Transplantation of Mesenchymal Stem Cells Preconditioned with Hydrogen Sulfide Enhances Repair of Myocardial Infarction in Rats

Abstract

Stem cell transplantation has become a promising therapeutic approach for the treatment of myocardial infarction (MI). However, the poor survival of the donor cells after transplantation has restricted its therapeutic efficacy. Hydrogen sulfide (H 2 S), one gaseous signaling molecule, has been applied to inhibit cell apoptosis and promote cell survival. In the present study, we therefore examined the effects of H 2 S on the survival of mesenchymal stem cells (MSCs). MSCs were isolated from the femur of male Sprague-Dawley rats (about 4 weeks old, 100 g). Preconditioning MSCs with 200 μmol/L NaHS (as the donor of H 2 S) for 30 min decreased the hypoxia-induced cell apoptosis in vitro. The mechanisms contributing to the beneficial effects of H 2 S on MSCs were associated with increased levels of phosphorylated Akt (pAkt), phosphorylated Erk1/2 (pErk1/2) and phosphorylated glycogen synthase kinase-3β (pGSK-3β) in MSCs. Subsequently, MSCs (1 × 10 6 ), MSCs preconditioned with H 2 S (1 × 10 6 ), or phosphate buffered saline (PBS) were injected into rat hearts immediately after MI (the ligation of the left anterior descending of coronary artery). Real-time PCR for the Sry gene, located on the Y chromosome, indicated that preconditioning with H 2 S improved the survival rate of the transplanted MSCs in infarcted myocardium 4 days after MI, compared with the untreated MSCs. Furthermore, transplantation of the H 2 S-pretreated MSCs reduced the infarct size and increased left ventricular (LV) function, as judged by transthoracic echocardiography. In conclusion, H 2 S preconditioning effectively promotes MSCs survival under ischemic injury and helps cardiac repair after MI, which has great clinical significance.

Hydrogen Sulfide, the Next Potent Preventive and Therapeutic Agent in Aging and Age-Associated Diseases

“…H 2 S has been applied to inhibit cell apoptosis and promote cell survival in such cases. It has been demonstrated that H 2 S preconditioning effectively promotes stem cell survival under conditions of ischemic injury and helps cardiac repair after MI (92).…”

Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells

“…These findings suggest that modulation of H 2 S metabolism may serve as a therapeutic approach to promote the viability of transplanted MSCs and facilitate MSC-based regeneration. Consistent with this, it was reported that H 2 S improves transplanted MSC survival in infarcted myocardium and aids in cardiac repair (Xie et al 2012). To further understand the role of H 2 S on transplanted MSCs and translate these findings from the bench top to the clinic, more studies of preclinical animal models are needed.…”

“…H 2 S has recently been proposed as an endogenous mediator or inhibitor of cell apoptosis in various systems. H 2 S treatment could increase MSC proliferation and survival and attenuate hypoxia-, oxidant-, or serum deprivation-induced apoptosis (Fox et al 2012;Xie et al 2012;Zhao et al 2013;Li et al 2014;Aykan et al 2015;Guo et al 2015). Mechanically, H 2 S activates PI3K/Akt, Erk1/2, and GSK-3β (glycogen synthase kinase-3β) pathways to decrease hypoxia-induced MSC apoptosis.…”

“…For instance, H 2 S activates PKC/Erk-mediated Wnt/β-catenin signaling to promote osteogenic differentiation of MSCs (Liu, Yang, et al 2014;Grassi et al 2015). Furthermore, H 2 S activates the PI3K/Akt, Erk1/2, and GSK-3β pathways, thereby decreasing hypoxia-induced MSC apoptosis (Fox et al 2012;Xie et al 2012;Li et al 2014;Guo et al 2015).…”

Hypothetical Formulation to Propel Pico-molecular Medicinal Dust: Application to Total Elevation of Therapeutic Efficiency Compare to Nano Entity

“…Antimicrobial agent (s) delivery of Nanoparticle-medium into pathogen-containing intracellular vacuoles in macrophages could be useful and help to removing cellular reservoirs [19]. A simple one-step procedure to obtain CS-TPP and concomitant complexion with sodium alginate was implicated, to prepare trans mucosal formulations for the absorption of insulin [20]. Developed PLGA nanoparticles intended for the transdermal application of encapsulated glucosamine, which is a highly hydrophilic and poor permeable drug.…”