification for these controversies.

Downregulation of Melanoma Cell Adhesion Molecule (MCAM/CD146) Accelerates Cellular Senescence in Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

Science.gov (United States)

Jin, Hye Jin; Kwon, Ji Hye; Kim, Miyeon; Bae, Yun Kyung; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Jeon, Hong Bae

2016-04-01

Therapeutic applications of mesenchymal stem cells (MSCs) for treating various diseases have increased in recent years. To ensure that treatment is effective, an adequate MSC dosage should be determined before these cells are used for therapeutic purposes. To obtain a sufficient number of cells for therapeutic applications, MSCs must be expanded in long-term cell culture, which inevitably triggers cellular senescence. In this study, we investigated the surface markers of human umbilical cord blood-derived MSCs (hUCB-MSCs) associated with cellular senescence using fluorescence-activated cell sorting analysis and 242 cell surface-marker antibodies. Among these surface proteins, we selected the melanoma cell adhesion molecule (MCAM/CD146) for further study with the aim of validating observed expression differences and investigating the associated implications in hUCB-MSCs during cellular senescence. We observed that CD146 expression markedly decreased in hUCB-MSCs following prolonged in vitro expansion. Using preparative sorting, we found that hUCB-MSCs with high CD146 expression displayed high growth rates, multilineage differentiation, expression of stemness markers, and telomerase activity, as well as significantly lower expression of the senescence markers p16, p21, p53, and senescence-associated β-galactosidase, compared with that observed in hUCB-MSCs with low-level CD146 expression. In contrast, CD146 downregulation with small interfering RNAs enhanced the senescence phenotype. In addition, CD146 suppression in hUCB-MSCs caused downregulation of other cellular senescence regulators, including Bmi-1, Id1, and Twist1. Collectively, our results suggest that CD146 regulates cellular senescence; thus, it could be used as a therapeutic marker to identify senescent hUCB-MSCs. One of the fundamental requirements for mesenchymal stem cell (MSC)-based therapies is the expansion of MSCs during long-term culture because a sufficient number of functional cells is required

Multicentre standardisation of a clinical grade procedure for the preparation of allogeneic platelet concentrates from umbilical cord blood

Science.gov (United States)

Rebulla, Paolo; Pupella, Simonetta; Santodirocco, Michele; Greppi, Noemi; Villanova, Ida; Buzzi, Marina; De Fazio, Nicola; Grazzini, Giuliano

2016-01-01

Background In addition to a largely prevalent use for bleeding prophylaxis, platelet concentrates from adult blood have also been used for many years to prepare platelet gels for the repair of topical skin ulcers. Platelet gel can be obtained by activation of fresh, cryopreserved, autologous or allogeneic platelet concentrates with calcium gluconate, thrombin and/or batroxobin. The high content of tissue regenerative factors in cord blood platelets and the widespread availability of allogeneic cord blood units generously donated for haematopoietic transplant but unsuitable for this use solely because of low haematopoietic stem cell content prompted us to develop a national programme to standardise the production of allogeneic cryopreserved cord blood platelet concentrates (CBPC) suitable for later preparation of clinical-grade cord blood platelet gel. Materials and methods Cord blood units collected at public banks with total nucleated cell counts 150×109/L and volume >50 mL, underwent soft centrifugation within 48 hours of collection. Platelet-rich plasma was centrifuged at high speed to obtain a CBPC with target platelet concentration of 800–1,200×109/L, which was cryopreserved, without cryoprotectant, below −40 °C. Results During 14 months, 13 banks produced 1,080 CBPC with mean (± standard deviation) volume of 11.4±4.4 mL and platelet concentration of 1,003±229×109/L. Total platelet count per CBPC was 11.3±4.9×109. Platelet recovery from cord blood was 47.7±17.8%. About one-third of cord blood units donated for haematopoietic transplant could meet the requirements for preparation of CBPC. The cost of preparation was € 160.92/CBPC. About 2 hours were needed for one technician to prepare four CBPC. Discussion This study yielded valuable scientific and operational information regarding the development of clinical trials using allogeneic CBPC. PMID:26509822

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

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Naosuke Kamei

2017-01-01

Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

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

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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.

