Abstract 12166: The Synergy Between Mesenchymal Stem Cells and Controlled Release of Thymosin β4 for Cardiac Repair
Objective: We investigated the feasibility and efficacy of a synergy between mesenchymal stem cells (MSCs) and controlled release of thymosin β4 (Tβ4) for cardiac repair in a rat heart model of myocardial infarction (MI).
Methods: The protection of Tβ4 on MSCs against hypoxia (5% CO2+ 94% N2+1% O2,48 hours) injury was determined and characterized. Gelatin microsphere was used for the controlled release of Tβ4 (M-Tβ4) in vitro and in vivo. A fibrin patch was used to simultaneously deliver MSCs and M-Tβ4 in a rat heart model of MI: group-1=DMEM injection (n=5), group-2=Patch transplantation (n=5), group-3=Patch+MSCs transplantation (n=5), group-4=Patch+MSCs+M-Tβ4 transplantation (n=6). Echocardiography was performed to assess the heart function at 1 and 4 weeks after surgery. Left ventricule (LV) anterior wall blood flow and immunohistochemistry studies were studied at 4 weeks after surgery.
Results: No significant toxicity of Tβ4 towards MSCs was found when Tβ4 was increased up to 2 µg/ml in vitro. Tβ4 significantly enhanced MSCs viability under hypoxia up to 48 hours. Tβ4 increased the protein expression of pAKT (Ser-473) and Bcl-XL, decreased caspase-3 activity and apoptosis of MSCs under hypoxia. Gelatin microsphere study demonstrated a sustained and controlled release of Tβ4 could be achieved up to 14 days in vitro. Animal studies revealed reduced infarct size and increased LV wall thickness of group-4 as compared with other groups at 4 weeks after treatment (p<0.05). LV anterior wall vessel density (per mm2) by immunostaining for CD31 expression was the highest in group-4 (1029±213, p<0.05) as compared to group-1 (567±184), group-2 (644±275), and group-3 (770±125) at 4 weeks after treatment. Improved ejection fraction (EF) and fraction shortening (FS) were most recovered in group-4 group. The significant improved LV pump function was found between group-4 (EF=51.5±3.8%, FS=26.5±2.1%, p<0.05 for both) and group-1 (EF=38.7±9.3%, FS=19.3±5.2%). The addition of Tβ4 significantly attracted more c-Kit progenitor cells into patch and per-infarct myocardium as compared with MSCs only.
Conclusion: The synergy between MSCs and controlled release of Tβ4 provides a better therapeutic strategy than MSCs only for treatment of MI.
- © 2012 by American Heart Association, Inc.