Immune Responses to Human Induced Pluripotent Stem Cells and their Derived Myogenic Progenitors Are Mediated by Different Mechanisms in Humanized Mice

Benabdallah, B.; Desaulniers-Langevin, C.; Goyer, M.-L.; Colas, C.; Maltais, C.; Li, Y.; Guimond, J. V.; Tremblay, J. P.; Haddad, E.; Beausejour, C.

doi:10.1101/550699

bioRxiv · 10.1101/550699

Immune Responses to Human Induced Pluripotent Stem Cells and their Derived Myogenic Progenitors Are Mediated by Different Mechanisms in Humanized Mice

Benabdallah, B.·Desaulniers-Langevin, C.·Goyer, M.-L.·Colas, C.·Maltais, C.·Li, Y.·Guimond, J. V.·Tremblay, J. P.·Haddad, E.·Beausejour, C.

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Abstract

It is still unclear if immune responses will compromise the large scale utilization of cell therapies derived from human induced pluripotent stem cells (hiPSCs). To answer this question, we used humanized mouse models and evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or 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 teratoma if using partially differentiated autologous human cells. HighlightsO_LIhiPSC-derived myofibers are tolerated in autologous humanized mouse models C_LIO_LIInfiltration of autologous T cells is not predictive of successful skeletal muscle engraftment C_LIO_LIAdoptive transfer of NK cells prevents the formation of hiPSCs derived teratomas C_LIO_LINK cells are unable to reject established teratomas C_LI

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Benabdallah, B., Desaulniers-Langevin, C., Goyer, M.-L., Colas, C., Maltais, C., Li, Y., Guimond, J. V., Tremblay, J. P., Haddad, E., Beausejour, C.. 2019-02-15. Immune Responses to Human Induced Pluripotent Stem Cells and their Derived Myogenic Progenitors Are Mediated by Different Mechanisms in Humanized Mice. https://doi.org/10.1101/550699

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