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

Cells. 2024 Apr 17;13(8):693. doi: 10.3390/cells13080693.

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.

Keywords: RNA sequencing; adipose-derived stem cells; fetal bovine serum; fibrosis; hypoxia; interleukin 1 beta; skin fibrosis; transforming growth factor beta 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue* / cytology
  • Adipose Tissue* / metabolism
  • Animals
  • Cell Hypoxia / genetics
  • Fibrosis*
  • Gene Expression Profiling*
  • Humans
  • Inflammation* / genetics
  • Inflammation* / pathology
  • Stem Cells* / metabolism
  • Transcriptome / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Transforming Growth Factor beta1

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.