High BMPR2 expression leads to enhanced SMAD1/5/8 signalling and GDF6 responsiveness in human adipose-derived stem cells: implications for stem cell therapies for intervertebral disc degeneration. (May 2020)

• Record Type: Journal Article
• Authors: Hodgkinson, Tom; Wignall, Francis; Hoyland, Judith A; Richardson, Stephen M
• Is Part Of: Journal of tissue engineering. Volume 11(2020)
• Publication Date: 2020-05
• Subjects: Intervertebral disc degeneration -- growth differentiation factor 6 -- mesenchymal stem cells -- adipose-derived stem cells -- nucleus pulposus -- bone morphogenetic protein receptor -- SMAD1/5/8 -- ERK1/2; Tissue engineering -- Periodicals; 612.028
• DOI: 10.1177/2041731420919334
• Languages: English
• ISSNs: 2041-7314

Abstract

Stem cell–based regenerative strategies are promising for intervertebral disc degeneration. Stimulation of bone-marrow- and adipose-derived multipotent stem cells with recombinant human growth differentiation factor 6 (rhGDF6) promotes anabolic nucleus pulposus like phenotypes. In comparison to mesenchymal stem cells, adipose-derived multipotent stem cells exhibit greater NP-marker gene expression and proteoglycan-rich matrix production. To understand these response differences, we investigated bone morphogenetic protein receptor profiles in donor-matched human mesenchymal stem cells and adipose-derived multipotent stem cells, determined differences in rhGDF6 signalling and their importance in NP-like differentiation between cell populations. Bone morphogenetic protein receptor expression in mesenchymal stem cells and adipose-derived multipotent stem cells revealed elevated and less variable expression of BMPR2 in adipose-derived multipotent stem cells, which corresponded with increased downstream pathway activation (SMAD1/5/8, ERK1/2). Inhibitor studies demonstrated SMAD1/5/8 signalling was required for rhGDF6-induced nucleus-pulposus-like adipose-derived multipotent stem cell differentiation, while ERK1/2 contributed significantly to critical nucleus pulposus gene expression, aggrecan and type II collagen production. These data inform cell regenerative therapeutic choices for intervertebral disc degeneration regeneration and identify further potential optimisation targets.