Combined Therapy with Extracorporeal Shock Wave and Adipose-Derived Mesenchymal Stem Cells Remarkably Improved Acute Ischemia-Reperfusion Injury of Quadriceps Muscle

体外冲击波联合脂肪间充质干细胞治疗显著改善股四头肌急性缺血再灌注损伤

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Abstract

Extracorporeal shock wave (ECSW) and adipose-derived mesenchymal stem cells (ADMSCs) have been recognized to have capacities of anti-inflammation and angiogenesis. We tested the hypothesis that ECSW and ADMSC therapy could attenuate ischemia-reperfusion- (IR-) induced thigh injury (femoral artery tightened for 6 h then the tightness was relieved) in rats. Adult male SD rats (n = 30) were divided into group 1 (sham-control), group 2 (IR), group 3 (IR + ECSW/120 impulses at 0.12 mJ/mm(2) given at 3 h/24 h/72 h after IR), group 4 (allogenic ADMSC/1.2 × 10(6) cell intramuscular and 1.2 × 10(6) cell intravenous injections 3 h after IR procedure), and group 5 (ECSW + ADMSC). At day 7 after the IR procedure, the left quadriceps muscle was harvested for studies. At 18 h after the IR procedure, serum myoglobin/creatine phosphokinase (CPK) levels were highest in group 2, lowest in group 1, and with intermediate values significantly progressively reduced in groups 3 to 5 (all p < 0.0001). By day 5 after IR, the mechanical paw-withdrawal threshold displayed an opposite pattern of CPK (all p < 0.0001). The protein expressions of inflammatory, oxidative-stress, apoptotic, fibrotic, DNA-damaged, and mitochondrial-damaged biomarkers and cellular expressions of inflammatory and DNA-damaged biomarkers exhibited an identical pattern of CPK among the five groups (all p < 0.0001). The microscopic findings of endothelial-cell biomarkers and number of arterioles expressed an opposite pattern of CPK, and the angiogenesis marker was significantly progressively increased from groups 1 to 5, whereas the histopathology showed that muscle-damaged/fibrosis/collagen-deposition areas exhibited an identical pattern of CPK among the five groups (all p < 0.0001). In conclusion, ECSW-ADMSC therapy is superior to either one applied individually for protecting against IR-induced thigh injury.

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