Disc Regeneration Using MSC Transplanted via the Endplate Route

Abstract

Introduction: Stem cell-based intervertebral disc (IVD)regeneration is quickly moving toward clinical applications.1However, many aspects need to be investigated to routinelytranslate this therapy to clinical applications, in particular, themost efficient way to deliver cell to the IVD. Cells are commonlydelivered to the IVD through the annulus fibrosus (AF) injection.However, recent studies have shown serious drawbacks of thisapproach such as accelerated disc degeneration2,3 and cells leakage.4 As an alternative we have described and tested a new surgical approach to the IVD via the endplate-pedicles (transpedicularapproach). The purpose of the study was to test MSCs/hydrogeltransplantation for IVD regeneration in a grade IV preclinicalmodel of IDD on large size animals5 via the transpedicularapproach6 with cell dose escalation. Methods and Methods:Adult sheep (n = 18) underwent bone marrow aspiration forautologous MSC isolation and expansion. MSC were suspendedin autologous platelet-rich plasma (PRP) and conjugated withhyaluronic acid and batroxobin7 at the time of transplant(MSCs/hydrogel). Nucleotomy was performed via the transpedicular approach in 4 lumbar IVDs and that were injected with (1)hydrogel, (2) low doses ofMSC/hydrogel, (3) high doses ofMSC/hydrogel, and (4) no injection (CTRL). The endplate tunnel wassealed using a polyurethane scaffold. X-ray and MRI (magneticresonance imaging) were performed at baseline and 1, 3, 6, and 12months. Disc macro-and micromorphology were analyzed ateach time point. Results: The MRI index showed a significantdecrease in the untreated group, the disc injected with hydrogeland those injected with low MSC dose compared to healthy discsin all time points. The discs treated with high dose of MSCshowed maintenance of the MRI index compared to the healthydisc. Morphologically, the grade of degeneration evaluated usingthem were in agreement with the grades observed at the MRI.Conclusions:An effective dose of autologousMSC (1 107 cell/mL) delivered via the alternative transpedicular approach regenerates the NP in a preclinical model of grade IV IDD maintainingthe AF intact. This preclinical study has high translational valueas large animal model with the long fallow-up were used, MSCswere expanded in GMP facility simulating the clinical scenario,and the hydrogel were composed of clinically available materials.This approach represent a new valuable strategy to regenerategrade IV degenerated disc of the aging spine.