Meng Xin, Li Jianping, Yu Ming, Yang Jian, Zheng Minjuan, Zhang Jinzhou, Sun Chao, Liang Hongliang, Liu Liwen
Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
J Cell Physiol. 2018 Jan;233(1):587-595. doi: 10.1002/jcp.25919. Epub 2017 May 19.
Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI.
间充质干细胞(MSC)对心肌梗死(MI)患者具有治疗潜力,这一点已广为人知。此外,白细胞介素-10(IL10)可通过抑制炎症来减轻心肌梗死。因此,将MSC植入与IL10递送相结合可能会带来更多益处,以改善心肌梗死后的心脏损伤。在此,我们通过腺病毒转导在骨髓来源的MSC中建立了IL10的过表达。检测了体外缺血刺激下的细胞活力、凋亡和IL10分泌情况。此外,将MSC移植到心肌梗死大鼠模型的受损心脏中。在诱导心肌梗死后四周,评估心肌梗死情况、心脏功能、凋亡细胞和炎症细胞因子。在体外氧-葡萄糖剥夺(OGD)刺激下,MSC中IL10的过表达(Ad.IL10-MSC)增强了细胞活力,减少了凋亡,并增加了IL10分泌。同样,与单独给予MSC或IL10治疗相比,将Ad.IL10-MSCs植入心肌梗死动物体内可使心肌梗死面积、心脏损伤和细胞凋亡的减少更为明显。此外,Ad.IL10-MSC治疗在全身和局部炎症的减轻方面最为显著。IL10过表达和MSC可能发挥协同抗炎作用,以减轻心肌梗死后的心脏损伤。