Placental Blood as a Source of Hematopoietic Stem Cells for Transplantation into Unrelated Recipients

Kurtzberg, Joanne; Laughlin, Mary J.; Graham, Michael; Smith, Clay; Olson, Janice F.; Halperin, Edward C.; Ciocci, Gilbert; Carrier, Carmelita; Stevens, Cladd E.; Rubinstein, Pablo

doi:10.1056/nejm199607183350303

Cited by 989 publications

(685 citation statements)

References 31 publications

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“…1,[7][8][9]12 Therefore, UCB, which is normally discarded, has been evaluated as a source of progenitor cells that can be used for the treatment of diseases potentially curable by bone marrow transplantation (BMT). [2][3][4] Major concerns for wider transplant application of UBC have been related to the low total number of progenitor cells obtained by a single collection. Therefore, many attempts are ongoing better to understand the biologic and immunologic characteristics of UCB progenitor cells and to evaluate potential for their ex vivo expansion.…”

Section: Figurementioning

confidence: 99%

“…4 Therefore, many attempts are ongoing to evaluate the possibility of expanding UCB progenitor cells [7][8][9]11 and SCF in combination with other CSFs has been proven as a relevant factor for amplification of those cells capable of hematopoietic engraftment. SCF has been reported to act in combination with a variety of CSFs to influence the development of early hematopoietic progenitor cells.…”

Section: Figurementioning

confidence: 99%

“…[1][2][3] Studies are under way to determine the feasibility of UCB banking for use in unrelated transplants. [3][4][5][6] However, the major concern for future transplant application in adult patients has been related to the low number of progenitor cells that could be obtained by a single UCB collection. Several studies suggested that UCB contains a higher proportion of hematopoietic progenitor cells as compared to adult BM [7][8][9] and therefore the lower number of nucleated cells, present in a single collection, might be compensated by a higher proportion of primitive cells.…”

Section: Introductionmentioning

confidence: 99%

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Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

et al. 1997

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Umbilical cord blood (UCB) is an attractive potential alternative to bone marrow (BM) as a source of hematopoietic progenitor cells since the number of progenitors in UCB is similar or even greater than that in normal BM. It was the aim of the present study to analyze the degree of immaturity of UCB progenitor cells. UCB mononuclear (MNC) and/or CD34 + cells were tested for surface antigen phenotype, expression of cytokines receptor, effect of stem cell factor (SCF) on colony growth, resistance to mafosfamide and replating potential. We have found that 34.9 ± 3.4% and 77.9 ± 2.6% of UCB CD34 + cells did not express CD38 and CD45RA antigens, respectively, suggesting that UCB contains a high proportion of immature progenitor cells. By means of three-color analysis, the receptor for SCF was detected on the majority of the CD34 + HLA-DR + subpopulation; in fact, 81.8% ± 4.3% of CD34 + HLA-DR + cells were defined as SCF low and 8.1 ± 1.5% as SCF high . Colony growth of MNC and CD34 + cells was enhanced by the addition of SCF to methylcellulose mixture, resulting in a statistically significant increase in CFU-GM and CFU-GEMM but not in BFU-E numbers. UCB progenitor cells showed a higher resistance to mafosfamide treatment, in comparison to BM; the addition of SCF to the culture medium resulted in a statistically significant increase in mafosfamide concentration required to inhibit 95% of colony growth (P р 0.05). Moreover, as shown by single colony transfer assays, the presence of SCF in primary cultures promoted a significantly higher replating potential for both untreated (42 ± 3.3% vs 21 ± 4.6%, P р 0.018) and mafosfamide-treated samples (62 ± 5.6% vs 44 ± 6.1%, P р 0.018). In conclusion, UCB is a source of progenitor cells with immature characteristics in terms of surface antigen expression, distribution of SCF receptor, resistance to mafosfamide and replating potential. Therefore, UCB progenitor cells represent an ideal candidate population for experimental programs involving gene transfer and ex vivo stem cell expansion.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

et al. 1997

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“…The results, to date, are encouraging and appear at least comparable to bone marrow or peripheral blood progenitor cells as the donor source for transplants [12,13]. Later, Rubenstein and others were the first to establish an unrelated cord blood bank from voluntary donors and then used the blood units from the bank for unrelated cord blood transplantation [19][20][21]. These events further emphasize the importance of umbilical cord blood banking for transplantation in the medical field and the growing interest with 330 published articles retrieved by online searching of the PubMED website (www.ncbi.nlm.nih.gov/pubmed) on January 11, 2011 using the term "umbilical cord blood banking".…”

