Mechanisms of the protective effects of BMSCs promoted by TMDR with heparinized bFGF-incorporated stent in pig model of acute myocardial ischemia.
This study investigates the mechanism by which transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor incorporated degradable stent implantation (TMDRSI) enhanced effects of bone marrow mesenchymal stem cells (BMSCs) transplantation against acute ischemic myocardial injury. After the mid-third of left anterior descending artery was ligated, miniswine were divided into none-treatment group (control, n = 6), BMSCs implantation group (C, n = 6), TMDRSI group (TS, n = 6) and TMDRSI and BMSCs implantation group (TSC, n = 6). Two channels of 3.5 mm diameter were established by a self-made drill in the ischemic region, into which a stent was implanted for the TS and TSC groups. Autologous BMSCs were transplanted into the ischemic region in C group or around the channels in TSC group. Expression of von Willebrand factor, vascular endothelial growth factor, interleukin-1β, transforming growth factor-β(3) , cell proliferation and apoptosis, histological and morphological analyses, myocardial remodelling and cardiac function were evaluated at different time-points. Six weeks after the operation, the above indices were significantly improved in TSC group compared with others (P < 0.05), though C and TS groups also showed better results than the control group (P < 0.05). The new method was shown to have activated paracrine pathway of transplanted BMSCs, increased survival and differentiation of such cells, and enhanced effects of BMSCs transplantation on myocardial remodelling, which may provide a new strategy for cell therapies against acute ischemic myocardial injury.
Zhang
Guang-Wei
GW
Department of Surgery, Tianjin Medical University Cardiovascular Clinical College & TEDA International Cardiovascular Hospital, Tianjin, China.
Liu
Xiao-Cheng
XC
Li-Ling
Jesse
J
Luan
Yun
Y
Ying
Yuan-Ning
YN
Wu
Xue-Sheng
XS
Zhao
Chun-Hua
CH
Liu
Tian-Jun
TJ
Lü
Feng
F
D054058:Acute Coronary Syndrome / Q000473:pathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009204:Myocardial Revascularization; D015607:Stents; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects
D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin
Stem Cells Dev. 2008 Aug;17(4):725-36
18788932
Stem Cells. 2004;22(3):377-84
15153614
Circulation. 2006 Mar 14;113(10):1287-94
16520413
J Mol Cell Cardiol. 2009 Aug;47(2):315-25
19328809
J Clin Invest. 2005 Feb;115(2):326-38
15690083
Nat Med. 2004 May;10(5):494-501
15107841
Cardiovasc Res. 2009 Dec 1;84(3):461-9
19578069
Nat Med. 2006 Apr;12(4):459-65
16582917
Lancet. 2004 Jul 10-16;364(9429):141-8
15246726
Circulation. 2009 May 19;119(19):2587-96
19414636
J Surg Res. 2010 Dec;164(2):204-13
19691971
Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17783-8
17965233
J Am Coll Cardiol. 2008 Dec 2;52(23):1858-1865
19038683
J Clin Invest. 2006 Jul;116(7):1865-77
16823487
N Engl J Med. 2006 Sep 21;355(12):1199-209
16990383
Circulation. 2005 Aug 23;112(8):1128-35
16103243
N Engl J Med. 2006 Sep 21;355(12):1210-21
16990384
N Engl J Med. 2006 Sep 21;355(12):1222-32
16990385
Circulation. 2004 Mar 30;109(12):1543-9
15023891
Circ Res. 2006 Jun 9;98(11):1414-21
16690882