Curcumin Increase the Expression of Neural Stem/Progenitor Cells and Improves Functional Recovery after Spinal Cord Injury

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Bang, Woo-Seok; Kim, Kyoung-Tae; Seo, Ye Jin; Cho, Dae-Chul; Sung, Joo-Kyung; Kim, Chi Heon

2018-01-01

Objective To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. Methods Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. Results The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p<0.05). The co-immunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p<0.05). Conclusion These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties. PMID:29354231

Hematopoietic Stem and Progenitor Cell Expansion in Contact with Mesenchymal Stromal Cells in a Hanging Drop Model Uncovers Disadvantages of 3D Culture.

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Schmal, Olga; Seifert, Jan; Schäffer, Tilman E; Walter, Christina B; Aicher, Wilhelm K; Klein, Gerd

2016-01-01

Efficient ex vivo expansion of hematopoietic stem cells with a concomitant preservation of stemness and self-renewal potential is still an unresolved ambition. Increased numbers of methods approaching this issue using three-dimensional (3D) cultures were reported. Here, we describe a simplified 3D hanging drop model for the coculture of cord blood-derived CD34(+) hematopoietic stem and progenitor cells (HSPCs) with bone marrow-derived mesenchymal stromal cells (MSCs). When seeded as a mixed cell suspension, MSCs segregated into tight spheroids. Despite the high expression of niche-specific extracellular matrix components by spheroid-forming MSCs, HSPCs did not migrate into the spheroids in the initial phase of coculture, indicating strong homotypic interactions of MSCs. After one week, however, HSPC attachment increased considerably, leading to spheroid collapse as demonstrated by electron microscopy and immunofluorescence staining. In terms of HSPC proliferation, the conventional 2D coculture system was superior to the hanging drop model. Furthermore, expansion of primitive hematopoietic progenitors was more favored in 2D than in 3D, as analyzed in colony-forming assays. Conclusively, our data demonstrate that MSCs, when arranged with a spread (monolayer) shape, exhibit better HSPC supportive qualities than spheroid-forming MSCs. Therefore, 3D systems are not necessarily superior to traditional 2D culture in this regard.

Early predictive value of cord blood bilirubin and dynamic monitoring of transcutaneous bilirubin for hyperbilirubinemia of newborns

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Haishan Guan

2017-12-01

Conclusions: The increase of cord blood bilirubin effectively predict the occurrence of neonatal hyperbilirubinemia. There is a good correlation between levels of transcutaneous bilirubin and serum bilirubin. Moreover, combined detection of transcutaneous bilirubin and cord blood bilirubin can significantly improve the prediction accuracy of hyperbilirubinemia.

Can pancreatic duct-derived progenitors be a source of islet regeneration?

International Nuclear Information System (INIS)

Xia, Bing; Zhan, Xiao-Rong; Yi, Ran; Yang, Baofeng

2009-01-01

The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in type 1 diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet β-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for

Can pancreatic duct-derived progenitors be a source of islet regeneration?

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Xia, Bing [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Zhan, Xiao-Rong, E-mail: xiaorongzhan@sina.com [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yi, Ran [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yang, Baofeng [Department of Pharmacology, State Key Laboratory of Biomedicine and Pharmacology, Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China)

2009-06-12

The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing {beta}-cells. The functional mass of {beta}-cells is decreased in type 1 diabetes, so replacing missing {beta}-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the {beta}-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding {beta}-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet {beta}-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal

Organochlorine pesticide levels in umbilical cord blood of newborn in Veracruz, Mexico.

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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.

Programming of Adiposity in Childhood and Adolescence: Associations With Birth Weight and Cord Blood Adipokines.

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Simpson, Joy; Smith, Andrew D A C; Fraser, Abigail; Sattar, Naveed; Lindsay, Robert S; Ring, Susan M; Tilling, Kate; Davey Smith, George; Lawlor, Debbie A; Nelson, Scott M

2017-02-01

Exposure to maternal adiposity during pregnancy is associated with higher offspring birth weight and greater adiposity through childhood and adult life. As birth weight reflects the summation of lean and fat mass, the extent to which fat mass at birth tracks into later life is unknown. To determine whether fat mass at birth is associated with child and adolescent adiposity. UK birth cohort with markers of neonatal fat mass; cord blood leptin, adiponectin, and birth weight and adiposity outcomes at age 9 (n = 2775) and 17 years (n = 2138). Offspring body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry-determined fat mass, and obesity at age 9 and 17 years. Higher cord blood leptin was associated with higher z scores of fat mass [difference in mean per 10 pg/mL: 0.03 standard deviation (SD); 95% confidence interval (CI), 0.00 to 0.06], waist circumference (0.04 SD; 95% CI, 0.00 to 0.07), and BMI (0.04 SD; 95% CI, 0.00 to 0.08) at age 9. However, by age 17 the adjusted results were attenuated to the null. Cord blood adiponectin was not associated with measures of adiposity at age 9. At age 17, cord blood adiponectin was positively associated with fat mass (0.02 SD per 10 μg/mL; 95% CI, 0.02 to 0.03) and waist circumference (0.04 SD per 10 μg/mL; 95% CI, 0.03 to 0.05). Birth weight was positively associated with waist circumference (0.03 SD per 100 g; 95% CI, 0.02 to 0.04) and BMI (0.02 SD per 100 g; 95% CI, 0.00 to 0.03), but not fat mass or odds of obesity. Cord blood leptin and adiponectin were not associated with obesity at either age. Increased cord blood leptin and adiponectin, known surrogates of fetal fat mass, were weakly associated with increased fat mass in late childhood and adolescence, respectively.

Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation.

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Pauwels, Sara; Ghosh, Manosij; Duca, Radu Corneliu; Bekaert, Bram; Freson, Kathleen; Huybrechts, Inge; A S Langie, Sabine; Koppen, Gudrun; Devlieger, Roland; Godderis, Lode

2017-01-02

Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methyl-group donors was assessed using a food-frequency questionnaire. LC-MS/MS and pyrosequencing were used to measure global and gene specific methylation, respectively. Dietary intake of methyl-groups before and during pregnancy was associated with changes in LEP, DNMT1, and RXRA cord blood methylation. Statistically significant higher cord blood LEP methylation was observed when mothers started folic acid supplementation more than 6 months before conception compared with 3-6 months before conception (34.6 ± 6.3% vs. 30.1 ± 3.6%, P = 0.011, LEP CpG1) or no folic acid used before conception (16.2 ± 4.4% vs. 13.9 ± 3%, P = 0.036 for LEP CpG3 and 24.5 ± 3.5% vs. 22.2 ± 3.5%, P = 0.045 for LEP mean CpG). Taking folic acid supplements during the entire pregnancy resulted in statistically significantly higher cord blood RXRA methylation as compared with stopping supplementation in the second trimester (12.3 ± 1.9% vs. 11.1 ± 2%, P = 0.008 for RXRA mean CpG). To conclude, long-term folic acid use before and during pregnancy was associated with higher LEP and RXRA cord blood methylation, respectively. To date, pregnant women are advised to take a folic acid supplement of 400 µg/day from 4 weeks before until 12 weeks of pregnancy. Our results suggest significant epigenetic modifications when taking a folic acid supplement beyond the current advice.

Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

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Li-Li Wang

Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

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

Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice

International Nuclear Information System (INIS)

Shima, Haruko; Takubo, Keiyo; Iwasaki, Hiroko; Yoshihara, Hiroki; Gomei, Yumiko; Hosokawa, Kentaro; Arai, Fumio; Takahashi, Takao; Suda, Toshio

2009-01-01

Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2Rγ null (NOG) mice. Hypoxic culture (1% O 2 ) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34 + CD38 - cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.

Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors.

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Chandran, Priya; Le, Yevgeniya; Li, Yuhua; Sabloff, Mitchell; Mehic, Jelica; Rosu-Myles, Michael; Allan, David S

2015-04-01

The bone marrow microenvironment may be permissive to the emergence and progression of acute myeloid leukemia (AML). Studying interactions between the microenvironment and leukemia cells should provide new insight for therapeutic advances. Mesenchymal stromal cells (MSCs) are central to the maintenance of the hematopoietic niche. Here we compared the functions and gene expression patterns of MSCs derived from bone marrow aspirates of healthy donors and patients with AML. MSCs expanded from AML patients had heterogeneous morphology and displayed a wide range of proliferation capacity compared to MSCs from healthy controls. The ability of AML-MSCs to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired while the expression of genes associated with maintaining hematopoietic quiescence appeared to be increased in AML-MSCs compared to healthy donors. These results highlight important potential differences in the biologic profile of MSCs from AML patients compared to healthy donors that may contribute to the emergence or progression of leukemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability.