Section: Introductionmentioning

confidence: 99%

Umbilical cord blood banking: an update

Butler

Menitove²

2011

J Assist Reprod Genet

101

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Background Umbilical cord blood is a potential vast source of primitive hematopoietic stem and progenitor cells available for clinical application to reconstitute the hematopoietic system and/or restore immunological function in affected individuals requiring treatment. Cord blood can be used as an alternative source for bone marrow transplantation and its use is developing into a new field of treatment for pediatric and adult patients presenting with hematological disorders, immunological defects and specific genetic diseases. Discussion More than 25,000 allogeneic cord blood transplantations have been performed worldwide since the first cord blood transplantation in 1988. There are two banking options for storing umbilical cord blood [private (family) and public]. Cord blood stored in private banks are used for either autologous or allogeneic transplants for the infant donor or related family members but private cord blood banks are not searchable or available to the public. More than 780,000 cord blood units are stored in over 130 private cord blood banks, worldwide, and over 400,000 units in more than 100 quality controlled public cord blood banks.Conclusions Researchers continue to evaluate the usefulness of cord blood cells in treating human diseases or disorders for purposes other than hematological disorders including heart disease, strokes, brain or spinal cord injuries and cancer. This review summarizes the status of umbilical cord blood banking, its history and current and potential use in the treatment of human disease.

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“…2 Although initial donors were siblings, more recently cord blood transplants from unrelated donors have been used, and international umbilical cord blood banks have already been established in Europe and in the USA.…”

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Detection of maternal DNA in umbilical cord blood by polymerase chain reaction amplification of minisatellite sequences

Briz

Regidor

Monteagudo

et al. 1998

Bone Marrow Transplant

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Summary:One of the concerns about the use of cord blood as a source of hematopoietic stem cells for allogeneic transplantation is the possibility of contamination by maternal cells which could cause life-threatening GVHD. We have assessed cord blood contamination using PCR analysis of several minisatellite regions to detect maternal DNA. Eighty mother-cord pairs were obtained for this study. In one case there were no specific maternal alleles at any loci and, therefore, cord blood could not be evaluated. Thus, there was a total of 79 informative cases for the detection of maternal cells in the fetal circulation. In most cases, the level of detection was between 0.5 and 1%. We detected maternal DNA in the cord blood sample in only one case (1.26%), and the analysis of dilution experiments led to an estimate of 0.5-1% maternal cells. In conclusion, using PCR amplification of hypervariable regions, maternal DNA is very rarely detected in the cord blood collected at birth, although this approach has a relatively low level of sensitivity. Keywords: cord blood; maternal cell contamination; hematopoietic stem cell transplantation; minisatellite repeats; polymerase chain reaction Umbilical cord blood contains hematopoietic progenitor cells 1 that can be used as an acceptable alternative to bone marrow for clinical transplantation. 2 Although initial donors were siblings, more recently cord blood transplants from unrelated donors have been used, and international umbilical cord blood banks have already been established in Europe and in the USA.One of the remaining concerns about the use of cord blood in unrelated transplantation is the possibility of contamination by maternal cells; maternal T lymphocytes only partially matched with the histocompatibility antigens of the recipient could cause life-threatening GVHD after transplantation.The objective of this study was to determine the frequency and degree of cord blood contamination by Correspondence: Dr M Briz, Hospital Puerta de Hierro, San Martín de Porres 4, 28035-Madrid, Spain Received 4 November 1997; accepted 3 January 1998 maternal cells; we used polymerase chain reaction (PCR) amplification of highly polymorphic DNA regions (minisatellite sequences) to detect maternal DNA. Materials and methodsPregnant women were recruited before delivery at Móstoles Hospital (Department of Obstetrics and Gynecology). Samples were collected after full-term vaginal delivery from women who had experienced no complications during pregnancy or at the time of delivery. Informed consent was obtained in all cases. Collection of maternal and umbilical cord samplesCord blood was collected during the third stage of labor, before delivery of the placenta. Briefly, the umbilical cord was double-clamped and cut; after removal of the newborn, the umbilical vein of the cord was punctured aseptically and the blood was collected in a standard plastic blood donation bag containing CPD as anticoagulant. To minimize maternal cell contamination, we collected cord blood by gravity in a closed system, ...

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Placental Blood as a Source of Hematopoietic Stem Cells for Transplantation into Unrelated Recipients

Abstract: HLA-mismatched placental blood from unrelated donors is an alternative source of stem cells for hematopoietic reconstitution in children.

Cited by 989 publications

References 31 publications

Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

Umbilical cord blood banking: an update

Detection of maternal DNA in umbilical cord blood by polymerase chain reaction amplification of minisatellite sequences

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