Adipose-Derived Stem Cells Protect Ischemia-Reperfusion and Partial Hepatectomy by Attenuating Endoplasmic Reticulum Stress

Jiao, Zhen; Liu, Xiaoning; Ma, Yajun; Ge, Yansong; Zhang, Qianzhen; Liu, Boyang; Wang, Hongbin

doi:10.3389/fcell.2020.00177

Cited by 28 publications

(24 citation statements)

References 62 publications

(63 reference statements)

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“…The ASCs successfully differentiated into adipocytes, osteoblasts and hepatocytes in suitable media. We have previously described the isolation, culture and identification of ASCs [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection

Jiao

Zhang

et al. 2021

Stem Cell Res Ther

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Background Hepatic ischaemia-reperfusion injury (HIRI) is inevitable in complicated liver surgery and is a major factor leading to postoperative complications and liver dysfunction. Studies have shown that the paracrine mechanisms of stem cell may be essential to tissue repair and functional improvement after transplantation. However, the role of the adipose-derived mesenchymal stem cell secretome (ASC-secretome) in liver regeneration in large animals remains to be determined. Methods Twenty-four miniature pigs were subjected to laparoscopic liver ischaemia-reperfusion combined with partial hepatectomy and divided into the following four groups: the saline group, the DMEM group, the ASC group and the ASC-secretome group. Serum and liver tissue samples were collected before the operation and at 1, 3 and 7 days after the operation, and changes in tissue pathology, serum inflammation, liver function, angiogenesis-related factors and liver tissue regeneration-related genes and proteins were evaluated. Results Detailed histological analysis showed that ASCs and the ASC-secretome changed pathological damage to liver tissue after liver ischaemia-reperfusion combined with partial hepatectomy (1 and 3 days: p < 0.01). Compared with the saline and DMEM control groups, the ASC-secretome group had significantly reduced expression levels of ALP (1 and 3 days: p < 0.05), ALT (1 day: p < 0.01; 3 days: p < 0.05) and AST (1 and 3 days: p < 0.01), which promoted the recovery of liver function. Moreover, detection of the expression levels of TNF-α and IL-1β (1 day: p < 0.01; 3 days: p < 0.05), IL-6 (1 and 3 days: p < 0.05) and IL-10 (1 and 3 days: p < 0.01) in serum confirmed that the ASC-secretome had obvious anti-inflammatory effects. In addition, the ASC-secretome increased the expression levels of ANG-1 (3 days: p < 0.01), ANG-2 (3 and 7 days: p < 0.01) and VEGF (1 and 7 days: p < 0.05; 3 days: p < 0.01) and promoted angiogenesis during liver regeneration. Moreover, it promoted the mRNA expression of HGF and Cyclin D1 (1 and 3 days: p < 0.01); increased the levels of p-STAT3 (1 and 3 days: p < 0.01), PCNA and Ki67 (1 and 3 days: p < 0.01; 7 days: p < 0.05); inhibited the negative feedback of SOCS3 (1 and 3 days: p < 0.01); and decreased the mRNA expression of TGF-β (3 days: p < 0.01). The cytokines and growth factors detected in the ASC-secretome included TNF-α, IL-6, IL-1β, ANG-1, ANG-2, VEGF and b-FGF. Conclusion The ASC-secretome alleviates the inflammatory response induced by ischaemia-reperfusion combined with partial hepatectomy in miniature pigs and promotes liver regeneration.

