Bone marrow mesenchymal stem cells transplantation alleviates brain injury after intracerebral hemorrhage in mice through the Hippo signaling pathway.

Xiao Chen,Yuhao Sun,Huaibin Liang,Guoyuan Yang,Qingfang Sun,Liuguan Bian,Yong Yang,Zhiyu Xi,Can-Xin Xu,Jiaji Pan

doi:10.18632/aging.103025

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.

Highlights

Intracerebral hemorrhage (ICH), which is characterized by high mortality and disability, is the most severe form of stroke with no effective treatment modality, considerable progress has been made in animal and preclinical research [1, 2]
We further demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and become capable of proliferating after BM-Mesenchymal stem cells (MSCs) transplantation via the Hippo signaling pathway
bone marrow MSCs (BM-MSCs) transplantation led to a decrease in ICH hematoma volume on day 3 as compared with the phosphate buffered saline (PBS) group (p < 0.05) (Figure 1A)

Summary

Introduction

Intracerebral hemorrhage (ICH), which is characterized by high mortality and disability, is the most severe form of stroke with no effective treatment modality, considerable progress has been made in animal and preclinical research [1, 2]. The formation and expansion of ICH results in mechanical damage of the brain tissue, followed by edema, inflammation, and necrosis, which lead to the destruction of neurons and glial structures, an aberrant release of the neurotransmitters and mitochondrial dysfunction, and to apoptosis. In the central nervous system (CNS), astrocytes constitute one of several types of glial cells, which provide structural support and nutritional supply for neurons and help maintain homeostasis of the extracellular www.aging-us.com environment [3, 4]. In response to the CNS is threatened and damaged, such as nerve injury, infection, ischemia, hemorrhagic stroke, or neurodegeneration, astrocytes are activated, which causes them to proliferate, migrate, and to form glial scars [5]. A better understanding of the potential mechanisms underlying astrocyte activation may help to improve the prognosis of patients

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