Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning

Author:

Frommer Marvin L.123,Langridge Benjamin J.123ORCID,Beedie Alexandra13,Jasionowska Sara13,Awad Laura13,Denton Christopher P.4,Abraham David J.4,Abu-Hanna Jeries15,Butler Peter E. M.123

Affiliation:

1. Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK

2. Department of Surgical Biotechnology, Division of Surgery & Interventional Science, University College London, London NW3 2QG, UK

3. Department of Plastic Surgery, Royal Free Hospital, London NW3 2QG, UK

4. Centre for Rheumatology, Department of Inflammation and Rare Diseases, Division of Medicine, University College London, London NW3 2QG, UK

5. Division of Medical Sciences, University of Oxford, Oxford OX3 9DU, UK

Abstract

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-β, TGF-β1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-β induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-β1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

Publisher

MDPI AG

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