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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Main Authors: Haohui Lin, Xia Wang, Manhon Chung, Sa Cai, Yu Pan
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Translational Medicine
Subjects:
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.
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institution OA Journals
issn 1479-5876
language English
publishDate 2025-02-01
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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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AT manhonchung directfibroblastreprogramminganemergingstrategyfortreatingorganicfibrosis
AT sacai directfibroblastreprogramminganemergingstrategyfortreatingorganicfibrosis
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