Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells for Treating Complete Spinal Cord Injury

Background: Spinal cord injury (SCI) involves loss of motor, sensory, and/or autonomic function. Important barriers to recovery include lack of neurotrophic support and vascular supply to the spinal cord lesion. Human dental pulp stem cells (DPSCs) are easily accessible stem cells with paracrine-mediated neuroregenerative and angiogenic potentials.

Methods: To examine DPSCs’ neurotrophic and angiogenic effects, DPSCs were co-cultured with PC12 cells or endothelial cells (ECs) on 3D porous PLLA/PLGA scaffolds, respectively. Scaffolds bearing highly developed vessels supported by DPSCs after one-week cultivation were implanted to rats with complete SCI transection. Thereafter, motor and sensory behavioral assessments and were performed, followed by neuroanatomical sensory tract tracing, histology analysis, and micro-CT scanning and quantification of 3D vasculature in the remodelled spinal cord lesions.

Results: DPSCs secreted neurotrophic factors, which induced the differentiation of PC12 cells to neuron-like cells on 3D scaffolds. Additionally, more rapid, stable, and mature vascular networks were formed when ECs were supported by DPSCs, as compared to other supporting cells. Transplantation of prevascularized DPSC-embedded scaffolds to rats with complete SCI led to significant sensory recovery within eight weeks. Histological analysis showed robust axonal regeneration, myelin formation, and angiogenesis. 3D micro-CT analysis of spinal cord lesions clearly demonstrated more significant neovascularization especially in the sensory regions, upon the implantation of prevascularized DPSC-embedded scaffolds as compared to the transection controls.

Conclusion: Taken together, prevascularized constructs bearing DPSCs enhance functional recovery via potent neurotrophic and angiogenic effects, and constitute a promising treatment for SCI individuals.