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“…The ASCs successfully differentiated into adipocytes, osteoblasts and hepatocytes in suitable media. We have previously described the isolation, culture and identification of ASCs [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection

Jiao

Zhang

et al. 2021

Stem Cell Res Ther

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“…The ER is the site of protein synthesis, posttranslational modification, folding, and trafficking. ICH can cause ER stress (ERS), which is characterized by protein misfolding, accumulation of abnormal proteins, and Ca 2+ imbalance, all of which trigger the unfolded protein response (UPR) [ 24 ]. Glutamate excitotoxicity and the inflammatory response can result in ERS.…”

Section: Ros Production After Ichmentioning

confidence: 99%

Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

Yao

Bai

Wang

2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress (OS) is induced by the accumulation of reactive oxygen species (ROS) following intracerebral hemorrhage (ICH) and plays an important role in secondary brain injury caused by the inflammatory response, apoptosis, autophagy, and blood-brain barrier (BBB) disruption. This review summarizes the current state of knowledge regarding the pathogenic mechanisms of brain injury after ICH, markers for detecting OS, and therapeutic strategies that target OS to mitigate brain injury.

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“…digested with 0.01% collagenase type I, and resuspended in L-DMEM supplemented with 10% FBS (Clark, United States), 100 µg/ml streptomycin, 1 µg/ml penicillin and 2 mM L-glutamine (Solarbio, China). Finally, the cells were cultured in an incubator at 37℃ with 5% CO2 [24]. The ADSCs from the fourth passages were seeded in T75 culture asks (Corning, United States), and then lled, discarded the original culture medium, washed with PBS, and replaced with starvation culture medium.…”

Section: Culture Of Adscs and Preparation Of Adsc-cmmentioning

confidence: 99%

“…Our ndings provide a new insight into the therapeutic potential of cell-free products instead of cell transplantation in liver diseases. 24 Guangxi Bama miniature pigs aged 4-6 months, weighing 20-30 kg, half male and half female, were provided by the College of College of Veterinary Medicine (Harbin, China). All of them were raised under the same conditions, and randomly divided into four groups with 6 animals in each group.…”

Section: Introductionmentioning

confidence: 99%

Secretome of Adipose-Derived Stem Cells Protect Ischemia-Reperfusion and Partial Hepatectomy by Attenuating Autophagy

Jiao

Liu

et al. 2020

Preprint

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Background: The therapeutic effects of adipose-derived mesenchymal stem cells (ADSCs) may mainly come from their paracrine effects. ADSCs can ameliorate hepatic ischemia-reperfusion injury (IRI). We explored the therapeutic effect of ADSCs secretome from the perspective of excessive autophagy of hepatocytes induced by hepatic IRI.Methods: In this study, we established a miniature pig model of hepatic ischemia-reperfusion (I/R) combined with hepatectomy using laparoscopic technique, and transplanted ADSCs and adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) into the liver parenchyma immediately after surgery. Histopathological and TEM examinations were performed on liver tissue samples collected. We analyzed the roles of ADSC-CM and ADSCs in autophagy by RT-qPCR, western-blot and immunohistochemistry. Results: The results showed that ADSCs and ADSC-CM all alleviated the pathological changes of liver tissue and the microstructural damage of hepatocytes after IRI. Moreover, the expression of the critical markers of autophagy including Beclin-1, ATG5, ATG12 and LC3II all decreased, whereas expression of p62 increased. And the data of autophagy regulation between ADSC-CM and ADSCs showed no significant difference. Finally, we found that ADSC-CM possibly inhibited autophagy by regulating the PI3K/Akt/mTOR pathway.Conclusion: ADSC-CM can ameliorate excessive autophagy injury in hepatic I/R combined with partial hepatectomy, which is possibly involved with the modulation of the PI3K/Akt/mTOR signaling pathway. There was no significant difference between ADSCs and ADSC-CM in the regulation of hepatocyte autophagy. Therefore, ADSCs may improve the excessive autophagy injury of hepatocytes in hepatic I/R combined with hepatectomy through paracrine effect, thus protecting the liver and promoting the liver tissue repair.

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Adipose-Derived Stem Cells Protect Ischemia-Reperfusion and Partial Hepatectomy by Attenuating Endoplasmic Reticulum Stress

Cited by 28 publications

References 62 publications

The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection

The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection

Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

Secretome of Adipose-Derived Stem Cells Protect Ischemia-Reperfusion and Partial Hepatectomy by Attenuating Autophagy

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