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

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.

• Authors: 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, Weiqiang Li
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 5196 (10 15 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 33060592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, Platelet-Derived Growth Factor beta

Topics

• Animals
• Blood-Brain Barrier (metabolism)
• Brain Ischemia (metabolism, pathology)
• Cell Differentiation (genetics)
• Infarction, Middle Cerebral Artery
• Male
• Mice
• Mice, Inbred C57BL
• Neural Crest (metabolism)
• Pericytes (metabolism)
• Pluripotent Stem Cells (metabolism)
• Receptor, Platelet-Derived Growth Factor beta (metabolism)
• Recovery of Function (genetics, physiology)
• Stroke (metabolism, pathology)
• Transcriptome