Integrated metabolomics and phosphoproteomics reveal the protective role of exosomes from human umbilical cord mesenchymal stem cells in naturally aging mouse livers

Ling, Mingying; Tang, Cong-min; Yang, Xuechun; Yu, Na; Song, Yi-ping; Ding, Wen-jing; Sun, Yan; Yan, Rong; Wang, Shaopeng; Li, Xuehui; Gao, Hai-qing; Zhang, Zhen; Xing, Yanqiu

doi:10.1016/j.yexcr.2023.113566

Cited by 8 publications

(2 citation statements)

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“…However, the mechanisms of the attenuation of lipotoxicity in hepatocytes induced by MSCs remain poorly understood. Using a mouse natural aging model, Ling et al [262] demonstrated that hUCMSC-exos significantly reduced aging markers and genomic instability in aging livers. Metabolome studies found that hUCMSC-exos reduced lipids associated with lipotoxicity and inflammation, including saturated glycerophospholipids, palmitoyl-glycerols, and eicosanoid derivatives.…”

Section: Mscs Protection From Lypotoxicity and Er Stressmentioning

confidence: 99%

“…Using phosphoproteomics approaches, the authors also showed a decrease in the phosphorylation of the metabolic enzyme propionate-CoA ligase. In addition, it was shown that hUCMSC-exos significantly reduced the phosphorylation of proteins involved in nuclear transport and cancer signaling in hepatocytes, including heat shock protein HSP90-beta (Hsp90ab1) and nucleoprotein TPR, and increased the phosphorylation of proteins involved in the intercellular communication, such as calnexin and PDZ domain-containing protein 8 (Pdzd8) [262].…”

Section: Mscs Protection From Lypotoxicity and Er Stressmentioning

confidence: 99%

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The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress

Kholodenko,

Yarygin

2023

IJMS

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Liver diseases, characterized by high morbidity and mortality, represent a substantial medical problem globally. The current therapeutic approaches are mainly aimed at reducing symptoms and slowing down the progression of the diseases. Organ transplantation remains the only effective treatment method in cases of severe liver pathology. In this regard, the development of new effective approaches aimed at stimulating liver regeneration, both by activation of the organ’s own resources or by different therapeutic agents that trigger regeneration, does not cease to be relevant. To date, many systematic reviews and meta-analyses have been published confirming the effectiveness of mesenchymal stromal cell (MSC) transplantation in the treatment of liver diseases of various severities and etiologies. However, despite the successful use of MSCs in clinical practice and the promising therapeutic results in animal models of liver diseases, the mechanisms of their protective and regenerative action remain poorly understood. Specifically, data about the molecular agents produced by these cells and mediating their therapeutic action are fragmentary and often contradictory. Since MSCs or MSC-like cells are found in all tissues and organs, it is likely that many key intercellular interactions within the tissue niches are dependent on MSCs. In this context, it is essential to understand the mechanisms underlying communication between MSCs and differentiated parenchymal cells of each particular tissue. This is important both from the perspective of basic science and for the development of therapeutic approaches involving the modulation of the activity of resident MSCs. With regard to the liver, the research is concentrated on the intercommunication between MSCs and hepatocytes under normal conditions and during the development of the pathological process. The goals of this review were to identify the key factors mediating the crosstalk between MSCs and hepatocytes and determine the possible mechanisms of interaction of the two cell types under normal and stressful conditions. The analysis of the hepatocyte–MSC interaction showed that MSCs carry out chaperone-like functions, including the synthesis of the supportive extracellular matrix proteins; prevention of apoptosis, pyroptosis, and ferroptosis; support of regeneration; elimination of lipotoxicity and ER stress; promotion of antioxidant effects; and donation of mitochondria. The underlying mechanisms suggest very close interdependence, including even direct cytoplasm and organelle exchange.

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Section: Mscs Protection From Lypotoxicity and Er Stressmentioning

confidence: 99%

Section: Mscs Protection From Lypotoxicity and Er Stressmentioning

confidence: 99%