TGF‐β1 overexpressing human MSCs generated using gene editing show robust therapeutic potential for treating collagen‐induced arthritis
| Autor: | Ju Hye Han, Dong-Sik Chae, Young-Jin Park, Sung-Whan Kim |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0206 medical engineering Population Biomedical Engineering Medicine (miscellaneous) Arthritis 02 engineering and technology Mesenchymal Stem Cell Transplantation T-Lymphocytes Regulatory Immunomodulation Transforming Growth Factor beta1 Biomaterials Cell therapy Mice 03 medical and health sciences Transcription Activator-Like Effector Nucleases medicine Animals Humans Amnion education 030304 developmental biology Gene Editing 0303 health sciences education.field_of_study Chemistry Mesenchymal stem cell Mesenchymal Stem Cells medicine.disease Arthritis Experimental 020601 biomedical engineering Reverse transcription polymerase chain reaction Disease Models Animal Gene Expression Regulation Disease Progression Cancer research Th17 Cells Joints Tumor necrosis factor alpha Cell activation Chondrogenesis Transforming growth factor |
| Zdroj: | Journal of Tissue Engineering and Regenerative Medicine. 15:513-523 |
| ISSN: | 1932-7005 1932-6254 |
| Popis: | Transforming growth factor β (TGF-β plays a pivotal role in cartilage differentiation and other functions of mesenchymal stem cells (MSCs). In this study, we investigated the therapeutic potential of TGF-β1 overexpressing amniotic MSCs (AMMs) generated using gene editing in a mouse model of damaged cartilage. The TGF-β1 gene was inserted into a safe harbor genomic locus in AMMs using transcription activator-like effector nucleases (TALENs). The chondrogenic properties of TGF-β1-overexpressing AMMs (AMM/T) were characterized using reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and histological analysis, and their therapeutic effects were evaluated in mouse model of collagen-induced arthritis (CIA). AMM/T expressed cartilage-specific genes and showed intense Safranin O and Alcian blue staining. Further, injecting AMM/T attenuated CIA progression compared with AMM injection, and increased the regulatory T (Treg) cell population, while suppressing T helper (Th)17 cell activation in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/T injected CIA mice compared with their AMM injected counterparts. In conclusion, genome-edited AMMs overexpressing TGF-β1 may be a novel and alternative therapeutic option for protecting cartilage and treating inflammatory joint arthritis. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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