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

Publication Type:

Journal Article

Source:

Science translational medicine, Volume 9, Issue 414 (2017)

Keywords:

Animals, Antigens, CD, Blood Platelets, Cell Lineage, Clone Cells, Flow Cytometry Core Facility, hematopoietic stem cell transplantation, Hematopoietic Stem Cells, Humans, Macaca nemestrina, Neutrophils, PHENOTYPE, transcriptome, Transplantation, Autologous

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 CD34CD45RACD90 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.