Evaluation of intervertebral disc regeneration with injection of mesenchymal stem cells encapsulated in PEGDA-microcryogel delivery system using quantitative T2 mapping: a study in canines

摘要

Intervertebral disc degeneration (IDD), the primary cause of low back pain, is still a great challenge to spinal surgeons and clinicians. T2 mapping, a biochemical magnetic resonance imaging (MRI) technique to calculate relaxation time, has the potential to offer a quantitative assessment of IDD. The aim of the study was to evaluate the regenerative effects of adipose-derived mesenchymal stem cells (MSCs) encapsulated in PEGDA-microcryogels (PMs) reinforced alginate hydrogel (AH) on the degenerative intervertebral disc (IVD) in a canine model using T2 mapping. Four degeneration-induced IVDs (L3-L4 to L6-L7) of 12 adult beagle dogs were injected with phosphate-buffered saline (PBS), MSCs, AH-PMs, and MSCs-laden AH-PMs, respectively. The intact IVD L7-S1 served as the normal control. IVD height change on plain radiograph, Pfirrmann grade and T2 relaxation time on MRI, histological change, and extracellular matrix (ECM)-associated proteins were evaluated during the 24-week follow-up period. Injection of MSCs-laden AH-PMs had the most satisfactory effects, having less decrease of IVD height, lower Pfirrmann grade, milder histological change, and longer T2 relaxation time (P < 0.05). T2 relaxation time was positively correlated with ECM content (proteoglycan: r = 0.85, P < 0.001; collagen II: r = 0.79, P < 0.001) and IVD height (r = 0.81, P < 0.001), but negatively correlated with Pfirrmann grade and histological grade (rho = -0.86, P < 0.001; rho = -0.95, P < 0.001). These results suggest that T2 mapping has the potential to quantitatively evaluate the repairing effects of cell-based engineering treatments on IDD for a long-term follow-up.