Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice

Jiaqi Sun, Yinong Huang, Jin Gong, Jiancheng Wang, Yubao Fan, Jianye Cai, Yi Wang, Yuan Qiu, Yili Wei, Chuanfeng Xiong, Jierui Chen, Bin Wang, Yuanchen Ma, Lihua Huang, Xiaoyong Chen, Shuwei Zheng, Weijun Huang, Qiong Ke, Tao Wang, Xiaoping Li, Wei Zhang, Andy Peng Xiang () and Weiqiang Li ()
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Jiaqi Sun: The Third Affiliated Hospital, Sun Yat-Sen University
Yinong Huang: The Third Affiliated Hospital, Sun Yat-Sen University
Jin Gong: The Third Affiliated Hospital, Sun Yat-Sen University
Jiancheng Wang: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Yubao Fan: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Jianye Cai: The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University
Yi Wang: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Yuan Qiu: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Yili Wei: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Chuanfeng Xiong: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Jierui Chen: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Bin Wang: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Yuanchen Ma: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Lihua Huang: Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
Xiaoyong Chen: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Shuwei Zheng: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Weijun Huang: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Qiong Ke: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Tao Wang: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Xiaoping Li: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Wei Zhang: Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Department of Neurosurgery, The First Affiliated Hospital of Guangdong Pharmaceutics University
Andy Peng Xiang: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University
Weiqiang Li: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: Abstract Pericytes play essential roles in blood–brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRβ, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.

Date: 2020
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DOI: 10.1038/s41467-020-19042-y

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