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Comparison of survival after transplantation of double unit UCBT with that of adult donors. Better understanding of how to overcome the limitations of UCBT, such as delayed engraftment and poor immune cell reconstitution, is necessary to expand the indications of UCBT. A number of options are under laboratory and clinical assessment. One strategy would be to use perfusion of the placenta to collect more cells at the birth of a baby.
Multiple investigators have explored UCB expansion strategies as a way to augment the low cell dose. Delaney et al, 77 using the notch ligand Delta-1, demonstrated expansion of short-term repopulating cells and an improvement in the time of neutrophil engraftment to 16 days. Other preclinical efforts to ex vivo expand HSCs have been reported. Other means to enhance the efficacy of UCBT are to increase the homing to and nurturing of cells within the hematopoietic microenvironment.
Recent efforts include experimental studies using fucosylation of cells, inhibition of Dipeptidylpeptidase 4 DPP4, expressed as CD26 on the cell surface , and pretreatment of donor cells with a modified Prostaglandin PG E molecule. Combinations of these procedures may result in greater improvement in engraftment capacity than any one procedure itself.
An example of a potential combination treatment is that of either PGE, cell fucosylation, or DPP4 inhibitor treatment of donor cells followed by the infusion of these cells into conditioned recipients that are given orally active DPP4 inhibitor prior to and following the UCB cell graft. As we learn more about the biology of HSCs and their responses to cytokines and cells of the hematopoietic microenvironment and as we determine how best to provide effective manipulation of these events, UCBT may become a more efficient and efficacious procedure. The field of UCBT has matured considerably over the last 25 years since the initial laboratory studies in Indiana and clinical work in Paris.
UCBT in children has similar or superior survival to a standard transplant, and results for adults continue to improve. Randomized studies to compare graft sources are underway. This is an evolving field that must be carefully evaluated with more comparative studies, which can be achieved by multicenter collaborations. UCBT needs to meet several new challenges. Delays in immune reconstitution have led to an increased incidence of late viral infections, which can be fatal, after UCBT. Lymphocyte subsets, Natural Killer cells, or mesenchymal stromal cells from UCB could be isolated and cultured and used for immunotherapy or cell repair.
There are concerns with the use of iPS or other cell types for future regenerative medicine attempts, but should these cells be obtained from UCB cells and be shown to be safe and effective as treatment modalities, it is likely that UCB will have enhanced usefulness. When we look back after the next 25 years, we anticipate an abundant UCB supply, digitalized UCB selection, multiple new indications, and significantly improved clinical outcomes. The remaining author declares no competing financial interests.
National Center for Biotechnology Information , U. Prepublished online May Ballen , 1 Eliane Gluckman , 2 and Hal E. Author information Article notes Copyright and License information Disclaimer. Received Feb 8; Accepted May 6. This article has been cited by other articles in PMC.
Abstract Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. The first cord blood transplant The first UCBT, performed in October , was made possible by an international collaboration between Arleen Auerbach from the Rockefeller University in New York, who described a method of prenatal diagnosis in FA, 17 Broxmeyer from IUSM, and Gluckman from the Hospital Saint Louis in Paris, who demonstrated that the in vivo hypersensitivity of FA cells caused increased toxicity in the pretransplant conditioning regimen used in aplastic anemia 18 and who was the first to use modified, attenuated, dose conditioning in these patients to improve short- and long-term survival.
Open in a separate window. Comparison of graft sources: Table 1 Selected series comparing myeloablative single unit UCBT with transplantation of adult donors in adults. Future directions and the scientific basis of HSC function revisited Better understanding of how to overcome the limitations of UCBT, such as delayed engraftment and poor immune cell reconstitution, is necessary to expand the indications of UCBT. Conclusions The field of UCBT has matured considerably over the last 25 years since the initial laboratory studies in Indiana and clinical work in Paris.
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Results of a phase 1 trial using the AastromReplicell System. Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine. Filippo Milano Fred Hutch file Click for high-res version. Colleen Delaney Fred Hutch file Click for high-res version. We are committed to cultivating a workplace in which diverse perspectives and experiences are welcomed and respected.
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