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

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-ter...

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Published inScience translational medicine Vol. 9; no. 414
Main Authors Radtke, Stefan, Adair, Jennifer E, Giese, Morgan A, Chan, Yan-Yi, Norgaard, Zachary K, Enstrom, Mark, Haworth, Kevin G, Schefter, Lauren E, Kiem, Hans-Peter
Format Journal Article
LanguageEnglish
Published United States 01.11.2017
Subjects
Animals
Antigens, CD - metabolism
Blood Platelets - cytology
Cell Lineage
Clone Cells
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - cytology
Humans
Macaca nemestrina
Neutrophils - cytology
Phenotype
Transcriptome - genetics
Transplantation, Autologous
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Summary: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.
ISSN:1946-6242
DOI:10.1126/scitranslmed.aan1145