Abstract
Background
Stem cell based intervertebral disc (IVD) regeneration is quickly moving towards clinical applications. However, many aspects need to be investigated to routinely translate this therapy to clinical applications, in particular, the most efficient way to deliver cell to the IVD. Cells are commonly delivered to the IVD through the annulus fibrosus (AF) injection. However, recent studies have shown serious drawbacks of this approach. As an alternative we have described and tested a new surgical approach to the IVD via the endplate-pedicles (transpedicular approach). The Purpose of the study was to test MSCs/hydrogel transplantation for IVD regeneration in a grade IV preclinical model of IDD on large size animals via the transpeducular approach with cell dose escalation.
Methods
Adult sheep (n=18) underwent bone marrow aspiration for autologous MSC isolation and expansion. MSC were suspended in autologous PRP and conjugated with Hyaluronic Acid and Batroxobin at the time of transplant (MSCs/hydrogel). Nucleotomy was performed via the transpedicular approach in four lumbar IVDs and that were injected with 1) hydrogel, 2) Low doses of MSC/hydrogel, 3) High doses of MSC/hydrogel, 4) no injection (CTRL). The endplate tunnel was sealed using a polyurethane scaffold. X-ray and MRI were performed at baseline and 1,3,6,12 months. Disc macro- and micro-morphology were analysed at each time point.
Results
The MRI index showed a significant decrease in the untreated group, the disc injected with hydrogel and those injected with low MSC dose compared to healthy discs in all time points. The discs treated with high dose of MSC showed maintenance of the MRI index compared to the healthy disc. Morphologically, the grade of degeneration evaluated using the were in agreement with the grades observed at the MRI.
Conclusions
An effective dose of autologous MSC (1−107 cell/ml) delivered via the alternative transpedicular approach regenerates the NP in a preclinical model of grade IV IDD maintaining the AF intact This preclinical study has high translational value as large animal model with the long fallow up were used, MSCs were expanded in GMP facility simulating the clinical scenario, and the hydrogel were composed of clinically available drags and materials.
