Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis
Abstract Direct reprogramming has garnered considerable attention due to its capacity to directly convert differentiated cells into desired cells. Fibroblasts are frequently employed in reprogramming studies due to their abundance and accessibility. However, they are also the key drivers in the prog...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-06060-3 |
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| author | Haohui Lin Xia Wang Manhon Chung Sa Cai Yu Pan |
| author_facet | Haohui Lin Xia Wang Manhon Chung Sa Cai Yu Pan |
| author_sort | Haohui Lin |
| collection | DOAJ |
| description | Abstract Direct reprogramming has garnered considerable attention due to its capacity to directly convert differentiated cells into desired cells. Fibroblasts are frequently employed in reprogramming studies due to their abundance and accessibility. However, they are also the key drivers in the progression of fibrosis, a pathological condition characterized by excessive extracellular matrix deposition and tissue scarring. Furthermore, the initial stage of reprogramming typically involves deactivating fibrotic pathways. Hence, direct reprogramming offers a valuable method to regenerate target cells for tissue repair while simultaneously reducing fibrotic tendencies. Understanding the link between reprogramming and fibrosis could help develop effective strategies to treat damaged tissue with a potential risk of fibrosis. This review summarizes the advances in direct reprogramming and reveals their anti-fibrosis effects in various organs such as the heart, liver, and skin. Furthermore, we dissect the mechanisms of reprogramming influenced by fibrotic molecules including TGF-β signaling, mechanical signaling, inflammation signaling, epigenetic modifiers, and metabolic regulators. Innovative methods for fibroblast reprogramming like small molecules, CRISPRa, modified mRNA, and the challenges of cellular heterogeneity and senescence faced by in vivo direct reprogramming, are also discussed. |
| format | Article |
| id | doaj-art-aaffc270813d4997851af046096d1ce2 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-aaffc270813d4997851af046096d1ce22025-08-20T02:01:39ZengBMCJournal of Translational Medicine1479-58762025-02-0123111710.1186/s12967-024-06060-3Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosisHaohui Lin0Xia Wang1Manhon Chung2Sa Cai3Yu Pan4Laboratory of Regenerative Medicine, The 2nd Affiliated Hospital, Medical School, Shenzhen UniversitySchool of Medicine, The Chinese University of Hong Kong ShenzhenDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineLaboratory of Regenerative Medicine, The 2nd Affiliated Hospital, Medical School, Shenzhen UniversityLaboratory of Regenerative Medicine, The 2nd Affiliated Hospital, Medical School, Shenzhen UniversityAbstract Direct reprogramming has garnered considerable attention due to its capacity to directly convert differentiated cells into desired cells. Fibroblasts are frequently employed in reprogramming studies due to their abundance and accessibility. However, they are also the key drivers in the progression of fibrosis, a pathological condition characterized by excessive extracellular matrix deposition and tissue scarring. Furthermore, the initial stage of reprogramming typically involves deactivating fibrotic pathways. Hence, direct reprogramming offers a valuable method to regenerate target cells for tissue repair while simultaneously reducing fibrotic tendencies. Understanding the link between reprogramming and fibrosis could help develop effective strategies to treat damaged tissue with a potential risk of fibrosis. This review summarizes the advances in direct reprogramming and reveals their anti-fibrosis effects in various organs such as the heart, liver, and skin. Furthermore, we dissect the mechanisms of reprogramming influenced by fibrotic molecules including TGF-β signaling, mechanical signaling, inflammation signaling, epigenetic modifiers, and metabolic regulators. Innovative methods for fibroblast reprogramming like small molecules, CRISPRa, modified mRNA, and the challenges of cellular heterogeneity and senescence faced by in vivo direct reprogramming, are also discussed.https://doi.org/10.1186/s12967-024-06060-3FibrosisFibroblastMyofibroblastDirect reprogrammingIn vivo direct reprogrammingIn situ regeneration |
| spellingShingle | Haohui Lin Xia Wang Manhon Chung Sa Cai Yu Pan Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis Journal of Translational Medicine Fibrosis Fibroblast Myofibroblast Direct reprogramming In vivo direct reprogramming In situ regeneration |
| title | Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis |
| title_full | Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis |
| title_fullStr | Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis |
| title_full_unstemmed | Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis |
| title_short | Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis |
| title_sort | direct fibroblast reprogramming an emerging strategy for treating organic fibrosis |
| topic | Fibrosis Fibroblast Myofibroblast Direct reprogramming In vivo direct reprogramming In situ regeneration |
| url | https://doi.org/10.1186/s12967-024-06060-3 |
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