Chitosan hydrogel incorporated with bone marrow mesenchymal stem cell-derived exosomal TIMP2 to inhibit angiogenesis in cholangiocarcinoma.

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2024-12-18 DOI:10.1016/j.tice.2024.102694

Fei Song, Dan Xu, Jiayin Che, Ming Huang, Hongyang Li

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引用次数: 0

Abstract

Objective: Cholangiocarcinoma (CCA) presents a therapeutic challenge due to its aggressiveness and poor survival rates. This study introduces an approach using tissue inhibitor of metalloproteinase 2 (TIMP2)-enriched bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) encapsulated in chitosan hydrogels (CS), intending to provide novel insight into the CCA treatment.

Methods: BMSC-Exo was characterized by using TEM, nanoparticle tracking analysis, and western blotting. Role of TIMP2 in CCA was explored using bioinformatics analysis. Therapeutic efficacy and mechanisms of BMSC-Exo/CS in CCA were assessed through cell viability tests and colony formation assays. Angiogenic and Wnt/β-catenin signaling pathways-related key factors were detected through RT-qPCR or western blotting.

Results: BMSC-Exo displayed typical cup-shaped morphology and was positive for exosomal markers CD9 and TSG101, but negative for endoplasmic reticulum marker Calnexin, with a diameter of 124.6 nm. BMSC-Exo combined with CS showed synergistic anti-proliferative effects in CCA cells. High-expression TIMP2 samples indicated a better prognosis of CCA patients, and BMSC-Exo/CS increased the TIMP2 expression in CCA cells. Mechanistically, BMSC-Exo/CS TIMP2 overexpression inhibited key factors related to angiogenesis (VEGFA and VEGFR2) and Wnt/β-catenin pathway (β-catenin and c-Myc), thereby reducing CCA cell viability. Notably, these inhibitory effects were reversed by a Wnt signaling agonist (BML-284).

Conclusion: The study validates the therapeutic potential of BMSC-Exo/CS TIMP2 in CCA treatment. This innovative approach targets angiogenesis and Wnt/β-catenin signaling, providing a new avenue for more effective and comprehensive CCA therapies.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.