Immune Responses to Human Induced Pluripotent Stem Cells and their Derived Myogenic Progenitors Are Mediated by Different Mechanisms in Humanized Mice
2019
It is still unclear if immune responses will compromise the large scale utilization of
cell therapiesderived from human
induced pluripotent stem cells(hiPSCs). To answer this question, we used
humanized mousemodels and evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a
muscle biopsyor differentiated from hiPSCs or fibroblasts. Our results showed that while allogeneic grafts were rejected, engraftment of autologous cells was tolerated, indicating reprogramming and differentiation procedures are not immunogenic. We also demonstrated that hiPSC-derived myogenic progenitors, in opposition to hiPSCs, are not targeted by natural killer (NK) cells both in vitro and in vivo. Yet, adoptive transfer of NK cells can prevent the formation of hiPSC-derived
teratoma. Overall, our findings suggest that hiPSC-derived muscular therapies will be tolerated in presence of a competent human immune system and highlight the risk of forming a
teratomaif using partially differentiated autologous human cells.
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