Abstract 16365: Juvenile Skeletal Myoblast Has Greater Therapeutic Potentials in Regenerative Therapy Than Adult Sheet for Treating Chronic Myocardial Infarction in Juvenile Pig
Background: Autologous cell transplantation therapy has been shown to be effective in treating chronic myocardial infarction (MI). Meanwhile, the fundamental behaviors of juvenile-derived cells, including proliferation and sirtuin (Sirt) 1 expression, are different from those of adult-derived cells. We hypothesized that the therapeutic effects of autologous skeletal myoblast (SMB) sheet transplantation for treating chronic MI are different between juvenile and adult individuals.
Methods and Results: Primary SMB cultures were established in male juvenile (2-month-old) and adult (10-month-old) mini-pigs. The ratio of Ki67-positive cells was significantly greater in juvenile cells than in adult cells (8 ± 3% vs. 3 ± 2%, P = 0.005). Sirt1, HGF, and SDF-1 mRNAs were significantly upregulated in juvenile cells than in adult, as assessed by real-time PCR (4.7 ± 3.3 vs. 1.4 ± 0.6, 4.0 ± 2.3 vs. 1.0 ± 0.4, and 1.6 ± 0.1 vs. 0.5 ± 0.4, respectively). Moreover, the culture medium contained a greater level of vascular endothelial growth factor in juvenile cells than in adult cells, as assessed by ELISA (1.2 ± 0.9 vs. 0.2 ± 0.2 μg/mL). Next, we induced chronic MI by the catheterized left anterior descending artery occlusion and revascularization method. Two months later, cultured SMBs were prepared as cell sheets and transplanted into corresponding MI-pigs (n = 4 each). Echocardiographically, the ejection fraction was significantly improved in both juvenile (27± 6% vs. 43 ± 4%) and adult (30± 1% vs. 45± 6%) pigs. In addition, the dissynchrony index was significantly improved in model juvenile pigs compared with sham-operated juvenile pigs (54 ± 4 vs. 149 ± 3 ms, respectively, P = 0.001), as assessed by 3-dimensional tracking echocardiography. Importantly, the number of CD31-positive capillaries in the infarct-border region was significantly and markedly greater in juvenile pigs than in adult pigs (8.7± 2.7% vs 3.3± 2.1%, p = 0.005).
Conclusions: Skeletal myoblasts derived from juvenile pigs showed a greater proliferative and angiogenic potential than those derived from adult pigs, leading to enhanced positive therapeutic effects on chronic MI in juvenile pig. Autologous cell-sheet transplantation may be warranted as a novel treatment for pediatric cardiomyopathy.
- © 2013 by American Heart Association, Inc.