Bone marrow stromal cells in Modic type 1 changes promote neurite outgrowth

Tamara Mengis; Nick Herger; Irina Heggli; Jan Devan; José Miguel Spirig; Christoph J Laux; Florian Brunner; Mazda Farshad; Oliver Distler; Stefan Dudli

doi:10.3389/fcell.2023.1286280

Bone marrow stromal cells in Modic type 1 changes promote neurite outgrowth

Front Cell Dev Biol. 2023 Oct 25:11:1286280. doi: 10.3389/fcell.2023.1286280. eCollection 2023.

Authors

Tamara Mengis^{1

2}, Nick Herger^{1

2}, Irina Heggli^{1

2}, Jan Devan^{1

2}, José Miguel Spirig³, Christoph J Laux³, Florian Brunner², Mazda Farshad³, Oliver Distler¹, Stefan Dudli^{1

2}

Affiliations

¹ Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zürich, Switzerland.
² Department of Physical Medicine and Rheumatology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland.
³ Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zürich, Switzerland.

Abstract

The pain in patients with Modic type 1 changes (MC1) is often due to vertebral body endplate pain, which is linked to abnormal neurite outgrowth in the vertebral body and adjacent endplate. The aim of this study was to understand the role of MC1 bone marrow stromal cells (BMSCs) in neurite outgrowth. BMSCs can produce neurotrophic factors, which have been shown to be pro-fibrotic in MC1, and expand in the perivascular space where sensory vertebral nerves are located. The study involved the exploration of the BMSC transcriptome in MC1, co-culture of MC1 BMSCs with the neuroblastoma cell line SH-SY5Y, analysis of supernatant cytokines, and analysis of gene expression changes in co-cultured SH-SY5Y. Transcriptomic analysis revealed upregulated brain-derived neurotrophic factor (BDNF) signaling-related pathways. Co-cultures of MC1 BMSCs with SH-SY5Y cells resulted in increased neurite sprouting compared to co-cultures with control BMSCs. The concentration of BDNF and other cytokines supporting neuron growth was increased in MC1 vs. control BMSC co-culture supernatants. Taken together, these findings show that MC1 BMSCs provide strong pro-neurotrophic cues to nearby neurons and could be a relevant disease-modifying treatment target.

Keywords: Modic changes; basivertebral nerve; low back pain; neurite outgrowth; neurotrophic; stromal cells.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by a career research grant from the Foundation for Research in Rheumatology (FOREUM) (SD and OD), by a grant from the Center of Applied Biotechnology and Molecular Medicine of the University of Zurich (SD), and by a grant from the Swiss National Fond (SD, Grant No. 207989).