Increased Myocardial Retention of Mesenchymal Stem Cells Post-MI by Pre-Conditioning Exercise Training

• DOI: 10.1007/s12015-020-09970-z
• Publication Date: 2020-04-18T09:02:29Z
• Authors: Stella Souza Vieira; Ednei Luiz Antonio; Brunno Lemes de Melo; Luís Felipe Neves...; Eduardo Tadeu San...; Regiane Feliciano; Fabio Luiz Navarr...; Daniele de Paula ...; Carlos Alberto Bu...; José Antônio Silva; Paulo José Ferrei...; Andrey Jorge Serra
• Keywords: Inflammation; Heart Ventricles; Myocardium; Myocardial Infarction; Mesenchymal Stem Cells; Kaplan-Meier Estimate; Survival Analysis; Rats, Inbred F344; 03 medical and health sciences; 0302 clinical medicine; Physical Conditioning, Animal; Animals; Female; Ischemic Preconditioning

Stem cell (SC) therapy is a promising approach to improve post-myocardial infarction (MI) cardiac remodeling, but the proinflammatory microenvironment may lead to SC loss and, therefore, may have a negative impact on therapy. It appears that exercise training (ET) improves myocardial microenvironment for SC transplantation. Therefore, we tested the effect of ET on post-infarction retention of adipose-derived SCs (ADSCs) and its combined effects on the inflammatory microenvironment. Fischer-344 female rats were randomized to one of the following groups: Sham; sedentary coronary occlusion who did not receive ADSCs (sMI); sedentary coronary occlusion who received ADSCs; exercise coronary occlusion who received ADSCs. Rats were trained nine weeks prior to MI, followed by ADSCs transplantation. The MI led to left ventricle (LV) dilation and dysfunction, myocardial hypertrophy and fibrosis, and increased proinflammatory profile compared to Sham rats. Conversely, ADSCs transplanted rats exhibited, better morphological and functional LV parameters; inhibition of myocardial hypertrophy and fibrosis; and attenuation of proinflammatory cytokines (interleukins 1β and 10, tumor necrosis factor α, and transforming growth factor β) in the myocardium compared to sMI rats. Interestingly, ET enhanced the effect of ADSCs on interleukin 10 expression. There was a correlation between cytokine expression and myocardial ADSCs retention. The. ET enhanced the beneficial effects of ADSCs in infarcted myocardium, which was associated with higher ADSCs retention. These findings highlight the importance of ET in myocardial retention of ADSCs and attenuation of cardiac remodeling post-infarction. Cytokine analysis suggests improvement in ET-linked myocardial microenvironment based on its anti-inflammatory action.