The Effects of Programmed Cell Death of Mesenchymal Stem Cells on the Development of Liver Fibrosis

Abstract

Mesenchymal stem cells have shown noticeable potential for unlimited self-renewal. They can differentiate into specific somatic cells, integrate into target tissues via cell-cell contact, paracrine effects, exosomes, and other processes and then regulate the target cells and tissues. Studies have demonstrated that transplantation of MSCs could decrease the expression and concentration of collagen in the liver, thereby reducing liver fibrosis. A growing body of evidence indicates that apoptotic MSCs could inhibit harmful immune responses and reduce inflammatory responses more effectively than viable MSCs. Accumulating evidence suggests that mitochondrial transfer from MSCs is a novel strategy for the regeneration of various damaged cells via the rescue of their respiratory activities. This study is aimed at reviewing the functions of MSCs and the related roles of the programmed cell death of MSCs, including autophagy, apoptosis, pyroptosis, and ferroptosis, as well as the regulatory pathogenic mechanisms of MSCs in liver fibrosis. Research has demonstrated that the miR-200B-3p gene is differentially expressed gene between LF and normal liver samples, and that the miR-200B-3p gene expression is positively correlated with the degree of liver fibrosis, suggesting that MSCs could inhibit liver fibrosis through pyroptosis. It was confirmed that circulating monocytes could deliver MSC-derived immunomodulatory molecules to different sites by phagocytosis of apoptotic MSCs, thereby achieving systemic immunosuppression. Accordingly, it was suggested that characterization of the programmed cell death-mediated immunomodulatory signaling pathways in MSCs should be a focus of research.

Role of Exosomal Modulation of Macrophages in Liver Fibrosis

“…These exosomes have been found to inhibit TGF-1/SMAD signaling to inhibit LF and stimulate hepatocyte proliferation, leading to a protective effect on hepatocytes. 85 , 88 Similar anti-LF and hepatoprotective and regenerative effects were also observed with exosomes from various sources of MSCs, including bmMSCs, 89 , 90 hucMSCs, 91 , 92 hlMSCs, 93 induced pluripotent MSCs, 94 heMSCs, 95 blood-derived MSCs, 96 and adipose-derived MSCs of adipose origin. 97 Numerous studies have linked the anti-LF impact of macrophages to the exosomes derived from MSCs.…”

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

“…Radiation-induced autophagy may be regulated by modulators such as IL6, IL1, TNFα, IL18, microRNAs like mi-croRNA-7 and microRNA-7-5P, and ROS. Augmentation of autophagy results in increased cervical cancer cell death under radiation (Roy et al, 2022;Wu et al, 2023). Autophagy occurs to maintain stability and promote cell survival against radiation, thus contributing to cells' radioresistance (Lomonaco et al, 2009;Saleh et al, 2022).…”