Mesenchymal stem cells protect retinal ganglion cells from degeneration via mitochondrial donation

JIANG, D.; Feng, H.; Zhang, Z.; Yan, B.; Chen, L.; Ma, C.; Li, C.; Han, S.; Zhang, Y.; Chen, P.; Tse, H.-F.; Fu, Q.; Chiu, K.; Lian, Q.

doi:10.1101/393959

bioRxiv · 10.1101/393959

Mesenchymal stem cells protect retinal ganglion cells from degeneration via mitochondrial donation

JIANG, D.·Feng, H.·Zhang, Z.·Yan, B.·Chen, L.·Ma, C.·Li, C.·Han, S.·Zhang, Y.·Chen, P.·Tse, H.-F.·Fu, Q.·Chiu, K.·Lian, Q.

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Abstract

Retinal ganglion cell (RGC) degeneration is extremely hard to repair or regenerate and is often coupled with mitochondrial dysfunction. Mesenchymal stem cells (MSCs)-based treatment has been demonstrated beneficial for RGC against degeneration. However, underlying mechanisms of MSC-provided RGC protection are largely unknown other than neuropectective paracrine actions. In this study, we sought to investigate whether mitochondrial donation can preserve RGC functions, in a mitochondrial Ndufs4 deficient mouse model of RGC degeneration. The results revealed intravitreal transplanted by induced pluripotent stem cell derived-MSCs (iPSC-MSC) could donate their mitochondria through crossing inner limited membrane to host RGCs. Furthermore, the donated mitochondria effectively protected against RGC death and largely preserved retinal function in Ndufs4-KO mice. Importantly, the protective effects of mitochondrial donation from MSCs were associated with management of pro-inflammatory cytokines. Our data identified a novel role of MSCs-mitochondrial donation in protection of RGC from degeneration, and highlight a viable therapeutic strategy by manipulating stem cell mitochondrial donation for the treatment of retina degeneration in future.

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JIANG, D., Feng, H., Zhang, Z., Yan, B., Chen, L., Ma, C., Li, C., Han, S., Zhang, Y., Chen, P., Tse, H.-F., Fu, Q., Chiu, K., Lian, Q.. 2018-08-19. Mesenchymal stem cells protect retinal ganglion cells from degeneration via mitochondrial donation. https://doi.org/10.1101/393959

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