BMP-3 Promotes Matrix Production in Co-cultured Stem Cells and Disc Cells from Low Back Pain Patients.

Low back pain is one of the most common disorders and believed to be due to intervertebral disc degeneration. Transplantation of human mesenchymal stem cells (hMSCs) is suggested as potential treatment option. Bone morphogenetic growth factor 3 (BMP-3) promotes chondrogenesis and is proven effective in enhancing chondrogenesis in hMSCs pretreated with interleukin-1 beta (IL-1β) in hydrogel model. Three-dimensional co-cultures of hMSCs and disc cells (DCs) have previously been demonstrated to result in increased proteoglycan production. The aim was to study the effects of BMP-3 on hMSCs, DCs, as well as hMSCs and DCs in co-culture in a pellet system, both as single treatment and after pretreatment of IL-1β. Cell pellet cultures with hMSCs, DCs, and co-culture (1:1 ratio) were performed and stimulated with BMP-3 at 1 or 10 ng/mL concentrations. For pretreatment (PRE-T), cell pellets were first stimulated with IL-1β, for 24 h, and then BMP-3. The pellets were harvested on day 7, 14, and 28. Results demonstrated that BMP-3 stimulation at 10 ng/mL promoted cell viability, proteoglycan accumulation, as well as chondrogenesis in all pellet groups compared to 1 ng/mL. Cellular proliferation and chondrogenic differentiation of hMSCs were best promoted by PRE-T at 10 ng/mL, whereas BMP-3 best enhanced chondrogenesis in DC and co-culture pellets at the same concentration. Impact Statement Current therapies for low back pain include pain modulation and surgery, which do not tackle the underlying cellular mechanisms of the degenerated intervertebral discs (IVDs). To develop an understanding of the degeneration process and to further reverse its course, the effects of growth factor and cytokine on the native cells of the IVDs were investigated, revealing the potency of bone morphogenetic growth factor 3 on disc cells (DCs) and combined culture of mesenchymal stem cells and DCs. These results may impact future strategies in development of cell therapies that could directly influence the IVD degeneration process, which might alter the treatment models of today.