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Payne, Allison H; Hawryluk, Gregory W; Anzai, Yoshimi; Odéen, Henrik; Ostlie, Megan A; Reichert, Ethan C; Stump, Amanda J; Minoshima, Satoshi; Cross, Donna J

2017-12-01

Spinal cord injury (SCI) affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound (MRgFUS) as a non-invasive approach to increase permeability in the blood-spinal cord barrier (BSCB). We hypothesize that localized, controlled sonoporation of the BSCB by MRgFUS will aid delivery of therapeutics to the injury. Here, we report our preliminary findings for the ability of MRgFUS to increase BSCB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column was used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRgFUS blood spinal cord barrier opening. Then, in normal rats, MRgFUS was applied in combination with intravenously administered microbubbles to the spinal cord region. Permeability of the BSCB was indicated as signal enhancement by contrast administered prior to T1-weighted magnetic resonance imaging and verified by Evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10 rats tested. Two rats showed minor impairment indicating need for further refinement of parameters. No gross tissue damage was evident by histology. In this study, we have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined with microbubbles.

Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.

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Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal

2015-01-01

During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

Energy Technology Data Exchange (ETDEWEB)

Kasten, Annika; Siegmund, Birte J. [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany); Grüttner, Cordula [Micromod Partikeltechnologie GmbH, Warnemünde, D-18115 Rostock (Germany); Kühn, Jens-Peter [Department of Radiology and Neuroradiology, Greifswald University Medical Center, D-17475 Greifswald (Germany); Frerich, Bernhard, E-mail: bernhard.frerich@med.uni-rostock.de [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany)

2015-04-15

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation.

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

International Nuclear Information System (INIS)

Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

2015-01-01

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation

Umbilical Cord-Derived Mesenchymal Stem Cells for Hematopoietic Stem Cell Transplantation

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Yu-Hua Chao

2012-01-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is becoming an effective therapeutic modality for a variety of diseases. Mesenchymal stem cells (MSCs can be used to enhance hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, prevent and treat graft-versus-host disease, and repair tissue damage in patients receiving HSCT. Till now, most MSCs for human clinical application have been derived from bone marrow. However, acquiring bone-marrow-derived MSCs involves an invasive procedure. Umbilical cord is rich with MSCs. Compared to bone-marrow-derived MSCs, umbilical cord-derived MSCs (UCMSCs are easier to obtain without harm to the donor and can proliferate faster. No severe adverse effects were noted in our previous clinical application of UCMSCs in HSCT. Accordingly, application of UCMSCs in humans appears to be feasible and safe. Further studies are warranted.

Culture of hESC-derived pancreatic progenitors in alginate-based scaffolds.

Science.gov (United States)

Formo, Kjetil; Cho, Candy H-H; Vallier, Ludovic; Strand, Berit L

2015-12-01

The effect of alginate-based scaffolds with added basement membrane proteins on the in vitro development of hESC-derived pancreatic progenitors was investigated. Cell clusters were encapsulated in scaffolds containing the basement membrane proteins collagen IV, laminin, fibronectin, or extracellular matrix-derived peptides, and maintained in culture for up to 46 days. The cells remained viable throughout the experiment with no signs of central necrosis. Whereas nonencapsulated cells aggregated into larger clusters, some of which showed signs of morphological changes and tissue organization, the alginate matrix stabilized the cluster size and displayed more homogeneous cell morphologies, allowing culture for long periods of time. For all conditions tested, a stable or declining expression of insulin and PDX1 and an increase in glucagon and somatostatin over time indicated a progressive reduction in beta cell-related gene expression. Alginate scaffolds can provide a chemically defined, xeno-free and easily scalable alternative for culture of pancreatic progenitors. Although no increase in insulin and PDX1 gene expression after alginate-immobilized cell culture was seen in this study, further optimization of the matrix physicochemical and biological properties and of the medium composition may still be a relevant strategy to promote the stabilization or maturation of stem cell-derived beta cells. © 2015 Wiley Periodicals, Inc.

