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.
Highlights
A growing number of experimental studies highlights the potential of stem cell transplantation as a novel therapeutic approach for ischemic stroke [1]
We investigated the mechanism of preconditioning of Bone marrow mesenchymal stem cells (BMSCs) with hydrogen sulfide (H2S), which has been proposed as a novel therapeutic strategy for hypoxia-ischemic injury
MTT results showed that sodium hydrosulfide (NaHS) preconditioned BMSCs (PCBMSCs) had a significant reduction in death, compared with the non-preconditioned BMSCs after 48 h (p < 0.01) and 72 h (p < 0.01) hypoxia-ischemic injury
Summary
A growing number of experimental studies highlights the potential of stem cell transplantation as a novel therapeutic approach for ischemic stroke [1]. Transplantation of BMSCs in the acute stage of ischemic stroke often modulates the inflammatory milieu, reduces lesion size and inhibits apoptosis in the penumbra area by providing neuroprotective paracrine factors [3, 5, 6]. Only a small fraction of grafted cells survived in the ischemic brain 28 d after grafting because of the interplay of poor blood supply, ischemia reperfusion, inflammation, and apoptosis. Donor variability is another challenge for BMSC therapy trials
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
