Abstract
Current therapies for intervertebral disc degeneration are aimed at treating the pathologic and disabling conditions arising from discopathy rather than directly treating the underlying problem of disc degeneration. Our group is exploring the potential of cell therapy to repopulate the disc and stop the progressive loss of proteoglycans. Stem cells appear to be excellent candidates for this purpose, based on their ability to differentiate along multiple connective tissue lineages. The purpose of this study is to investigate the interaction between stem cells and nucleus polposus cells to test the feasibility of stem cell therapy for the treatment of disc degeneration.
Human nucleus polposus cells (NPCs) were isolated from patients undergoing disc surgery and were co-cultured for 2 weeks with muscle-derived stem cells (MdSCs) from 3-week-old mdx mice in monolayer culture system at different ratio with or without added TGF-β1. Each well contained an admixture of cells with NPC-to-SC ratios of 0:100, 25:75, 50:50, 75:25, and 100:0. Proteoglycan synthesis and DNA content were measured.
Co-culturing of NPCs with MdSCs in the monolayer culture system resulted in vigorous increases in proteoglycans synthesis as compared with NPCs alone and MdSCs alone both with and without TGF-β1. The increases were on the 200% for an NPC-to-MDSC ratio of 75:25. Addition of TGF-β1 to the NPC and MDSC co-cultures resulted in further increases up to 400%. DNA content also increased with co-culture.
The data from this study show that there is a synergistic effect between stem cells and nNPC resulting in upregulated proteoglycan synthesis in vitro. The observed benefits of co-culture might be due either to stem cell plasticity, the stem cells trans-differentiation towards chondrocyte-like cells, or the stimulation of NPC by agents synthesised by stem cells or other mechanisms. Elucidation of the precise mechanisms of action may permit development of strategies to optimise the synergistic effects in vivo. These results support the feasibility of developing a stem cell therapy approach to treat and prevent intervertebral disc degeneration.
