Protocols for Hematopoietic Stem Cell Expansion from Umbilical Cord Blood

Abstract

The reconstitution of adult stem cells may be a promising source for the regeneration of damaged tissues and for the reconstitution of organ dysfunction. However, there are two major limitations to the use of such cells: they are rare, and only a few types exist that can easily be isolated without harming the patient. The best studied and most widely used stem cells are of the hematopoietic lineage. Pioneering work on hematopoietic stem cell (HSC) transplantation was done in the early 1970s by ED. Thomas and colleagues. Since then HSCs have been used in allogenic and autologous transplantation settings to reconstitute blood formation after high-dose chemotherapy for various blood disorders. The cells can be easily harvested from donors, but the cell number is limited, especially when the HSCs originate from umbilical cord blood (UCB). It would be desirable to set up an ex vivo strategy to expand HSCs in order to overcome the cell dose limit, whereby the expansion would favor cell proliferation over cell differentiation. This review provides an overview of the various existing HSC expansion strategies-focusing particularly on stem cells derived from UCB-of the parameters that might affect the outcome, and of the difficulties that may occur when trying to expand such cells.

Going straight to the point: intra-BM injection of hematopoietic progenitors

“…[19][20][21] However, the utilization of UCB for transplantation of larger patients has been impeded by the limited nucleated cell dose available from individual UCB units. [22][23][24] To overcome the cell dose limitation, investigators have been studying strategies such as ex vivo expansion, 25,26 administration of multiple unit UCB units [27][28][29][30] and treating the graft with agents that potentially enhance homing to the marrow niche. 31,32 In view of the limited cell availability in UCB grafts, nonspecific loss of progenitors is of particular importance and has prompted investigators to study the injection of UCB grafts directly into the BM space to improve engraftment.…”

Human Umbilical Cord Blood Stem Cells Rescue Ischemic Tissues

“…Current expansion methods cannot make up for the cells lost in the storage process, let alone augment them to a suitable dosing regimen (Hows et al, 1992;Liu et al, 2006;Traycoff et al, 1995;Yao et al, 2006). However, in the last couple of years, there have been several studies looking at ways to maximize yield, storage and recovery, and expansion which require validation (Gonzalez et al, 2010;Koestenbauer et al, 2009;Lin et al, 2010;Song et al, 2010;Vanneaux et al, 2010;Zeisburger et al, 2010). Third, the cause of limited graft survival in the recipient remains to be determined even though the paradigm of underlying mechanisms on the functional improvement after stem cell transplantation has been changed from cell replacement to a paracrine bystander effect.…”

Bioreactor for Blood Product Production

“…We believe this work comes (13,19). While achieving extensive true HSPC represents an important step towards Blood Pharming by self-renewal in vitro has proven exceedingly challengachieving both an increase in cell densities and a reducing, and transplant trials based on the provision of these tion in protein consumption.…”