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

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 bio...

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Main Authors: Zhihui Jiao, Yajun Ma, Yue Wang, Tao Liu, Qianzhen Zhang, Xiaoning Liu, Chenxi Piao, Boyang Liu, Hongbin Wang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/9969372
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author Zhihui Jiao
Yajun Ma
Yue Wang
Tao Liu
Qianzhen Zhang
Xiaoning Liu
Chenxi Piao
Boyang Liu
Hongbin Wang
author_facet Zhihui Jiao
Yajun Ma
Yue Wang
Tao Liu
Qianzhen Zhang
Xiaoning Liu
Chenxi Piao
Boyang Liu
Hongbin Wang
author_sort Zhihui Jiao
collection DOAJ
description 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.
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series Stem Cells International
spelling doaj-art-7c8842f6669e4299817a704fd0a2d8b12025-02-03T01:05:32ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/99693729969372Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy InjuryZhihui Jiao0Yajun Ma1Yue Wang2Tao Liu3Qianzhen Zhang4Xiaoning Liu5Chenxi Piao6Boyang Liu7Hongbin Wang8College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaIschemia-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.http://dx.doi.org/10.1155/2021/9969372
spellingShingle Zhihui Jiao
Yajun Ma
Yue Wang
Tao Liu
Qianzhen Zhang
Xiaoning Liu
Chenxi Piao
Boyang Liu
Hongbin Wang
Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury
Stem Cells International
title Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury
title_full Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury
title_fullStr Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury
title_full_unstemmed Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury
title_short Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury
title_sort protective effect of adipose derived mesenchymal stem cell secretome against hepatocyte apoptosis induced by liver ischemia reperfusion with partial hepatectomy injury
url http://dx.doi.org/10.1155/2021/9969372
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