Dataset Information

Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

ABSTRACT: Although stem cells are promising tools for the treatment of arthritis, their therapeutic effects remain controversial. In this study, we investigated the therapeutic properties of interleukin (IL)-10-overexpressing human amniotic mesenchymal stem cells (AMMs) generated via gene editing in a collagen-induced mouse model. IL-10 was inserted into the genomic loci of AMMs via transcription activator-like effector nucleases. In vitro immunomodulatory effects of IL-10-overexpressing AMMs (AMM/I) were evaluated and their anti-arthritogenic properties were determined in collagen-induced arthritis (CIA) mice. Transplantation of AMM/I attenuates CIA progression. In addition, the regulatory T cell population was increased, while T helper-17 cell activation was suppressed by AMM/I administration in CIA mice. Consistently, AMM/I injection increased proteoglycan expression, while reducing inflammation and the expression levels of the pro-inflammatory factors, IL-1 β, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor- α, in joint tissues. In conclusion, use of IL-10-edited human AMM/I may be a novel therapeutic strategy for the treatment of arthritis.

SUBMITTER: Chae DS

PROVIDER: S-EPMC9320257 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

Chae Dong-Sik DS Park Young-Jin YJ Kim Sung-Whan SW

International journal of molecular sciences 20220718 14

Although stem cells are promising tools for the treatment of arthritis, their therapeutic effects remain controversial. In this study, we investigated the therapeutic properties of interleukin (IL)-10-overexpressing human amniotic mesenchymal stem cells (AMMs) generated via gene editing in a collagen-induced mouse model. IL-10 was inserted into the genomic loci of AMMs via transcription activator-like effector nucleases. In vitro immunomodulatory effects of IL-10-overexpressing AMMs (AMM/I) were ...[more]

PMID: 35887258

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Project description:Although most bone fractures typically heal without complications, a small proportion of patients (≤10%) experience delayed healing or potential progression to non-union. Interleukin-1 (IL-1β) plays a crucial role in fracture healing as an early driver of inflammation. However, the effects of IL-1β can impede the healing process if they persist long after the establishment of a fracture hematoma, making it a promising target for novel therapies. Accordingly, the overall objective of this study was to develop a novel gene-based therapy that mitigates the negative effects of IL-1β-driven inflammation while providing a structural template for new bone formation. A collagen-hydroxyapatite scaffold (CHA) was used as a platform for the delivery of nanoparticles composed of pDNA, encoding for IL-1 receptor antagonist (IL-1Ra), complexed to the robust non-viral gene delivery vector, polyethyleneimine (PEI). Utilizing pDNA encoding for Gaussia luciferase and GFP as reporter genes, we found that PEI-pDNA nanoparticles induced a transient gene expression profile in rat bone marrow-derived mesenchymal stromal cells (BM-MSCs), with a transfection efficiency of 14.8 ± 1.8% in 2D. BM-MSC viability was significantly affected by PEI-pDNA nanoparticles as evaluated using CellTiter Blue; however, after 10 days in culture this effect was negligible. Transfection with PEI-pIL-1Ra nanoparticles led to functional IL-1Ra production, capable of antagonizing IL-1β-induced expression of secreted embryonic alkaline phosphatase from HEK-Blue-IL-1β reporter cells. Sustained treatment with IL-1β (0.1, 1, and 10 ng/ml) had a dose-dependent negative effect on BM-MSC osteogenesis, both in terms of gene expression (Alpl and Ibsp) and calcium deposition. BM-MSCs transfected with PEI-IL-1Ra nanoparticles were found to be capable of overcoming the inhibitory effects of sustained IL-1β (1 ng/ml) treatments on in vitro osteogenesis. Ultimately, IL-1Ra gene-activated CHA scaffolds supported mineralization of BM-MSCs under chronic inflammatory conditions in vitro, demonstrating potential for future therapeutic applications in vivo.

Dataset Information

Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

Publications

Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

Similar Datasets

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