Organoid-derived C-Kit + /SSEA4 − human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents
Ting Zou,Lixiong Gao,Yuxiao Zeng,Qiyou Li,Yijian Li,Siyu Chen,Xisu Hu,Xi Chen,Caiyun Fu,Haiwei Xu,Zheng Qin Yin +10 more
TL;DR: It is shown that C-Kit+/SSEA4– progenitor cells enriched from human embryonic stem cell derived retinal organoids protect retinal structure, suppress microglial activation, gliosis and inflammation, and provide a healthier host microenvironment for the grafted cells and delaying RD.
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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.
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Citations
•Journal Article
Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa
TL;DR: In this paper, the role of microglia as a contributor to photoreceptor degeneration in the rd10 mouse model of retinitis pigmentosa (RP) was explored.
134
A look into retinal organoids: methods, analytical techniques, and applications.
Tess A. V. Afanasyeva,Julio C. Corral-Serrano,Alejandro Garanto,Alejandro Garanto,Ronald Roepman,Michael E. Cheetham,Rob W.J. Collin +6 more
TL;DR: The 3D iPSC-derived retina-like tissue called retinal organoid as discussed by the authors contains all major retina-specific cell types: amacrine, bipolar, horizontal, retinal ganglion cells, Muller glia, as well as rod and cone photoreceptors.
A phase I clinical trial of human embryonic stem cell-derived retinal pigment epithelial cells for early-stage Stargardt macular degeneration: 5-years' follow-up.
Shiying Li,Yong Liu,Lei Wang,Fang Wang,Tong-Tao Zhao,Qiyou Li,Haiwei Xu,Xiaohong Meng,Jie Hao,Qi Zhou,Liu Wang,Zheng-Qin Yin +11 more
TL;DR: In this article, a prospective clinical study was conducted to evaluate the long-term biosafety and efficacy of transplantation of human embryonic stem cells-derived retinal pigment epithelial (hESC-RPE) cells in early stage of Stargardt macular degeneration (STGD1).
50
Role of the Internal Limiting Membrane in Structural Engraftment and Topographic Spacing of Transplanted Human Stem Cell-Derived Retinal Ganglion Cells.
Kevin Y. Zhang,Caitlyn Tuffy,Joseph L. Mertz,Sarah Quillen,Laurence Wechsler,Harry A. Quigley,Donald J. Zack,Thomas V. Johnson +7 more
TL;DR: In this article, the cellular permeability of the internal limiting membrane (ILM) was increased for retinal ganglion cell (RGC) transplantation, and extracellular matrix digestion using proteolytic enzymes achieved ILM disruption while minimizing retinal toxicity and preserving glial reactivity.
46
Advanced human developmental toxicity and teratogenicity assessment using human organoid models.
TL;DR: A recent review as mentioned in this paper discusses the recent advances in the use of human organoid models for developmental toxicity and teratogenicity assessment of distinct tissues/organs following exposure to pharmaceutical compounds, heavy metals, persistent organic pollutants, nanomaterials, and ambient air pollutants.
45
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