iv. In vivo expansion of cord blood stem cells

A. Hematopoietic recovery after unrelated umbilical cord-blood allogeneic transplantation in adults treated with in vivo stem cell factor (R-MetHuSCF) and filgrastim administration. Wadhwa,P.D.; Lazarus,H.M.; Koc,O.N.; Jaroscak,J.; Woo,D.; Stevens,C.E.; Rubinstein,P.; Laughlin,M.J. Leuk.Res. 2003;27:215-220

Transplantation with unrelated umbilical cord blood (UCB) is marked by delayed hematologic recovery. This report summarizes two adults with chronic myelogenous leukemia (CML), who received myeloablative conditioning followed by infusion of a non-expanded single UCB graft. These CML patients were enrolled in a clinical trial incorporating concomitant in vivo administration of stem cell factor (R-MetHuSCF) and filgrastim from day of UCB infusion until attained hematopoietic recovery. Each patient engrafted fully with donor UCB, with days to absolute neutrophil count >500/L being 13 and 29 days, respectively. Both patients remain in cytogenetic remission at 28 months follow-up. 'In vivo UCB expansion' with administration of concomitant R-MetHuSCF and filgrastim may facilitate prompt hematologic engraftment.

B. Thrombopoietin expands hematopoietic stem cells after transplantation. Fox N, Priestley G, Papayannopoulou T, Kaushansky K. J Clin Invest 2002; 110:389-394.

Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, the authors transplanted normal marrow cells into lethally irradiated Tpo (-/-) and Tpo(+/+) mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. To assess whether long-term repopulating (LTR) HSCs self-renew and expand in Tpo(-/-) recipients or controls, they performed limiting-dilution secondary transplants using donor cells from the Tpo(-/-) or Tpo(+/+) recipients 5-7.5 weeks following primary transplantation. The results indicated that LTR HSCs expand to levels 10-20 times greater within this time period in normal recipients than in Tpo-null mice and that physiologically relevant amounts of TPO administered to the Tpo(-/-) recipients could substantially correct this defect. The authors concluded that TPO greatly promotes the self-renewal and expansion of HSCs in vivo following marrow transplantation.