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Induced pluripotent stem cell-based therapies for organ fibrosis.

ABSTRACT: Fibrotic diseases result in organ remodelling and dysfunctional failure and account for one-third of all deaths worldwide. There are no ideal treatments that can halt or reverse progressive organ fibrosis, moreover, organ transplantation is complicated by problems with a limited supply of donor organs and graft rejection. The development of new approaches, especially induced pluripotent stem cell (iPSC)-based therapy, is becoming a hot topic due to their ability to self-renew and differentiate into different cell types that may replace the fibrotic organs. In the past decade, studies have differentiated iPSCs into fibrosis-relevant cell types which were demonstrated to have anti-fibrotic effects that may have the potential to inform new effective precision treatments for organ-specific fibrosis. In this review, we summarize the potential of iPSC-based cellular approaches as therapeutic avenues for treating organ fibrosis, the advantages and disadvantages of iPSCs compared with other types of stem cell-based therapies, as well as the challenges and future outlook in this field.

SUBMITTER: Cheng W

PROVIDER: S-EPMC10232908 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Induced pluripotent stem cell-based therapies for organ fibrosis.

Cheng Wei W Fan Chengming C Song Qing Q Chen Ping P Peng Hong H Lin Ling L Liu Cong C Wang Bin B Zhou Zijing Z

Frontiers in bioengineering and biotechnology 20230518

Fibrotic diseases result in organ remodelling and dysfunctional failure and account for one-third of all deaths worldwide. There are no ideal treatments that can halt or reverse progressive organ fibrosis, moreover, organ transplantation is complicated by problems with a limited supply of donor organs and graft rejection. The development of new approaches, especially induced pluripotent stem cell (iPSC)-based therapy, is becoming a hot topic due to their ability to self-renew and differentiate i ...[more]

PMID: 37274156

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Project description:Progression of fibrosis and the development of cirrhosis are responsible for the liver related morbidity and mortality associated with chronic liver diseases. There is currently a great unmet need for effective anti-fibrotic strategies. Stem cells play a central role in wound healing responses to restore liver homeostasis following injury. Here we tested the hypothesis that extracellular vesicles (EVs) isolated from induced pluripotent stem cells (iPSC) modulate hepatic stellate cell (HSCs) activation and may have anti-fibrotic effects. Human iPSCs were generated by reprogramming primary skin fibroblasts. EVs were isolated by differential centrifugation, quantified by flow cytometry (FACS) and characterized by dynamic light scattering (DLS) and electron microscopy (TEM). Primary human HSCs were activated with TGFβ (10 ng/mL) and exposed to iPSC-EVs. Efficacy of iPSC-EVs was tested on HSC in vitro and in two murine models of liver injury (CCl4 and bile duct ligation). Characterization of iPSC-derived EVs by flow cytometry identified a large population of EVs released by iPSC, primarily with a diameter of 300 nm and that could be visualized by TEM as round, cup-shaped objects. Fluorescent tracing assays detected iPSC-EVs in HSC cytosol after a short incubation and EV uptake by HSCs resulted in both decrease of pro-fibrogenic markers αSMA, CollagenIα1, Fibronectin and TIMP-1 and HSC pro-fibrogenic responses such as chemotaxis and proliferation. Genomics analyses of iPSC-EV miRNA cargo revealed 22 highly expressed miRNAs, among which miR-92a-3p resulted the most abundant. Transcriptome analysis identified 60 genes down-modulated and 235 up-regulated in TGF-β-primed HSC in presence or absence of iPSC-EVs. Intravenous injection of iPSC-EVs in CCl4 and bile duct ligation-induced liver fibrosis resulted in anti-fibrotic effects at protein and gene levels. Results of this study identify iPSC-EVs as a novel anti-fibrotic approach that may reduce or reverse liver fibrosis in patients with chronic liver disease.

Dataset Information

Induced pluripotent stem cell-based therapies for organ fibrosis.

Publications

Induced pluripotent stem cell-based therapies for organ fibrosis.

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