Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia

Kang, Hyoung Jin; Lee, J W; Kim, H; Shin, Hee Young; Ahn, Hyo Seop

doi:10.1038/bmt.2009.247

Cited by 9 publications

(5 citation statements)

References 10 publications

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“…Unfortunately despite these attractive features, cord blood transplantations for adult patients still lag behind due to a low number of nucleated cells and CD34 + cells within a single cord blood collection. Double cord transplantation and a combined infusion of an unmanipulated and an expanded graft have been tried in clinics to tackle this problem [2] , [3] , [4] , [5] . Thus the strategies to expand either CD34 + cells or the selected subpopulations from cord blood are an area of active research.…”

Section: Introductionmentioning

confidence: 99%

Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

Kale

Limaye

2010

PLoS ONE

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BackgroundCord blood (CB) is a promising source for hematopoietic stem cell transplantations. The limitation of cell dose associated with this source has prompted the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). However, the expansion procedure is known to exhaust the stem cell pool causing cellular defects that promote apoptosis and disrupt homing to the bone marrow. The role of apoptotic machinery in the regulation of stem cell compartment has been speculated in mouse hematopoietic and embryonic systems. We have consistently observed an increase in apoptosis in the cord blood derived CD34+ cells cultured with cytokines compared to their freshly isolated counterpart. The present study was undertaken to assess whether pharmacological inhibition of apoptosis could improve the outcome of expansion.Methodology/Principal FindingsCB CD34+ cells were expanded with cytokines in the presence or absence of cell permeable inhibitors of caspases and calpains; zVADfmk and zLLYfmk respectively. A novel role of apoptotic protease inhibitors was observed in increasing the CD34+ cell content of the graft during ex vivo expansion. This was further reflected in improved in vitro functional aspects of the HSPCs; a higher clonogenicity and long term culture initiating potential. These cells sustained superior long term engraftment and an efficient regeneration of major lympho-myeloid lineages in the bone marrow of NOD/SCID mouse compared to the cells expanded with growth factors alone.Conclusion/SignificanceOur data show that, use of either zVADfmk or zLLYfmk in the culture medium improves expansion of CD34+ cells. The strategy protects stem cell pool and committed progenitors, and improves their in vitro functionality and in vivo engraftment. This observation may complement the existing protocols used in the manipulation of hematopoietic cells for therapeutic purposes. These findings may have an impact in the CB transplant procedures involving a combined infusion of unmanipulated and expanded grafts.

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Section: Introductionmentioning

confidence: 99%

Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

Kale

Limaye

2010

PLoS ONE

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“…In 2005, the group reported the results achieved in the first 23 recipients treated with double UCB transplants 20,21. Since then, other groups have confirmed the efficacy of this technique 22,23…”

Section: Contextmentioning

confidence: 99%

Umbilical cord blood banking: from personal donation to international public registries to global bioeconomy

Petrini¹

2014

JBM

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The procedures for collecting voluntarily and freely donated umbilical cord blood (UCB) units and processing them for use in transplants are extremely costly, and the capital flows thus generated form part of an increasingly pervasive global bioeconomy. To place the issue in perspective, this article first examines the different types of UCB biobank, the organization of international registries of public UCB biobanks, the optimal size of national inventories, and the possibility of obtaining commercial products from donated units. The fees generally applied for the acquisition of UCB units for transplantation are then discussed, and some considerations are proposed regarding the social and ethical implications raised by the international network for the importation and exportation of UCB, with a particular emphasis on the globalized bioeconomy of UCB and its commerciality or lack thereof.

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“…In 2005, a team led by John Wagner published satisfactory results achieved in 23 recipients who received double partially human leukocyte antigen (HLA)-matched UCB units [ 26 , 27 ]. Since then, this technique has been demonstrably efficient as a simple approach for overcoming cell dose limitations in older or heavier patients, in whom UCB transplantation with cell doses below this threshold is associated with slow hematopoietic recovery, poor engraftment, and high transplantation-related mortality [ 28 , 29 ].…”

Section: Umbilical Cord Blood Collection Processing and Cryopreservmentioning

confidence: 99%

The role and potential of umbilical cord blood in an era of new therapies: a review

et al. 2015

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In light of pioneering findings in the 1980s and an estimation of more than 130 million global annual births, umbilical cord blood (UCB) is considered to be the most plentiful reservoir of cells and to have regenerative potential for many clinical applications. Although UCB is used mainly against blood disorders, the spectrum of diseases for which it provides effective therapy has been expanded to include non-hematopoietic conditions; UCB has also been used as source for regenerative cell therapy and immune modulation. Thus, collection and banking of UCB-derived cells have become a popular option. However, there are questions regarding the cost versus the benefits of UCB banking, and it also raises complex ethical and legal issues. This review discusses many issues surrounding the conservation of UCB-derived cells and the great potential and current clinical applications of UCB in an era of new therapies. In particular, we describe the practical issues inherent in UCB collection, processing, and long-term storage as well as the different types of ‘stem’ or progenitor cells circulating in UCB and their uses in multiple clinical settings. Given these considerations, the trend toward UCB will continue to provide growing assistance to health care worldwide.

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Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia

Cited by 9 publications

References 10 publications

Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

Umbilical cord blood banking: from personal donation to international public registries to global bioeconomy

The role and potential of umbilical cord blood in an era of new therapies: a review

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