Jennifer L. Gori, K. L. Watts, Devikha Chandrasekaran
Nov 15, 2013
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Blood
Abstract
Chemical factors that simultaneously maintain and expand definitive hematopoietic stem cells (HSCs) have the potential to greatly improve the clinical outcome in patients transplanted with allogeneic umbilical cord blood or gene corrected autologous CD34+ cells, in which the number of cells available for transplantation is limited. The recently discovered small molecules UM729 and UM171 effectively expand HSCs and synergize with StemRegenin1 (SR1) to enhance human HSC expansion, leading to successful long-term engraftment of SCID repopulating cells (SRCs) in immunodeficient mice. In order to facilitate translation of these small molecules for clinical use, we sought to determine the effect of UM729 and UM171 on expansion and transduction of nonhuman primate CD34+ cells from various sources. We hypothesized that UM171 would expand definitive CD34+ HSCs from macaque umbilical cord blood (Mn UCB), thereby increasing the definitive HSC cell dose available for engraftment. Here, we compared engraftment of the progeny of 250,000 Mn UCB CD34+ cells after a 10-day expansion with cytokines with or without SR1, UM729, or UM171 in immunodeficient mice. Although all expansion conditions led to >44-fold increase in the number of CD34+ cells across all cohorts, mice transplanted with UM171 treated Mn UCB CD34+ cells had a significantly higher level of engraftment compared to all other groups (41% nonhuman primate CD45+ cells in peripheral blood at 10 weeks post transplantation, P Disclosures: No relevant conflicts of interest to declare.