Zhang Bo, Adesanya T M Ayodele, Zhang Li, Xie Nanzi, Chen Zhishui, Fu Minghuan, Zhang Jie, Zhang Jian, Tan Tao, Kilic Ahmet, Li Zhihong, Zhu Hua, Xie Xiaoyun
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Physiol Biochem. 2014;34(6):1998-2006. doi: 10.1159/000366395. Epub 2014 Nov 26.
Peripheral artery disease (PAD) is a major health burden in the world. Stem cell-based therapy has emerged as an attractive treatment option in regenerative medicine. In this study, we sought to test the hypothesis that stem cell-based therapy can ameliorate ischemia induced limb injury.
We isolated mesenchymal stem cells derived from human placentas (PMSCs) and intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs reduced acute muscle fibers apoptosis induced by ischemia.
PMSC treatment significantly enhanced regeneration of the injured hind limb by reducing fibrosis and enhancing running capacity when the animals were subjected to treadmill training. Mechanistically, injected PMSCs can modulate acute inflammatory responses by reducing neutrophil and macrophage infiltration following limb ischemia. ELISA assays further confirmed that PMSC treatment can also reduce pro-inflammatory cytokines, TNF-α and IL-6, and enhance anti-inflammatory cytokine, IL-10 at the injury sites.
Taken together, our results demonstrated that PMSCs can be a potential effective therapy for treatment of PAD via immunomodulation.
外周动脉疾病(PAD)是全球主要的健康负担。基于干细胞的疗法已成为再生医学中一种有吸引力的治疗选择。在本研究中,我们试图验证基于干细胞的疗法可改善缺血诱导的肢体损伤这一假说。
我们分离了源自人胎盘的间充质干细胞(PMSCs),并将其肌肉内移植到受伤的后肢。PMSCs治疗减少了缺血诱导的急性肌纤维凋亡。
当动物接受跑步机训练时,PMSC治疗通过减少纤维化和增强跑步能力,显著促进了受伤后肢的再生。从机制上讲,注射的PMSCs可通过减少肢体缺血后中性粒细胞和巨噬细胞浸润来调节急性炎症反应。ELISA分析进一步证实,PMSC治疗还可减少损伤部位的促炎细胞因子TNF-α和IL-6,并增强抗炎细胞因子IL-10。
综上所述,我们的结果表明,PMSCs通过免疫调节可能是治疗PAD的一种潜在有效疗法。