Research Paper Volume 12, Issue 7 pp 6306—6323
Bone marrow mesenchymal stem cells transplantation alleviates brain injury after intracerebral hemorrhage in mice through the Hippo signaling pathway
- 1 Department of Neurosurgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
- 2 Department of Neurology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China
- 3 School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China
- 4 Department of Neurosurgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Received: December 13, 2019 Accepted: March 2, 2020 Published: April 9, 2020
https://doi.org/10.18632/aging.103025How to Cite
Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Intracerebral hemorrhage (ICH) is a common acute nervous system disease with high mortality and severe disability. Mesenchymal stem cells (MSCs) have been reported to promote neurogenesis and to alleviate side effects in areas of brain injury areas. The Hippo pathway regulates diverse cellular processes, including cell survival, proliferation, differentiation, and organ size. Here, we found that transplantation of bone marrow MSCs (BM-MSCs) into the brains of mice could alleviate ICH-mediated injury and protect astrocytes from apoptosis by regulating mammalian sterile 20-like kinase (MST)1 and Yes-associated protein (YAP). Knocking down of MST1 by si-RNA triggered YAP nuclear translocation. We further demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and become capable of proliferating after BM-MSC transplantation via the Hippo signaling pathway. Together, our identification of the Hippo pathway in mediating the beneficial effects of BM-MSCs may provide a novel therapeutic target in the treatment and management of ICH.