Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms

TLDR

Spinal cord injury causes lasting functional deficits by losing neurons and glia and limiting axonal regeneration. Human dental pulp stem cells mitigate SCI by inhibiting apoptosis of neurons, astrocytes, and oligodendrocytes; promoting axon regeneration through paracrine inhibition of growth inhibitors; and replacing lost cells by differentiating into mature oligodendrocytes. Transplantation of human dental pulp stem cells into a completely transected adult rat spinal cord markedly improved hind limb locomotor recovery, outperforming bone marrow stromal cells or skin-derived fibroblasts, and demonstrating neuroregenerative benefits via cell‑autonomous and paracrine mechanisms.

Abstract

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.