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Nat Commun. 2019 Mar 14;10(1):1205. doi: 10.1038/s41467-019-08961-0.

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

Zou T1,2, Gao L1,2, Zeng Y1,2, Li Q1,2, Li Y1,2, Chen S1,2, Hu X1,2, Chen X1,2, Fu C1,2, Xu H3,4, Yin ZQ5,6.

Author information

1
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
2
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.
3
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. xuhaiwei@tmmu.edu.cn.
4
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China. xuhaiwei@tmmu.edu.cn.
5
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. qinzyin@aliyun.com.
6
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China. qinzyin@aliyun.com.

Abstract

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.

PMID:
30872578
PMCID:
PMC6418223
DOI:
10.1038/s41467-019-08961-0
[Indexed for MEDLINE]
Free PMC Article

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