A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

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2016-08-15

donors and cord blood units W. Bochtler1, L. Gragert2, Z. I. Patel3, J. Robinson3,4, D. Steiner5, J. A. Hofmann6, J. Pingel6, A. Baouz7, A. Melis8, J...cord blood units for individual patients is of primary importance. This challenging search process is routinely performed in a donor registry or cord...term ‘ donor ’ to refer to donors of HSCs from bone marrow or peripheral blood and cord blood units and the term ‘ donor registry’ shall include cord blood

Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal cells in vitro--a pilot study.

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You, Hi-Jin; Namgoong, Sik; Han, Seung-Kyu; Jeong, Seong-Ho; Dhong, Eun-Sang; Kim, Woo-Kyung

2015-11-01

Our previous studies demonstrated that human bone marrow-derived mesenchymal stromal cells have great potential for wound healing. However, it is difficult to clinically utilize cultured stem cells. Recently, human umbilical cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have been commercialized for cartilage repair as a first cell therapy product that uses allogeneic stem cells. Should hUCB-MSCs have a superior effect on wound healing as compared with fibroblasts, which are the main cell source in current cell therapy products for wound healing, they may possibly replace fibroblasts. The purpose of this in vitro study was to compare the wound-healing activity of hUCB-MSCs with that of fibroblasts. This study was particularly designed to compare the effect of hUCB-MSCs on diabetic wound healing with those of allogeneic and autologous fibroblasts. Healthy (n = 5) and diabetic (n = 5) fibroblasts were used as the representatives of allogeneic and autologous fibroblasts for diabetic patients in the control group. Human UCB-MSCs (n = 5) were used in the experimental group. Cell proliferation, collagen synthesis and growth factor (basic fibroblast growth factor, vascular endothelial growth factor and transforming growth factor-β) production were compared among the three cell groups. Human UCB-MSCs produced significantly higher amounts of vascular endothelial growth factor and basic fibroblast growth factor when compared with both fibroblast groups. Human UCB-MSCs were superior to diabetic fibroblasts but not to healthy fibroblasts in collagen synthesis. There were no significant differences in cell proliferation and transforming growth factor-β production. Human UCB-MSCs may have greater capacity for diabetic wound healing than allogeneic or autologous fibroblasts, especially in angiogenesis. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy

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Howard R. Seay

2017-03-01

Full Text Available Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR. Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

Cord blood vitamin D and the risk of acute lower respiratory infection in Indigenous infants in the Northern Territory.

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Binks, Michael J; Smith-Vaughan, Heidi C; Marsh, Robyn; Chang, Anne B; Andrews, Ross M

2016-04-04

To assess vitamin D status in Indigenous mothers and infants in the Northern Territory, and to determine whether cord blood vitamin D levels are correlated with the risk of infant hospitalisation for acute lower respiratory infection (ALRI). Within a nested cohort of 109 Indigenous mother-infant pairs recruited between 2006 and 2011, we used liquid chromatography-mass spectrometry to measure vitamin D (25(OH)D3) levels in maternal blood during pregnancy (n = 33; median gestation, 32 weeks [range, 28-36 weeks]) and at birth (n = 106; median gestation, 39 weeks [range, 34-41 weeks]), in cord blood (n = 84; median gestation, 39 weeks [range, 36-41 weeks]), and in infant blood at age 7 months (n = 37; median age, 7.1 months [range, 6.6-8.1 months]). ALRI hospitalisations during the first 12 months of infancy, identified using International Classification of Diseases coding (J09-J22, A37-A37.9). Compared with mean 25(OH)D3 levels in maternal blood during pregnancy (104 nmol/L), mean levels were 23% lower in maternal blood at birth (80 nmol/L) and 48% lower in cord blood samples (54 nmol/L). The mean cord blood 25(OH)D3 concentration in seven infants subsequently hospitalised for an ALRI was 37 nmol/L (95% CI, 25-48 nmol/L), lower than the 56 nmol/L (95% CI, 51-61 nmol/L) in the 77 infants who were not hospitalised with an ALRI (P = 0.025). Cord blood 25(OH)D3 concentrations were about half those in maternal blood during the third trimester of pregnancy (about 7 weeks earlier). Most cord blood levels (80%) were classified as vitamin D insufficient (L) by existing guidelines, and were lower among infants who were subsequently hospitalised with an ALRI.