Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair
نویسندگان
چکیده
BACKGROUND The therapeutic efficiency of bone marrow mononuclear cells (BMMNCs) autologous transplantation for myocardial infarction (MI) remains low. Here we developed a novel strategy to improve cardiac repair by preconditioning BMMNCs via angiotensin II type 2 receptor (AT2R) stimulation. METHODS AND RESULTS Acute MI in rats led to a significant increase of AT2R expression in BMMNCs. Preconditioning of BMMNCs via AT2R stimulation directly with an AT2R agonist CGP42112A or indirectly with angiotensin II plus AT1R antagonist valsartan led to ERK activation and increased eNOS expression as well as subsequent nitric oxide generation, ultimately improved cardiomyocyte protection in vitro as measured by co-culture approach. Intramyocardial transplantation of BMMNCs preconditioned via AT2R stimulation improved survival of transplanted cells in ischemic region of heart tissue and reduced cardiomyocyte apoptosis and inflammation at 3 days after MI. At 4 weeks after transplantation, compared to DMEM and non-preconditioned BMMNCs group, AT2R stimulated BMMNCs group showed enhanced vessel density in peri-infarct region and attenuated infarct size, leading to global heart function improvement. CONCLUSIONS Preconditioning of BMMNCs via AT2R stimulation exerts protective effect against MI. Stimulation of AT2R in BMMNCs may provide a new strategy to improving therapeutic efficiency of stem cells for post MI cardiac repair.
منابع مشابه
Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo
Objective(s):To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods:Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To t...
متن کاملCell transplantation for cardiac repair.
Despite remarkable progress in contemporary cardiovascular therapy, treatment of heart failure still remains a therapeutic challenge. Pharmacological treatment using -blockers, angiotensin converting enzyme inhibitors, and angiotensin-II receptor blockers, as well as surgical revascularization together with left ventricular reshaping procedures, has improved the quality of life for heart failur...
متن کاملAre Stem Cells the next Therapeutic Tool for Heart Repair?
Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and Europe. In recent years, the understanding that regenerative processes exist at the level of the myocardium, has placed stem cell research at center stage in cardiology. A stem cell is a cell that has the ability to divide (self replicate) for indefinite periods often throughout the life of the ...
متن کاملIn vitro Effect of Pomalidomide on Bone Marrow Mononuclear Cells from Multiple Myeloma Patients
Background: Many features of anticancer drugs, including cytotoxicity and/or cytokine induction, are studied using cell lines orhuman blood leukocytes. However, in a disease such as multiple myeloma, most cancerous cells are resided within bone marrowmononuclear cells. In the present study, we investigated the effect of pomalidomide on apoptosis and IL-2 production of bonemarrow mononuclear cel...
متن کاملExogenous Nitric Oxide Induced Early Mineralization in Rat Bone Marrow Mesenchymal Stem Cells via Activation of Alkaline Phosphatase
Background: Since the low concentration and short-time treatment with sodium nitroprusside (SNP), a nitric oxide (NO)–donor, cause no harm to rat bone marrow mesenchymal stem cells (MSCs), we studied the impact of SNP on MSCs differentiation. Methods: MSCs were treated with 100 and 1000 µM of SNP for 1 hour in every 48 hours and after 5, 10, 15, and 21 days in osteogenic media. The viability an...
متن کامل