Jiao Zhihui, Ma Yajun, Wang Yue, Liu Tao, Zhang Qianzhen, Liu Xiaoning, Piao Chenxi, Liu Boyang, Wang Hongbin
College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.
Stem Cells Int. 2021 Aug 18;2021:9969372. doi: 10.1155/2021/9969372. eCollection 2021.
Ischemia-reperfusion injury (IRI) is an inevitable complication of liver surgery and liver transplantation. Hepatocyte apoptosis plays a significant role in the pathological process of hepatic IRI. Adipose-derived stem cells (ADSCs) are known to repair and regenerate damaged tissues by producing bioactive factors, including cytokines, exosomes, and extracellular matrix components, which collectively form the secretome of these cells. The aim of this study was to assess the protective effects of the ADSCs secretome after liver ischemia-reperfusion combined with partial hepatectomy in miniature pigs. We successfully established laparoscopic liver ischemia-reperfusion with partial hepatectomy in miniature pigs and injected saline, DMEM, ADSC-secretome, and ADSCs directly into the liver parenchyma immediately afterwards. Both ADSCs and the ADSC-secretome improved the IR-induced ultrastructural changes in hepatocytes and significantly decreased the proportion of TUNEL-positive apoptotic cells along with caspase activity. Consistent with this, P53, Bax, Fas, and Fasl mRNA and protein levels were markedly decreased, while Bcl-2 was significantly increased in the animals treated with ADSCs and ADSC-secretome. Our findings indicate that ADSCs exert therapeutic effects in a paracrine manner through their secretome, which can be a viable alternative to cell-based regenerative therapies.
缺血再灌注损伤（IRI）是肝脏手术和肝移植不可避免的并发症。肝细胞凋亡在肝脏IRI的病理过程中起重要作用。脂肪来源干细胞（ADSCs）已知可通过产生生物活性因子来修复和再生受损组织，这些生物活性因子包括细胞因子、外泌体和细胞外基质成分，它们共同构成了这些细胞的分泌组。本研究的目的是评估在小型猪肝缺血再灌注联合部分肝切除术后ADSCs分泌组的保护作用。我们成功地在小型猪中建立了腹腔镜下肝缺血再灌注联合部分肝切除术，并随后立即将生理盐水、DMEM、ADSC分泌组和ADSCs直接注入肝实质。ADSCs和ADSC分泌组均改善了IR诱导的肝细胞超微结构变化，并显著降低了TUNEL阳性凋亡细胞的比例以及半胱天冬酶活性。与此一致的是，在接受ADSCs和ADSC分泌组治疗的动物中，P53、Bax、Fas和Fasl的mRNA和蛋白水平显著降低，而Bcl-2显著升高。我们的研究结果表明，ADSCs通过其分泌组以旁分泌方式发挥治疗作用，这可能是基于细胞的再生疗法的可行替代方案。
