Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury

Abstract

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.

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

“…Hsiao S T et al detected higher levels of insulin-like growth factor-1, vascular endothelial growth factor-D, and interleukin-8 in the ADSC-secretome compared with those in the secretome of other mesenchymal stromal cell populations, and the ADSC-secretome had more advantages in promoting angiogenesis [ 27 ]. Now, our study has demonstrated that the ADSC-secretome not only reduced the expression levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase and had obvious therapeutic effects, but also attenuated inflammation and activated the STAT3 signaling pathway to promote liver regeneration in a model of hepatic I/R combined with partial hepatectomy [ 28 ]. In this study, we observed that the ADSC-secretome improved the liver damage in a porcine hepatic I/R and hepatectomy model by alleviating hepatocyte autophagy.…”

Bioregenerative Applications of the Human Mesenchymal Stem Cell- Derived Secretome: Part-II

“…Liver Injury [15][16][17][18][19][20][21][22][23][24] Cancer [25,26] Cancer Treatment Injuries [27][28][29] Heart Transplantation [30] Rotator Cuff Injury [31,32] GvHD [33] Wound Healing [34][35][36][37][38][39][40][41][42][43][44][45] Parkinson's Disease [46][47][48][49][50] Alzheimer's Disease [51][52][53][54][55] ALS [56,57] Huntington's Disease [58,59] Niemann-Pick Type C Disease [60] Ocular Injury [61] Lung Injury [62,63] Acute Osseous Injury…”

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

“…MSCs-CM are whole ingredients (secretome) secreted by MSCs during culture; therefore, their efficacy is closer to MSCs than MSCs-exo and MSCs-EV. Jiao et al [75] indicated that MSCs-CM therapy was a viable alternative to MSCs therapy. Daan et al [76] found that MSCs-CM therapy could reduce hepatocyte apoptosis by up to 90%.…”