Research ArticleStem Cells

A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates

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Science Translational Medicine  01 Nov 2017:
Vol. 9, Issue 414, eaan1145
DOI: 10.1126/scitranslmed.aan1145

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Refining the gold standard

CD34-positive hematopoietic cells are the gold standard for stem cell therapy and transplantation of stem cell–enriched grafts. However, most of the cells within this population will not contribute to engraftment. Using a robust nonhuman primate transplantation model, Radtke et al. identified a stem cell–enriched subpopulation of CD34-positive cells that was exclusively responsible for multilineage engraftment. The cell dose of this subpopulation correlated with neutrophil and platelet recovery and reliably predicted overall transplant success. The authors observed phenotypic and transcriptomic similarities between these cells and human hematopoietic cells with high engraftment and repopulating potential. These data suggest a refined subpopulation of CD34-positive cells for use in transplantation and gene therapy/editing approaches.

Abstract

Hematopoietic reconstitution after bone marrow transplantation is thought to be driven by committed multipotent progenitor cells followed by long-term engrafting hematopoietic stem cells (HSCs). We observed a population of early-engrafting cells displaying HSC-like behavior, which persisted long-term in vivo in an autologous myeloablative transplant model in nonhuman primates. To identify this population, we characterized the phenotype and function of defined nonhuman primate hematopoietic stem and progenitor cell (HSPC) subsets and compared these to human HSPCs. We demonstrated that the CD34+CD45RACD90+ cell phenotype is highly enriched for HSCs. This population fully supported rapid short-term recovery and robust multilineage hematopoiesis in the nonhuman primate transplant model and quantitatively predicted transplant success and time to neutrophil and platelet recovery. Application of this cell population has potential in the setting of HSC transplantation and gene therapy/editing approaches.

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