Myocardial Reparative Properties of Cardiac Mesenchymal Cells Isolated on the Basis of Adherence

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:69

Article

Wysoczynski, Marcin^1,2  Guo, Yiru¹  Moore, Joseph B.¹  Muthusamy, Senthilkumar¹  Li, Qianhong¹  Nasr, Marjan¹  Li, Hong¹  Nong, Yibing¹  Wu, Wenjian¹  Tomlin, Alex A.¹  Zhu, Xiaoping¹  Hunt, Gregory¹  Gumpert, Anna M.¹  Book, Michael J.¹  Khan, Abdur¹  Tang, Xian-Liang¹  Bolli, Roberto^1,2 

[1] Univ Louisville, Sch Med, Inst Mol Cardiol, Louisville, KY 40292 USA

[2] Univ Louisville, Sch Med, Diabet & Obes Ctr, Louisville, KY 40292 USA

关键词: fibrosis;    inflammation;    ischemic cardiomyopathy;    myocardial infarction;    repair;   

DOI  :  10.1016/j.jacc.2017.01.048

来源: Elsevier

【 摘 要 】

BACKGROUND The authors previously reported that the c-kit-positive (c-kitPOS) cells isolated from slowly adhering (SA) but not from rapidly adhering (RA) fractions of cardiac mesenchymal cells (CMCs) are effective in preserving left ventricular (LV) function after myocardial infarction (MI). OBJECTIVES This study evaluated whether adherence to plastic alone, without c-kit sorting, was sufficient to isolate reparative CMCs. METHODS RA and SA CMCs were isolated from mouse hearts, expanded in vitro, characterized, and evaluated for therapeutic efficacy in mice subjected to MI. RESULTS Morphological and phenotypic analysis revealed that murine RA and SA CMCs are indistinguishable; nevertheless, transcriptome analysis showed that they possess fundamentally different gene expression profiles related to factors that regulate post-MI LV remodeling and repair. A similar population of SA CMCs was isolated from porcine endomyocardial biopsy samples. In mice given CMCs 2 days after MI, LV ejection fraction 28 days later was significantly increased in the SA CMC group (31.2 +/- 1.0% vs. 24.7 +/- 2.2% in vehicle-treated mice; p < 0.05) but not in the RA CMC group (24.1 +/- 1.2%). Histological analysis showed reduced collagen deposition in the noninfarcted region in mice given SA CMCs (7.6 +/- 1.5% vs. 14.5 +/- 2.8% in vehicle-treated mice; p < 0.05) but not RA CMCs (11.7 +/- 1.7%), which was associated with reduced infiltration of inflammatory cells (14.1 +/- 1.6% vs. 21.3 +/- 1.5% of total cells in vehicle and 19.3 +/- 1.8% in RA CMCs; p < 0.05). Engraftment of SA CMCs was negligible, which implies a paracrine mechanism of action. CONCLUSIONS We identified a novel population of c-kit-negative reparative cardiac cells (SA CMCs) that can be isolated with a simple method based on adherence to plastic. SA CMCs exhibited robust reparative properties and offered numerous advantages, appearing to be more suitable than c-kitPOS cardiac progenitor cells for widespread clinical therapeutic application. (C) 2017 by the American College of Cardiology Foundation.

【 授权许可】

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