Abstract 18302: Therapeutic Optimization of Mesenchymal Stem Cells by Combinational Application With Primed Stem Cells in Myocardial Infarction Model
Introduction: We have already confirmed that mesenchymal stem cells (MSCs) were highly cardiogenically modified by treatment with compound A (CompA) for 24 hours, and one of critical regulators was yes-associated protein in MSC.
Objective: Here, we developed a novel protocol to maximize the therapeutic effect of primed MSCs.
Methods and Results: CompA -treated MSCs (A/MSCs) dramatically upregulated cardiac markers such as GATA4, cardiac troponin I (cTnI), and Nkx2.5, however, angiogenic activity was slightly reduced. To overcome this phenotype, we mixed naïve MSCs and A/MSCs and named MSC Mix (MSCs+A/MSCs). The angiogenic activity was completely recovered in MSC Mix as detected by tube formation assay and Matrigel plug assay. Importantly, cardiac genes were upregulated significantly in MSC Mix. In animal study, myocardial infarction (MI) was induced in nude mice, and A/MSCs or MSC Mix were injected after 7 days. Cardiac differentiation of injected MSCs was equally observed both in the A/MSCs group and the MSC Mix group. Angiogenesis in the peri-infarct zone was much more increased the MSC Mix group than in the A/MSCs group (p<0.05). Left ventricular wall thickness was more preserved in the MSC Mix group than in the A/MSCs group. Ejection fraction (%) was 35.6±2.8 in the PBS group, 43.5±4.7 in the A/MSC group (p<0.05 vs. PBS group), and 52.9±5.8 in the MSC Mix group (p<0.05 vs. A/MSC group). So far, cardiac differentiation of MSCs is regarded as a skeptical strategy due to its complicated conditions and a low efficacy.
Conclusions: Our study suggested that CompA is a safe inducer for cardiac differentiation of MSCs, and we developed the combinational approach with naïve MSCs and cardiac committed MSC as an optimized technique for cardiac repair.
Author Disclosures: D. Cho: None. W. Kang: None. H. Kang: None. Y. Kim: None. Y. Ahn: None.
- © 2016 by American Heart Association, Inc.