Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction.
BACKGROUND
There are several reports that engrafted mesenchymal stem cells (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains controversial. We hypothesize that transplantation of MSCs enhances vascular regeneration through a paracrine action.


METHODS
A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 x 10(7); 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 microL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation.


RESULTS
The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1alpha) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40% in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6% +/- 19.9%; medium: 18.7% +/- 6.4%; p = 0.004).


CONCLUSIONS
Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.
Department of Physiology and Biophysics, College of Medicine, University of South Florida, St. Petersburg, Florida, USA. ytang@hsc.usf.edu
Yao Liang
YL
Tang
Qiang
Q
Zhao
Xinyu
X
Qin
Leping
L
Shen
Leilei
L
Cheng
Junbo
J
Ge
M Ian
MI
Phillips
D043924:Angiogenesis Modulating Agents; D000818:Animals; D002196:Capillaries / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D014182:Transplantation, Autologous
D043924:Angiogenesis Modulating Agents