Abstract 154: Allogeneic Cardiosphere-derived Cells From an Aged Donor Elicit Long-term Improvements in Left Ventricular Function and Myocyte Proliferation in a Mini-swine Model of Chronic Myocardial Ischemia

Autor: Brian R Weil, Gen Suzuki, Merced M Leiker, Andrew Goelz, John M Canty
Rok vydání: 2015
Předmět:
Zdroj: Circulation Research. 117
ISSN: 1524-4571
0009-7330
DOI: 10.1161/res.117.suppl_1.154
Popis: Objective: Virtually all large animal studies of cell-based therapy have employed young donor-recipient pairs. Since aging may impact the reparative ability of allogeneic cardiosphere-derived cells (CDCs), we tested whether CDCs from an aged donor promote functional repair of ischemic myocardium using a mini-swine model that enabled serial assessment of left ventricular (LV) function over an extended follow-up period. Methods: Immunosuppressed mini-swine (cyclosporine 100 mg/day) with a chronic (4-months) LAD stenosis were untreated (n=8) or received 20 million allogeneic aged CDCs (n=10). Cells were cultivated from a 9-year old mini-pig and infused into the 3 major coronary arteries under continuous flow (1 million cells/min). LV function was assessed by echocardiography at baseline and over a 3-month follow-up period, at which time histological assessment of myocyte morphometry, proliferation (Ki67), and cell retention (Y-FISH) was performed. Results: Wall thickening (WT) of the ischemic LAD region was impaired at baseline (LAD: 42.7 ± 2.1% vs. Remote: 81.4 ± 4.8%, p2 , p=0.02) and reduction in myocyte diameter (13.9 ± 0.2 vs. 14.5 ± 0.3 μm, p=0.05). Increases in Ki67 + myocytes (468 ± 92 vs. 199 ± 32 nuclei/10 6 myocyte nuclei, p=0.02) and rare Y + cells in sex-mismatched recipients (0.5 ± 0.2 cells/cm 2 ) supported endogenous myocyte proliferation as the primary source of new myocytes. Conclusion: CDCs from an aged donor retain their reparative capacity to promote functional improvement and increase myocyte number following global intracoronary infusion. The progressive improvement in LV function 3-months after treatment with ongoing myocyte proliferation supports a long-lasting benefit after a single infusion.
Databáze: OpenAIRE
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