Protective effect of adipose-derived stromal cell-secretome attenuate autophagy induced by liver ischemia-reperfusion and partial hepatectomy.
Protective effect of adipose-derived stromal cell-secretome attenuate autophagy induced by liver ischemia-reperfusion and partial hepatectomy.
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DOI：
10.1186/s13287-022-03109-2
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发表时间：
2022-08-20
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
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脂肪间充质基质细胞（ADSC）的治疗作用可能主要是通过其旁分泌作用介导的。 ADSC 分泌组可以改善肝脏缺血再灌注损伤 (IRI)。我们从肝脏IRI诱导的过度肝细胞自噬的角度探讨了ADSC分泌组的治疗作用。我们采用腹腔镜技术建立了小型猪肝缺血再灌注（I/R）和肝切除模型，并在术后立即将 ADSC 和 ADSC 分泌组移植到肝实质中。通过组织病理学检查和评估相关细胞因子和其他因素来评估肝损伤和肝细胞自噬。结果表明，ADSC-分泌组减轻了IRI后肝组织的病理变化和肝细胞的微观结构损伤。此外，自噬相关标志物（包括 Beclin-1、ATG5、ATG12 和 LC3II/LC3I）的表达水平在吞噬泡扩张过程中下降，而 p62 的表达水平增加。此外，与自噬抑制途径磷脂酰肌醇-3-激酶/Akt/雷帕霉素哺乳动物靶标（PI3K/Akt/mTOR）相关的标志物（包括 PI3K、Akt 和 mTOR）的表达水平增加。 ADSC 分泌组通过抑制自噬来减轻肝脏 I/R 和肝切除术引起的肝损伤，这可能是通过激活 PI3K/Akt/mTOR 信号通路介导的。此外，ADSC与ADSC分泌组在肝细胞自噬的调节方面没有显着差异。因此，ADSCs可能通过旁分泌作用改善肝I/R和肝切除术中过度自噬引起的肝细胞损伤。我们的研究结果为无细胞产品的治疗潜力提供了新的见解，它可以取代肝病的细胞疗法。在线版本包含可在 10.1186/s13287-022-03109-2 获取的补充材料。
The therapeutic effects of adipose-derived mesenchymal stromal cells (ADSCs) may be mainly mediated by their paracrine effects. The ADSC-secretome can ameliorate hepatic ischemia–reperfusion injury (IRI). We explored the therapeutic effect of the ADSC-secretome from the perspective of excessive hepatocyte autophagy induced by hepatic IRI. We established a miniature pig model of hepatic ischemia–reperfusion (I/R) and hepatectomy using a laparoscopic technique and transplanted ADSCs and the ADSC-secretome into the liver parenchyma immediately after surgery. Liver injury and hepatocyte autophagy were evaluated by histopathological examination and assessment of relevant cytokines and other factors. The results showed that the ADSC-secretome alleviated the pathological changes of liver tissue and the microstructural damage of hepatocytes after IRI. Moreover, the expression levels of autophagy-related markers including Beclin-1, ATG5, ATG12, and LC3II/LC3I decreased, whereas those of p62 increased during phagophore expansion. Furthermore, the expression levels of markers related to the autophagy inhibition pathway phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR), including PI3K, Akt, and mTOR, increased. The ADSC-secretome attenuates hepatic I/R and hepatectomy-induced liver damage by inhibiting autophagy, which is possibly mediated by activation of the PI3K/Akt/mTOR signaling pathway. In addition, there was no significant difference between ADSCs and the ADSC-secretome in the regulation of hepatocyte autophagy. Therefore, ADSCs may improve the excessive autophagy-induced injury of hepatocytes in hepatic I/R and hepatectomy through paracrine effect. Our findings provide new insight into the therapeutic potential of cell-free products, which could replace cell therapy in liver diseases. The online version contains supplementary material available at 10.1186/s13287-022-03109-2.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
脂肪干细胞减轻猪缺血再灌注和腹腔镜肝切除术诱导的肝细胞凋亡
影响因子：
4.6
作者：
Ge Y;Zhang Q;Li H;Bai G;Jiao Z;Wang H
通讯作者：
Wang H
影响因子：
1.8
作者：
Zhang H;Liu T;Wang Y;Liu HF;Zhang JT;Wu YS;Lei L;Wang HB
通讯作者：
Wang HB
DOI：
10.1038/nrm3735
发表时间：
2014-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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综述：脂肪干细胞在皮肤伤口愈合和再生中的治疗潜力
影响因子：
7.5
作者：
Li P;Guo X
通讯作者：
Guo X