Journal
BLOOD ADVANCES
Volume 6, Issue 18, Pages 5267-5278Publisher
ELSEVIER
DOI: 10.1182/bloodadvances.2022006984
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Funding
- NIH, National Heart, Lung, and Blood Institute [R01HL132891, U01HL134655]
- NIH, Office of the Director grant [P51 OD011106]
- [HHSN272200900037C]
- [OD010976]
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The administration of ex vivo expanded somatic myeloid progenitors is explored as a way to accelerate myeloid recovery. Recent studies have shown the potential of hematopoietic progenitors derived from MHC homozygous iPSCs in treating cytopenia with good tolerance and safety in experimental animals.
Administration of ex vivo expanded somatic myeloid progenitors has been explored as a way to facilitate a more rapid myeloid recovery and improve overall survival after myeloablation. Recent advances in induced pluripotent stem cell (iPSC) technologies have created alternative platforms for supplying off-the-shelf immunologically compatible myeloid progenitors, including cellular products derived from major histocompatibility complex (MHC) homozygous superdonors, potentially increasing the availability of MHC-matching cells and maximizing the utility of stem cell banking. However, the teratogenic and tumorigenic potential of iPSC-derived progenitor cells and whether they will induce alloreactive antibodies upon transfer remain unclear. We evaluated the safety and efficacy of using CD34+CD45+ hematopoietic progenitors derived from MHC homozygous iPSCs (iHPs) to treat cytopenia after myeloablative hematopoietic stem cell (HSC) transplantation in a Mauritian cynomolgus macaque (MCM) nonhuman primate (NHP) model. We demonstrated that infusion of iHPs was well tolerated and safe, observing no teratomas or tumors in the MCMs up to 1 year after HSC transplantation and iHP infusion. Importantly, the iHPs also did not induce significant levels of alloantibodies in MHC-matched or-mismatched immunocompetent MCMs, even after increasing MHC expression on iHPs with interferon -g. These results support the feasibility of iHP use in the setting of myeloablation and suggest that iHP products pose a low risk of inducing alloreactive antibodies.
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