eCM (Eur Cell Mater / e Cells & Materials) eCM Open Access Scientific Journal
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2022   Volume No 44 – pages 101-114

Title: FGF2 overrides key pro-fibrotic features of bone marrow stromal cells isolated from Modic type 1 change patients

Authors: I Heggli, U Blache, N Herger, T Mengis, PK Jaeger, R Schuepbach, N Farshad-Amacker, F Brunner, JG Snedeker, M Farshad, O Distler, S Dudli

Address: Balgrist Campus AG, Lengghalde 5, 8008 Zurich, Switzerland

E-mail: irina.heggli at usz.ch

Abstract: Extensive extracellular matrix production and increased cell-matrix adhesion by bone marrow stromal cells (BMSCs) are hallmarks of fibrotic alterations in the vertebral bone marrow known as Modic type 1 changes (MC1). MC1 are associated with non-specific chronic low-back pain. To identify treatment targets for MC1, in vitro studies using patient BMSCs are important to reveal pathological mechanisms. For the culture of BMSCs, fibroblast growth factor 2 (FGF2) is widely used. However, FGF2 has been shown to suppress matrix synthesis in various stromal cell populations. The aim of the present study was to investigate whether FGF2 affected the in vitro study of the fibrotic pathomechanisms of MC1-derived BMSCs. Transcriptomic changes and changes in cell-matrix adhesion of MC1-derived BMSCs were compared to intra-patient control BMSCs in response to FGF2. RNA sequencing and quantitative real-time polymerase chain reaction revealed that pro-fibrotic genes and pathways were not detectable in MC1-derived BMSCs when cultured in the presence of FGF2. In addition, significantly increased cell-matrix adhesion of MC1-derived BMSCs was abolished in the presence of FGF2. In conclusion, the data demonstrated that FGF2 overrides key pro-fibrotic features of MC1 BMSCs in vitro. Usage of FGF2-supplemented media in studies of fibrotic mechanisms should be critically evaluated as it could override normally dominant biological and biophysical cues.

Keywords: Bone marrow stromal cells, fibroblast growth factor 2, basic fibroblast growth factor, Modic changes, fibrosis, extracellular matrix, cell-matrix adhesion.

Publication date: October 3rd 2022

Article download: Pages 101-114 (PDF file)
DOI:
10.22203/eCM.v044a07

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