Human Pluripotent Stem Cells Derived Endothelial Cells Repair Choroidal Ischemia

Author:

Li Mengda123ORCID,Wang Peiliang456ORCID,Huo Si Tong123ORCID,Qiu Hui4567ORCID,Li Chendi123,Lin Siyong123,Guo Libin123,Ji Yicong123,Zhu Yonglin6ORCID,Liu Jinyang456ORCID,Guo Jianying8ORCID,Na Jie456ORCID,Hu Yuntao123ORCID

Affiliation:

1. Eye Center Beijing Tsinghua Changgung Hospital Beijing 102218 China

2. Institute for Precision Medicine Tsinghua University Beijing 100084 China

3. School of Clinical Medicine Tsinghua University Beijing 100084 China

4. SXMU‐Tsinghua Collaborative Innovation Center for Frontier Medicine School of Medicine Tsinghua University Beijing 100084 China

5. State Key Laboratory for Complex, Severe, and Rare Diseases Tsinghua University Beijing 100084 China

6. Center for Stem Cell Biology and Regenerative Medicine School of Medicine Tsinghua University Beijing 100084 China

7. School of Life Sciences Tsinghua University Beijing 100084 China

8. Center for Reproductive Medicine Department of Obstetrics and Gynaecology Peking University Third Hospital Beijing 100191 China

Abstract

AbstractChoroidal atrophy is a common fundus pathological change closely related to the development of age‐related macular degeneration (AMD), retinitis pigmentosa, and pathological myopia. Studies suggest that choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first cells lost in choroidal atrophy. It is found that endothelial cells derived from human pluripotent stem cells (hPSC‐ECs) through the MESP1+ mesodermal progenitor stage express CECs‐specific markers and can integrate into choriocapillaris. Single‐cell RNA‐seq (scRNA‐seq) studies show that hPSC‐ECs upregulate angiogenesis and immune‐modulatory and neural protective genes after interacting with ex vivo ischemic choroid. In a rat model of choroidal ischemia (CI), transplantation of hPSC‐ECs into the suprachoroidal space increases choroid thickness and vasculature density. Close‐up examination shows that engrafted hPSC‐ECs integrate with all layers of rat choroidal vessels and last 90 days. Remarkably, EC transplantation improves the visual function of CI rats. The work demonstrates that hPSC‐ECs can be used to repair choroidal ischemia in the animal model, which may lead to a new therapy to alleviate choroidal atrophy implicated in dry AMD, pathological myopia, and other ocular diseases.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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