Effect of conditioned medium from adipose derived mesenchymal stem cells on endoplasmic reticulum stress and lipid metabolism after hepatic ischemia reperfusion injury and hepatectomy in swine

Zhang, Qianzhen; Liu, Xiaoning; Piao, Chenxi; Jiao, Zhen; Ma, Yajun; Wang, Yue; Liu, Tao; Xu, Jiayuan; Wang, Hongbin

doi:10.1016/j.lfs.2021.120212

Cited by 10 publications

(6 citation statements)

References 52 publications

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“…This suggested that triglyceride synthesis protected from liver damage [ 55 ]. Similarly, MSC improved lipid metabolism in the pig liver after ischemia reperfusion injury and hepatectomy by increasing, in addition to others, hepatic VLDL [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stromal Cells Resolve Lipid Load in High Fat Diet-Induced Non-Alcoholic Steatohepatitis in Mice by Mitochondria Donation

Nickel

Christ

Schmidt

et al. 2022

Cells

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Mesenchymal stromal cells (MSC) increasingly emerge as an option to ameliorate non-alcoholic steatohepatitis (NASH), a serious disease, which untreated may progress to liver cirrhosis and cancer. Before clinical translation, the mode of action of MSC needs to be established. Here, we established NASH in an immune-deficient mouse model by feeding a high fat diet. Human bone-marrow-derived MSC were delivered to the liver via intrasplenic transplantation. As verified by biochemical and image analyses, human mesenchymal stromal cells improved high-fat-diet-induced NASH in the mouse liver by decreasing hepatic lipid content and inflammation, as well as by restoring tissue homeostasis. MSC-mediated changes in gene expression indicated the switch from lipid storage to lipid utilization. It was obvious that host mouse hepatocytes harbored human mitochondria. Thus, it is feasible that resolution of NASH in mouse livers involved the donation of human mitochondria to the mouse hepatocytes. Therefore, human MSC might provide oxidative capacity for lipid breakdown followed by restoration of metabolic and tissue homeostasis.

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Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stromal Cells Resolve Lipid Load in High Fat Diet-Induced Non-Alcoholic Steatohepatitis in Mice by Mitochondria Donation

Nickel

Christ

Schmidt

et al. 2022

Cells

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“…Z. Zhang, Q. Z. Liu, et al, 2022). Lu et al found that extracellular vesicles derived from ADSCs protect against spinal cord I/R injury by inhibiting ERS (Lu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

Zhang

Piao

et al. 2023

Journal Cellular Physiology

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Hepatic ischemia-reperfusion (I/R) injury commonly occurs during liver surgery.Exosomes from adipose-derived stem cells (ADSCs-exo) induce a hepatoprotective effect during hepatic I/R injury. This study aimed to investigate the possible mechanism by which ADSCs-exo attenuates hepatic I/R injury in rats. Rats were randomly divided into four groups: Sham, I30R + PH, ADSCs, and ADSCs-exo groups. Liver tissues were collected immediately after 24 h of reperfusion for further analyses. The content of inflammatory factors in liver tissue was detected using enzyme-linked immunosorbent assay. The pathological changes in liver tissue were analyzed using HE staining. Transmission electron microscopy was used to visualize the ultrastructural changes of hepatocytes. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of endoplasmic reticulum stress (ERS)-related genes and proteins. Liver histomorphology and hepatocyte ultrastructure changes improved after ADSCs-exo treatment.Moreover, ADSCs-exo treatment significantly downregulated tumor necrosis factorα, interleukin-1β (IL-1β), and IL-6 levels while upregulating IL-10 levels. Western blot analysis suggested that the protein expressions of GRP78, p-PERK, p-eIF2α, p-IRE1α, XBP1s, ATF-6, ATF-4, CHOP, p-JNK, cleaved-Caspase-3, cleaved Caspase-9, and cleaved Caspase-12 significantly decreased after ADSCs-exo treatment. RT-qPCR results demonstrated that mRNA expression of GRP78, IRE1α, XBP1, ATF-6, ATF-4, CHOP, JNK, Caspase-3, Caspase-9, and Caspase-12 markedly reduced after ADSCs-exo treatment. In conclusion, ADSCs-exo protects against hepatic I/R injury after hepatectomy by inhibiting ERS and inflammation. Therefore, ADSCs-exo can be considered as a viable option for the treatment of hepatic I/R injury.

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“…Apoptosis, a crucial role in the cell cycle, is an integral proportion of the biological organisms whatever in physiological or pathological condition, and that is a common pathological characteristic of HIRI (Bi et al, 2019; Xu, Lai, & Hua, 2019). During HIRI, ischemia and hypoxia damage the mitochondrial structure and function in tissue cells, and result in pro‐apoptotic factors enter the cytoplasm to induce hepatocyte apoptosis (Masior & Grąt, 2021; Zhang et al, 2021; Zhang et al, 2022). In this research, MMP was observed via JC‐1 staining and cell apoptosis was observed though TUNEL assay and immunofluorescence staining.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of pinocembrin from Penthorum chinense Pursh on hepatic ischemia reperfusion injury via regulating HMGB1/TLR4 signal pathway

Zhang

et al. 2022

Phytotherapy Research

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Hepatic ischemia–reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H2O2‐induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H2O2 group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl‐2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB‐1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.

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Effect of conditioned medium from adipose derived mesenchymal stem cells on endoplasmic reticulum stress and lipid metabolism after hepatic ischemia reperfusion injury and hepatectomy in swine

Cited by 10 publications

References 52 publications

Human Mesenchymal Stromal Cells Resolve Lipid Load in High Fat Diet-Induced Non-Alcoholic Steatohepatitis in Mice by Mitochondria Donation

Human Mesenchymal Stromal Cells Resolve Lipid Load in High Fat Diet-Induced Non-Alcoholic Steatohepatitis in Mice by Mitochondria Donation

ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

Protective effect of pinocembrin from Penthorum chinense Pursh on hepatic ischemia reperfusion injury via regulating HMGB1/TLR4 signal pathway

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