Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury

Fumiya Kano,Kohki Matsubara,Akihito Yamamoto,Kiyoshi Sakai,Minoru Ueda

doi:10.1016/j.neures.2013.10.010

Abstract

Spinal cord injury (SCI) often leads to persistent functional deficits due to the loss of neurons and glia and to limited axonal regeneration after such injury. Recently, three independent groups have reported marked recovery of hindlimb locomotor function after the transplantation of human adult dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) into rats or mice with acute, sub-acute or chronic SCI. This review summarizes the primary characteristics of human dental pulp stem cells and their therapeutic benefits for treating SCI. Experimental data from multiple preclinical studies suggest that pulp stem cells may promote functional recovery after SCI through multifaceted neuro-regenerative activities.

Highlights

Spinal cord injury (SCI) often leads to persistent functional deficits, due to loss of neurons and glia and to limited axonal regeneration after injury
It has been shown that the array of trophic factors produced by engrafted dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) provide significant therapeutic benefits for the treatment of preclinical animal disease models, including myocardial infarction, systemic lupus erythematosus (SLE), ischemic brain injury, SCI, and colitis (Gandia et al, 2008, Nakashima et al, 2009, Yamaza et al, 2010, de Almeida et al, 2011, Leong et al, 2012, Ma et al, 2012, Sakai et al, 2012, Taghipour et al, 2012, Zhao et al, 2012, Inoue et al, 2013, Yamagata et al, 2013)
Our preliminary analysis showed that these trophic factors, when applied individually, failed to promote the neurite extension of cerebral granular neurons (CGNs) cultured on chondroitin sulfate proteoglycans (CSPG)-coated dishes; it is possible that they may promote axonal regeneration in a synergistic manner

Summary

Introduction

Spinal cord injury (SCI) often leads to persistent functional deficits, due to loss of neurons and glia and to limited axonal regeneration after injury. Three independent groups have reported that transplantation of human adult dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs), into the acute, sub-acute or chronic phase of rat or mouse SCI resulted in marked recovery of hindlimb locomotor functions. This review summarizes the primary characteristics of human dental pulp stem cells and their therapeutic benefits for SCI treatment. Experimental data from a number of preclinical studies suggests that pulp stem cells may promote functional recovery after SCI through multifaceted neuroregenerative activities

Dental pulp stem cells

Brief overview of the pathophysiology of SCI

Anti-inflammatory activity

Regeneration of the injured axon

Anti-apoptotic activity

Cell-replacement activity

Findings

Conclusion