Abstract 25: A Streamlined Technique to Stabilize C-kit Expression in Cardiac Mesenchymal Cells

• Published in: Circulation research Vol. 119; no. suppl_1
• Main Authors: Dassanayaka, Sujith, Long, Bethany W, Zafir, Ayesha, Ghafghazi, Shahab, Hunt, Gregory N, Noble, Camille T, DeMartino, Angelica M, Brittian, Kenneth R, Jones, Steven P, Wysoczynski, Marcin
• Format: Journal Article
• Language: English
• Published: 22-07-2016
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.119.suppl_1.25

Abstract only
Adoptive transfer of various reparative cells attenuates cardiac dysfunction in preclinical models of heart failure. Although c-kit sorted cells do not transdifferentiate to an extent sufficient to explain improvements in ventricular function, their adoptive transfer reliably attenuates cardiac dysfunction. Curiously, few studies report maintenance of c-kit expression with passage, and our experience indicates rapid dissipation of c-kit. Here, we asked whether we could stabilize c-kit expression during passage of c-kit sorted cells. To this end, we standardized an approach to isolate c-kit
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cardiac mesenchymal cells (CMCs) and to preserve c-kit expression over several passages (panel A). This protocol was predicated on the differential adhesion capacity of c-kit sorted CMCs, allowing their stratification into two groups: rapidly adhering (RA) and slowly adhering (SA). After characterization of these cells (panel B), we tested their reparative capacity using echo-guided, percutaneous intracavitary delivery in mice at two days following myocardial infarction (MI). SA, but not RA, CMCs significantly reduced scar area and improved ejection fraction (EF) compared to [cell-free] vehicle (panels C, D, and E). Examination of the post-MI hearts indicated augmented ischemic zone capillary formation in the SA group (panel F), consistent with potential neovascularization. In conclusion, we established a method to stabilize c-kit expression in a reparative subset of CMCs (i.e. SA CMCs). Our results, however, did not reconcile whether such maintenance of c-kit expression is required for the reparative function of the SA CMCs, which is the subject of future investigation.