Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium.
OBJECTIVE
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.


RESULTS
MSCs were cultured and then incubated in medium for 60 min without SDF-1 (control group) or with SDF-1 0.05 microg/mL (SDF-1 group) or CXCR4-selective antagonist, AMD 3100 (AMD) (5 microg/mL, AMD group) or SDF-1 and AMD (0.05 microg/mL, 5 microg/mL, respectively, SDF-1+AMD group). MSCs were treated for 60 min, washed in normal medium, and then exposed to H2O2 (100 micromol/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 microL Dulbecco's modified Eagle's medium without cells or with 5 x 10(5) 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.


CONCLUSIONS
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.
Pasha
Zeeshan
Z
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
Wang
Yigang
Y
Sheikh
Riazuddin
R
Zhang
Dongsheng
D
Zhao
Tiemin
T
Ashraf
Muhammad
M
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000502:physiology; D019610:Cytoprotection; D005260:Female; D019157:Ischemic Preconditioning, Myocardial; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D009203:Myocardial Infarction / Q000628:therapy*; D018919:Neovascularization, Physiologic; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D019718:Receptors, CXCR4 / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases