INTRODUCTION: Biologic treatment options for intervertebral discs(IVDs) have been suggested for patients with chronic low back pain. The aim with this study was to investigate possible cell types and gel carriers for regenerative treatment of degenerative discs.
METHODS: In vitro; human mesenchymal cells(hMSC), human IVD cells(hDC) and human chondrocytes(hC) were cultivated respectively in three different gel types; hyaluronan based gel(Durolane®), hydrogel(Puramatrix® and adhesive tissue glue gel (TISSEEL®). The cells were cultivated 9 days in chondrogenic‐differentiation media.Cell proliferation and proteoglycan production was evaluated with microscopy, Nikon Eclipse90i.
In vivo; Lumbar IVDs were injured in 6 mini pigs. After 2 weeks, hMSCs or hC were injected into the IVDs with the hyaluronan gel. Animals were sacrificed after 3 or 6 months. Transplanted hMSC were traced with an anti human antibody. IVD appearance: visualized by MRI and immunohistochemistry.
RESULTS: Cell proliferation was most advanced in the hyaluronan gel in the in vitro cultures, all cell types. Xenotransplanted hMSC and hC survived in the porcine IVDs for 6 months and produced Collagenll in 6/6 animals. Six months after transplantation of cell/gel, pronounced endplate changes indicating severe IVD degeneration was seen in 1/3 hC/gel, 1/3 hMSC and 1/3 gel only injected IVDs at MRI. At time point 6 months after transplantation: 1/3 hMSC/gel, 3/3 hC/gel, 2/3 gel and 1/3 injured IVDs stained positive for bone mineralization.
DISCUSSION: Even though hyaluronan gel demonstrated best result of the tested gels in vitro it was not a suitable cell carrier for cell therapy. High cell proliferation observed in vitro may have been a negative factor in vivo, since most of the cell/gel transplanted IVDs showed degenerative changes at MRI and induced bone formation. However, xenotransplantation is a valuable model for evaluating possibilities for cell therapy treatment of human degenerated IVDs.