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

Science Translational Medicine
Stefan RadtkeHans-Peter Kiem

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+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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Citations

Nov 14, 2018·The Journal of Clinical Investigation·Hongjie WangAndré Lieber
Jun 15, 2019·Annals of the New York Academy of Sciences·Luena PapaRonald Hoffman
Jul 23, 2019·International Journal of Radiation Biology·Laura M CalviJames Palis
Apr 10, 2020·Blood·Stefan Radtke, Hans-Peter Kiem
Jun 9, 2020·British Journal of Haematology·Olivier HumbertHans-Peter Kiem
Oct 19, 2019·Nature Biomedical Engineering·Daniel E Bauer
Nov 21, 2020·British Journal of Haematology·Stefan CordesCynthia E Dunbar
Dec 19, 2020·British Journal of Haematology·Thomas A Fox, Claire Booth
Mar 1, 2018·Current Stem Cell Reports·Sunil S Raikar, H Trent Spencer
Oct 21, 2020·Molecular and Cellular Biology·Vigneshwaran VenkatesanSaravanabhavan Thangavel
Aug 18, 2020·Molecular Therapy. Methods & Clinical Development·Stefan RadtkeHans-Peter Kiem
Apr 1, 2021·Stem Cell Reviews and Reports·Karthik V KaruppusamySaravanabhavan Thangavel
May 28, 2021·Gene Therapy·Pervinder Sagoo, H Bobby Gaspar
May 2, 2020·Molecular Therapy. Methods & Clinical Development·Jennifer E AdairHans-Peter Kiem

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