Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc injury model

Abstract

Study Design: In vivo randomized controlled study in the goat intervertebral disc (IVD) injury model.

Objective: To define the effects of allogeneic bone marrow-derived stromal cell injected into the degenerating goat IVDs.

Summary of Background Data: Transplantation of bone marrow stromal cells to the degenerating disc has been suggested as a means to correct the biologic incompetence of the disc. However, large animal models with IVDs similar in shape and size to those of humans are needed to define the efficacy and safety of this approach.

Methods: Goat IVD degeneration was induced by stabbing with a #15 blade. One month after disc injury, the injured discs were randomly selected to receive goat bone marrow-derived stromal cell (suspended in hydrogel), saline (control), or hydrogel (control) injections. Three and 6 months after stem cell transplantation, goats were euthanized and the IVD were examined for biochemical content and tissue morphology. MR images at 3- and 6-month time points were also examined.

Results: The goat large animal model shows early degenerative changes following disc injury. Degenerating IVDs injected with bone marrow stromal cells showed significantly increased proteoglycan (PG) accumulation within their nucleus pulposus (NP) region. However, collagen content, MRI grade and histology did not show statistically significant differences between the cell-treated and control IVDs.

Conclusions: Following transplantation of bone marrow stromal cells, NP tissue contained more PG than control discs. Although this result was promising, the rate and severity of degeneration in this goat disc injury were modest, suggesting that a more severe injury and a larger sample size is indicated for future studies to better define the utility of cell therapies in this model.

Figures

Figure 1. Instruments used and sample X-rays obtained during surgery

A. # 15 blade used to create disc injuries; B & C: lateral X-ray of the goat spine documenting position of the instruments; B. 14 mm tubular retractor docked at the lateral margin of the intervertebral disc (IVD); C. #15 blade inserted into the IVD.

Figure 2. Proteoglycan (PG) content in goat nucleus pulposus (NP) tissues three and six months after transplantation of bone marrow stromal cells, normalized to DNA content

Error bar stands for standard error of the mean; * indicates statistical significance (p≤0.05).

Figure 3. MRI grades of uninjured control discs

Panel A on the left shows MRI grades according to Pfirman et al. Panel B on the right is a representative T2-weighted MR image of a goat spine. Error bar stands for standard error of the mean, * indicates statistical significance (p≤0.05) compared to L2/3. Note that a higher score indicates more severe degeneration.