Organoid-derived C-Kit+/SSEA4− human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents
Organoid-derived C-Kit+/SSEA4− human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents
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DOI：
10.1038/s41467-019-08961-0
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发表时间：
2019-03
影响因子：
16.6
通讯作者：
T. Zou;Lixiong Gao;Yuxiao Zeng;Qiyou Li;Yijian Li;Siyu Chen;Xisu Hu;Xi Chen;C. Fu;Haiwei Xu
中科院分区：
文献类型：
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作者：
T. Zou;Lixiong Gao;Yuxiao Zeng;Qiyou Li;Yijian Li;Siyu Chen;Xisu Hu;Xi Chen;C. Fu;Haiwei Xu
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.
