title: Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential.
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.
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Qun
authors: Q
authors: Zhang
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Song
authors: S
authors: Liu
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Tong
authors: T
authors: Li
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Lin
authors: L
authors: Yuan
authors: Department of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Hansen
authors: H
authors: Liu
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Xueer
authors: X
authors: Wang
authors: Key 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.
authors: Fuwu
authors: F
authors: Wang
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Shuanglian
authors: S
authors: Wang
authors: Key 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.
authors: Aijun
authors: A
authors: Hao
authors: Department of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors: Dexiang
authors: D
authors: Liu
authors: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.|Key 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.
authors: Zhen
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001927:Brain Diseases / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C000617196:Bcl2 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C467498:vascular endothelial growth factor A, rat; D051057:Proto-Oncogene Proteins c-akt; D006862:Hydrogen Sulfide
keywords: bone marrow mesenchymal stem cells; brain-derived neurotrophic factor; hydrogen sulfide; transplants; vascular endothelial growth factor