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Objective:
Engraftment of mesenchymal stem cells (MSCs) has emerged as a powerful candidate in mediating myocardial repair. In this study, we genetically modified MSCs with adenovector encoding thioredoxin-1 (Ad.Trx1), apart from its antioxidative role Trx-1 is described as a growth regulator, transcription factor regulator, and a cofactor. We explored whether these transplanted engineered MSCs are capable of improving cardiac function and angiogenesis in a rat MI model
Design:
Sprague Dawley rats were randomized into control sham (CS), Control-MI (CMI), MSC-LacZ-MI (MLZMI) & MSC-Trx-1-MI (MTRXMI) (n=20/group). Myocardial infarction (MI) was induced by permanent laeft anterior descending artery (LAD) ligation
Interventions:
Immediately after the induction of MI, MSCs preconditioned with either AdLacz or AdTrx1 were administered at 4 sites in the border zone around the infarction
Results:
We observed increased capillary density (2450±107.2 vs.1541±177.8 & 2026±202; counts/mm2)(60d after MI) in the MTRXMI compared to both CMI and MLZMI. Western blot analysis 4d after MI showed increased expression of HSPA12B (HSP70 family member) and VEGF in MTRXMI compared to CMI. Echocardiography (60d after MI) showed increased ejection fraction (50 vs. 31%) and fractional shortening (27 vs. 16%) in the MTRXMI compared to CMI group. Myocardial fibrosis was less extensive in the MTRXMI group (4.8%) compared to CMI group (16.6%). Immunohistochemistry confirmed increased intercellular connection by measuring connexin-43 in the treatment group
Conclusions:
Our approach of Trx1 engineered MSC therapy may prove to be a strategic therapeutic modality in the treatment of cardiac failure by inducing HSPA12B and VEGF expression, neovessel formation, reducing fibrosis and by increasing functional recovery in the rat MI model