Department of Cardiology, Qingdao Municipal Hospital, Qingdao 266000, Shandong, China.
Department of Cardiology, Affiliated Hospital of Hebei University, Baoding 071000, Hebei, China.
Int Immunopharmacol. 2020 Mar;80:106207. doi: 10.1016/j.intimp.2020.106207. Epub 2020 Jan 17.
Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. It has been demonstrated that the induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, represents a novel source for cell therapy in myocardial infarction. However, whether the iCS could also be applied to treat MI-RI remains unclear. Thus, we investigated the therapeutic application of iCS in the mice model MI-RI.
The mice model of MI-RI was established and the iCS cells were transplanted to the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA).
The LV function was significantly improved after the iCS transplantation when compared to the vehicle control group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS transplantation. The protein levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were down-regulated by the iCS transplantation while the IL-10 was up-regulated. The anti-inflammatory factor IL-10 was found to be expressed and secreted by the iCS cells and knocking down the IL-10 in iCS would significantly impair the therapeutic effects of iCS in the mice model of MI-RI.
The present study indicated that the iCS had therapeutic effects on the mice model of MI-RI through secreting the IL-10.
心肌缺血再灌注损伤（MI-RI）具有许多不良并发症，死亡率很高。已经证明，通过体细胞核移植技术从成人皮肤成纤维细胞诱导产生的心肌球体（iCS）是心肌梗死细胞治疗的一种新来源。然而，iCS 是否也可用于治疗 MI-RI 尚不清楚。因此，我们研究了 iCS 在 MI-RI 小鼠模型中的治疗应用。
建立 MI-RI 小鼠模型，并通过尾静脉注射将 iCS 细胞移植到小鼠体内。通过胸骨旁长轴超声心动图评估左心室（LV）尺寸和 LV 压力-容积测量。通过组织学分析确定梗死面积。并通过酶联免疫吸附试验（ELISA）分析炎症反应。
与载体对照组相比，iCS 移植后 LV 功能明显改善，包括收缩末期压力和 dP/dtMax。此外，iCS 移植后梗死面积明显减小。iCS 移植后促炎细胞因子（包括肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β））的蛋白水平下调，而白细胞介素-10（IL-10）上调。发现 iCS 细胞表达和分泌抗炎因子 IL-10，敲低 iCS 中的 IL-10 会显著损害 iCS 在 MI-RI 小鼠模型中的治疗效果。
本研究表明，iCS 通过分泌 IL-10 对 MI-RI 小鼠模型具有治疗作用。
