Disc cell therapy with bone-marrow-derived autologous mesenchymal stromal cells in a large porcine disc degeneration model.

Abstract

Disc regeneration through matrix-assisted autologous mesenchymal stromal cell therapy seems promising against disc degeneration with convincing results in small animal models. Whether these positive results can be transferred to larger animal models or humans is unclear. Fibrin matrix-assisted autologous bone-marrow-derived mesenchymal stromal cell therapy was compared to acellular fibrin matrix therapy in a porcine in vivo model. First, disc degeneration was induced by annular puncture and partial nucleotomy with a large 16G-needle, and 12weeks later, disc therapy was performed in a second surgery with a thinner 26G needle. Seventy-two lumbar discs from 12 aged adult pigs were evaluated by histology, micro-CT, and gene expression analysis 13 and 24 weeks after nucleotomy and 1 and 12 weeks after treatment, respectively. Radiologic disc height was not significantly different in both treatment groups. In the semi-quantitative histologic degeneration score, significant disc degeneration was still evident 1week after treatment both in the mesenchymal stromal cell group and in the acellular fibrin matrix group. 12 weeks after treatment, degeneration was, however, not further increased and mesenchymal-stromal-cell-treated discs showed significantly less disc degeneration in the annulus fibrosus (p = 0.02), whereas reduction in the nucleus pulposus did not reach statistical significance. Cell treatment compared to matrix alone found less Col1 gene expression as a marker for fibrosis and more expression of the trophic factor BMP2 in the nucleus pulposus, whereas the inflammation marker IL1ß was reduced in the annulus fibrosus. Disc treatment with fibrin matrix-assisted autologous mesenchymal stromal cells reduced degenerative findings compared to acellular fibrin matrix alone. Regenerative changes, however, were not significant for all parameters showing limitations in a large biomechanically demanding model with aged discs. These slides can be retrieved under Electronic Supplementary Material.