Laboratory of Physiology and Cardiac Pathophysiology, Department of Medicine, Federal University of São Paulo, SP, São Paulo, Brazil.
Cummings Tufts Veterinary Medical Center, Tufts University, North Graafton, MA, USA.
Stem Cell Rev Rep. 2020 Aug;16(4):730-741. doi: 10.1007/s12015-020-09970-z.
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.
干细胞（SC）疗法是改善心肌梗死后心脏重构的一种很有前途的方法，但促炎微环境可能导致 SC 丢失，因此可能对治疗产生负面影响。运动训练（ET）似乎改善了 SC 移植的心肌微环境。因此，我们测试了 ET 对心肌梗死后脂肪来源干细胞（ADSCs）保留的影响及其对炎症微环境的综合影响。雌性 Fischer-344 大鼠随机分为以下几组：Sham；不接受 ADSCs 的安静性冠状动脉闭塞（sMI）；接受 ADSCs 的安静性冠状动脉闭塞；接受 ADSCs 的运动性冠状动脉闭塞。大鼠在 MI 前进行了九周的训练，然后进行 ADSCs 移植。MI 导致左心室（LV）扩张和功能障碍、心肌肥大和纤维化，并导致与 Sham 大鼠相比促炎谱增加。相反，与 sMI 大鼠相比，接受 ADSCs 移植的大鼠表现出更好的 LV 形态和功能参数；抑制心肌肥大和纤维化；以及减弱心肌中的促炎细胞因子（白细胞介素 1β 和 10、肿瘤坏死因子 α 和转化生长因子 β）。有趣的是，ET 增强了 ADSCs 对白细胞介素 10 表达的影响。细胞因子表达与心肌中 ADSCs 的保留之间存在相关性。ET 增强了 ADSCs 在梗死心肌中的有益作用，这与更高的 ADSCs 保留有关。这些发现强调了 ET 在心肌中保留 ADSCs 和减轻梗死后心脏重构中的重要性。细胞因子分析表明，基于其抗炎作用，ET 改善了与心肌相关的微环境。
