Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 9, Issue 414, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aan1145
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Funding
- NIH [HL115128, HL098489, AI096111]
- Fred Hutchinson Cancer Research Center
- Cuyamaca Foundation
- Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research
- Fred Hutchinson Cancer Research Center Endowed Chair for Cell and Gene Therapy
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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(+) CD45RA(-)CD90(+) 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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