TY - JOUR
T1 - Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium
AU - Pasha, Zeeshan
AU - Wang, Yigang
AU - Sheikh, Riazuddin
AU - Zhang, Dongsheng
AU - Zhao, Tiemin
AU - Ashraf, Muhammad
N1 - Funding Information:
This work was supported by National Institutes of Health grants, HL 23597, HL 080686, HL 70062, R 37-HL 074272 and HL 087246 (M.A.); HL-081859-01 (Y.W.).
PY - 2008/1
Y1 - 2008/1
N2 - Aims: We hypothesized that preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) significantly enhances cell survival, proliferation, and engraftment of bone marrow-derived mesenchymal stem cells (MSCs) via SDF-1/CXCR4 signaling. Methods and results: MSCs were cultured and then incubated in medium for 60 min without SDF-1 (control group) or with SDF-1 0.05 μg/mL (SDF-1 group) or CXCR4-selective antagonist, AMD 3100 (AMD) (5 μg/mL, AMD group) or SDF-1 and AMD (0.05 μg/mL, 5 μg/mL, respectively, SDF-1+AMD group). MSCs were treated for 60 min, washed in normal medium, and then exposed to H 2O2 (100 μmol/L) for 60 min to determine the effects of various treatments on cell injury, viability, and proliferation. For in vivo studies, rats were grouped (n = 6) after left anterior descending coronary artery ligation to receive 20 μL Dulbecco's modified Eagle's medium without cells or with 5 × 105 non-preconditioned MSCs (control group), SDF-1 preconditioned MSCs (SDF-1 group), AMD (AMD group), or MSCs treated with SDF-1 plus AMD (SDF-1+AMD group). Heart function, infarct size, fibrosis, and MSC proliferation and differentiation in infarcted myocardium were determined after 4 weeks. In vitro data showed a marked increase in cell viability and proliferation following SDF-1 PC. In vivo data in preconditioned group showed a robust cell proliferation, reduction in infarct size and fibrosis, and significant improvement in cardiac function. Effects of SDF-1 PC were abrogated by CXCR4 antagonist. Conclusion: We conclude that PC with the chemokine SDF-1 suppresses MSCs apoptosis, enhances their survival, engraftment, and vascular density, and improves myocardial function via SDF/CXCR4 signaling. Chemokine PC is a novel approach for enhancing stem cell survival and regeneration of infarcted myocardium.
AB - Aims: We hypothesized that preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) significantly enhances cell survival, proliferation, and engraftment of bone marrow-derived mesenchymal stem cells (MSCs) via SDF-1/CXCR4 signaling. Methods and results: MSCs were cultured and then incubated in medium for 60 min without SDF-1 (control group) or with SDF-1 0.05 μg/mL (SDF-1 group) or CXCR4-selective antagonist, AMD 3100 (AMD) (5 μg/mL, AMD group) or SDF-1 and AMD (0.05 μg/mL, 5 μg/mL, respectively, SDF-1+AMD group). MSCs were treated for 60 min, washed in normal medium, and then exposed to H 2O2 (100 μmol/L) for 60 min to determine the effects of various treatments on cell injury, viability, and proliferation. For in vivo studies, rats were grouped (n = 6) after left anterior descending coronary artery ligation to receive 20 μL Dulbecco's modified Eagle's medium without cells or with 5 × 105 non-preconditioned MSCs (control group), SDF-1 preconditioned MSCs (SDF-1 group), AMD (AMD group), or MSCs treated with SDF-1 plus AMD (SDF-1+AMD group). Heart function, infarct size, fibrosis, and MSC proliferation and differentiation in infarcted myocardium were determined after 4 weeks. In vitro data showed a marked increase in cell viability and proliferation following SDF-1 PC. In vivo data in preconditioned group showed a robust cell proliferation, reduction in infarct size and fibrosis, and significant improvement in cardiac function. Effects of SDF-1 PC were abrogated by CXCR4 antagonist. Conclusion: We conclude that PC with the chemokine SDF-1 suppresses MSCs apoptosis, enhances their survival, engraftment, and vascular density, and improves myocardial function via SDF/CXCR4 signaling. Chemokine PC is a novel approach for enhancing stem cell survival and regeneration of infarcted myocardium.
KW - Apoptosis
KW - Infarction
KW - Myoangiogenesis
KW - Preconditioning
KW - Stromal-derived factor 1 alpha
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U2 - 10.1093/cvr/cvm025
DO - 10.1093/cvr/cvm025
M3 - Article
C2 - 18006467
AN - SCOPUS:38849108184
SN - 0008-6363
VL - 77
SP - 134
EP - 142
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -