Delayed Enrichment for c‐kit and Inducing Cardiac Differentiation Attenuated Protective Effects of BMSCs' Transplantation in Pig Model of Acute Myocardial Ischemia. Issue 4 (7th July 2015)

• Record Type: Journal Article
• Authors: Zhang, Guang‐Wei; Gu, Tian‐Xiang; Guan, Xiao‐Yu; Sun, Xue‐Jun; Jiang, Da‐Qing; Tang, Rui; Qi, Xun; Li, Xue‐Yuan
• Is Part Of: Cardiovascular therapeutics. Volume 33:Issue 4(2015:Aug.)
• Page Start: 184
• Page End: 192
• Publication Date: 2015-07-07
• Subjects: Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular system -- Diseases -- Chemotherapy -- Periodicals; Cardiovascular Agents -- Periodicals; Cardiovascular Diseases -- drug therapy -- Periodicals; Agents cardiovasculaires -- Périodiques; Appareil cardiovasculaire -- Maladies -- Chimiothérapie -- Périodiques; 616.1005
• DOI: 10.1111/1755-5922.12131
• Languages: English
• ISSNs: 1755-5914

Abstract

<abstract abstract-type="main" id="cdr12131-abs-0001"> <title>Summary</title> <sec id="cdr12131-sec-0001" sec-type="section"> <title>Objective</title> <p>To investigate the effects of immature cardiomyocytes differentiated from c‐kit<sup>+</sup> bone marrow mesenchymal stem cells (BMSCs) against acute myocardial infarction (AMI).</p> </sec> <sec id="cdr12131-sec-0002" sec-type="section"> <title>Methods</title> <p>Miniswine passage 8 BMSCs were enriched for c‐kit and induced by 5 <italic>μ</italic>M 5‐azacytidine (AZA) for 14 days, and a second enrichment for the dihydropyridine receptor subunit <italic>α</italic>2<italic>δ</italic>1 was performed (enriched BMSCs). Thereafter, enriched BMSCs were analyzed by determining cardiac differentiation, secretion function, and the effects of these secreted factors on cardiac stem cells (CSCs). Miniswine with AMI were divided into control, primary BMSCs' (PB), and enriched BMSCs' (EB) groups. Autologous BMSCs were intramyocardially injected into the ischemic regions in PB and EB groups. The following indices were evaluated at different time points, including paracrine of implanted BMSCs, histological and morphological analysis, myocardial perfusion, and cardiac function.</p> </sec> <sec id="cdr12131-sec-0003" sec-type="section"> <title>Results</title> <p>As shown by <italic>in vitro</italic> study, enrichment + AZA significantly promoted BMSCs to express cardiac‐specific markers and format action potential, but down‐regulated the expression of VEGF and bFGF, consequently attenuated BMSCs‐inducing CSCs proliferation, migration, and differentiation. The <italic>in vivo</italic> experiments revealed similar results like the <italic>in vitro</italic> 6 weeks postoperatively. And in EB group, there were decreased angiogenesis and myocardial perfusion, attenuated resident CSCs‐mediated myocardial regeneration, and consequently impaired cardiac function compared with PB group.</p> </sec> <sec id="cdr12131-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This pretreatment promoted BMSCs to differentiate into myocardiocytes both <italic>in vitro</italic> and <italic>in vivo</italic>, but impaired their paracrine function and effects on resident CSCs, suggesting that inducing cardiac differentiation alone may not improve protective effects of BMSCs transplantation on AMI.</p> </sec> </abstract>