Protective effect of adipose-derived stromal cell-secretome attenuate autophagy induced by liver ischemia-reperfusion and partial hepatectomy

  • Stem Cell Res Ther. 2022 Aug 20;13(1):427. doi: 10.1186/s13287-022-03109-2.
Yajun Ma  1  2 ,  Zhihui Jiao  1  2 ,  Xiaoning Liu  1  2 ,  Qianzhen Zhang  1  2 ,  Chenxi Piao  1  2 ,  Jiayuan Xu  1  2 ,  Hongbin Wang  3  4
Affiliations
  • 1. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
  • 2. Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, People's Republic of China.
  • 3. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. [email protected].
  • 4. Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, People's Republic of China. [email protected].
PMID: 35987696 DOI: 10.1186/s13287-022-03109-2
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords
ADSC-secretome; Autophagy; IRI; Laparoscopy; Miniature pig.
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