Oncotarget

Research Papers:

Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

Qun Zhang, Song Liu, Tong Li, Lin Yuan, Hansen Liu, Xueer Wang, Fuwu Wang, Shuanglian Wang, Aijun Hao, Dexiang Liu and Zhen Wang _

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Oncotarget. 2016; 7:58089-58104. https://doi.org/10.18632/oncotarget.11166

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Abstract

Qun Zhang1, Song Liu1, Tong Li1, Lin Yuan1, Hansen Liu2, Xueer Wang1, Fuwu Wang3, Shuanglian Wang1, Aijun Hao3, Dexiang Liu2, Zhen Wang1,3

1Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China

2Department of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China

3Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China

Correspondence to:

Dexiang Liu, email: [email protected]

Zhen Wang, email: [email protected]

Keywords: hydrogen sulfide, bone marrow mesenchymal stem cells, transplants, brain-derived neurotrophic factor, vascular endothelial growth factor

Received: February 08, 2016     Accepted: July 27, 2016     Published: August 09, 2016

ABSTRACT

Bone marrow mesenchymal stem cells (BMSCs) transplantation has shown great promises for treating various brain diseases. However, poor viability of transplanted BMSCs in injured brain has limited the therapeutic efficiency. Hypoxia-ischemic injury is one of major mechanisms underlying the survival of transplanted BMSCs. We investigated the mechanism of preconditioning of BMSCs with hydrogen sulfide (H2S), which has been proposed as a novel therapeutic strategy for hypoxia-ischemic injury. In this study, we demonstrated that preconditioning of NaHS, a H2S donor, effectively suppressed hypoxia-ischemic-induced apoptosis whereby the rise in Bax/Bcl-2 ratio. Further analyses revealed Akt and ERK1/2 pathways were involved in the protective effects of NaHS. In addition, NaHS preconditioning increased secretion of BDNF and VEGF in BMSCs. Consistent with in vitro data, transplantation of NaHS preconditioned BMSCs in vivo further enhanced the therapeutic effects of BMSCs on neuronal injury and neurological recovery, associated with increased vessel density and upregulation of BDNF and VEGF in the ischemic tissue. These findings suggest that H2S could enhance the therapeutic effects of BMSCs. The underlying mechanisms might be due to enhanced capacity of BMSCs and upregulation of protective cytokines in the hypoxia tissue.


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