Mesenchymal stem cells implantation increases the myofibroblasts congregating in infarct region in a rat model of myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI).</p><p><b>METHODS</b>MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region). Echocardiography, hemodynamic examinations and Masson trichrome staining were performed. Implanted MSC differentiation and myofibroblasts congregating in infarct region were investigated by immunofluorescence staining. TGF-β(1)-Smad2 signaling pathway was examined by real-time RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) Four weeks late, heart-weight/body-weight ratio [(3.04 ± 0.16) mg/g vs. (3.34 ± 0.14) mg/g, P < 0.01] and myocardial infarction size [(38.72 ± 2.38)% vs. (46.36 ± 2.81)%, P < 0.01] were significantly reduced in MI + MSC group than in MI + PBS group, while scar thickness of infarct region was thicker [(0.93 ± 0.17) mm vs. (0.65 ± 0.16) mm, P = 0.01], and LVEF was higher [LVEF: (32.5 ± 5.9)% vs. (26.5 ± 4.5)%, P = 0.03] in MI + MSC group than in MI + PBS group. (2) Myofibroblasts congregating in the infarct region was significantly enhanced in MI + MSC group compared with MI + PBS group [(196 ± 20) cells/mm(2) vs. (89 ± 25) cells/mm(2), P < 0.01], and part of implanted MSC expressed α-SMA(+). (3) TGF-β(1) expression and the phosphorylating of Smad2 in the infarct region were significantly upregulated in MI + MSC group compared with MI + PBS group (all P < 0.05).</p><p><b>CONCLUSIONS</b>MSC could improve myocardial function and promote myofibroblasts congregating in the infarct region via activating the TGF-β(1)-Smad2 signaling pathway in this model.</p>

Dural modulation effects of mesenchymal stem cells implantation on myocardial collagen remodeling in a rat model of myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the modulation effects of mesenchymal stem cells (MSCs) implantation on the collagen remodeling in myocardial infarction.</p><p><b>METHODS</b>Acute myocardial infarction (AMI) was induced in SD rats by left anterior descending coronary artery ligation, and the animals were assigned randomly into the Sham group, MI + PBS group and MI + MSCs group. Echocardiography and hemodynamic examinations were performed to evaluate the cardiac function. HE staining and Masson trichrome staining were used to evaluate the myocardial infarction size. Infarcted area and infarcted expansion index were calculated. The expression of collagens in infarcted hearts was evaluated by immunohistochemistry, RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) Infarct area was significantly reduced post MSCs transplantation [MI + MSCs vs. MI + PBS: (38.27 ± 2.70)% vs. (46.20 ± 3.17)%, P < 0.001]. (2) Cardiac function was significantly improved post MSCs transplantation [MI + MSCs vs. MI + PBS: FS(%): 29.98 ± 4.50 vs. 23.43 ± 3.34, P = 0.005; LVSP (mm Hg, 1 mm Hg = 0.133 kPa): 113.63 ± 10.81 vs. 99.25 ± 16.76, P < 0.05; LVEDP (mm Hg): 12.10 ± 4.28 vs. 20.08 ± 4.26, P < 0.05; +dp/dtmax (mm Hg/s): 4616.63 ± 363.34 vs. 3912.75 ± 248.79, P < 0.05; -dp/dtmax (mm Hg/s): 4254.63 ± 324.34 vs. 3530.88 ± 309.71, P < 0.05]. (3) Collagen synthesis was enhanced in infarcted area and decreased in non-infarcted area post MSCs transplantation (P < 0.05).</p><p><b>CONCLUSIONS</b>MSCs transplantation could enhance the collagen synthesis in infarcted area while decrease the deposition of collagen in non-infarcted area in this MI model. This may be one of the mechanisms by which ventricular remodeling is attenuated post MSCs transplantation.</p>

Inhibition of Nuclear Factor-?B Activity by Mesenchymal Stem Cells in Rats with Myocardial Infarction / 中华高血压杂志

Objective To investigate the effect of mesenchymal stem cells (MSC) on the activity of nuclear factor (NF)-?B in rats with myocardial infarction.Methods MSC were isolated from SD rats (120—150 g in weight).SD rats (180—200 g in weight) were subjected to MI by left coronary artery occlusion,and were allo- cated into three groups randomly:1)sham group (without ligation of the artery,n=8);2)injection of PBS solu- tion (n=8);3)injection of MSC (n=8).MSC or PBS solution was injected into myocardium from epicardium instantly after MI models were established.Four weeks after transplantation,cardiac function was evaluated u- sing physiological recorder.Western blot were performed to investigate the nuclear factor-? activity.The ex- pressions of tumor necrosis factor (TNF)-? and interleukin (IL)-6 were evaluated by RT-PCR and Western blot. Results 1)Mortality was 20%(2/10) in sham group,33.3%(4/12) in PBS group and 20%(2/10) in MSC group with no statistic differences between them(P=0.646).2) Hemodynamic measurements showed that MSC trans- plantation caused significant improvement in cardiac function,comparing with MI+PBS group.3) MSC inhibi- ted the activities of NF-?B in myocardium and down-regulated the expression of TNF-? and IL-6 in mRNA and protein level.Conclusion Transplantation of MSC improved cardiac function in MI rats,which may partly at- tribute to their immuno-inflammatory regulation mechanism.