Organoid-derived C-Kit+/SSEA4− human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents

• Published in: Nature communications Vol. 10; no. 1; pp. 1205 - 17
• Main Authors: Zou, Ting, Gao, Lixiong, Zeng, Yuxiao, Li, Qiyou, Li, Yijian, Chen, Siyu, Hu, Xisu, Chen, Xi, Fu, Caiyun, Xu, Haiwei, Yin, Zheng Qin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.03.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/31; 38/39; 38/77; 45/100; 631/378/1689/364; 631/532/2117; 64/60; 64/86; 692/308/2171; 692/308/2778; 692/308/575; 82/51; Animal models; Animals; c-Kit protein; Cell Differentiation - physiology; Cell Line; Cell Separation; Cell surface; Cell Survival; Cells (biology); Coculture Techniques; Degeneration; Disease Models, Animal; Female; Flow Cytometry; Gene Expression Profiling; Gliosis; Human Embryonic Stem Cells - metabolism; Humanities and Social Sciences; Humans; Inflammation; Male; Mice; Mice, SCID; Microglia; multidisciplinary; Neural stem cells; Organoids; Organoids - cytology; Organoids - metabolism; Photoreception; Photoreceptor Cells - metabolism; Photoreceptor Cells - transplantation; Photoreceptors; Progenitor cells; Proto-Oncogene Proteins c-kit - metabolism; Rats; Regeneration; Retina; Retinal degeneration; Retinal Degeneration - therapy; Rodents; Science; Science (multidisciplinary); Stage-Specific Embryonic Antigens - metabolism; Stem cell transplantation; Stem Cell Transplantation - methods; Stem cells; Surface markers; Transplantation; Treatment Outcome
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08961-0

Stem cell therapy may replace lost photoreceptors and preserve residual photoreceptors during retinal degeneration (RD). Unfortunately, the degenerative microenvironment compromises the fate of grafted cells, demanding supplementary strategies for microenvironment regulation. Donor cells with both proper regeneration capability and intrinsic ability to improve microenvironment are highly desired. Here, we use cell surface markers (C-Kit + /SSEA4 − ) to effectively eliminate tumorigenic embryonic cells and enrich retinal progenitor cells (RPCs) from human embryonic stem cell (hESC)-derived retinal organoids, which, following subretinal transplantation into RD models of rats and mice, significantly improve vision and preserve the retinal structure. We characterize the pattern of integration and materials transfer following transplantation, which likely contribute to the rescued photoreceptors. Moreover, C-Kit + /SSEA4 − cells suppress microglial activation, gliosis and the production of inflammatory mediators, thereby providing a healthier host microenvironment for the grafted cells and delaying RD. Therefore, C-Kit + /SSEA4 − cells from hESC-derived retinal organoids are a promising therapeutic cell source. Stem cell transplantation to treat retinal degeneration could be limited by the degenerative microenvironment. Here, the authors show that C-Kit + /SSEA4 –  progenitor cells enriched from human embryonic stem cell derived retinal organoids protect retinal structure, suppress microglial activation, gliosis and inflammation.