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

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

“…SHEDs exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. We showed previously that SHED transplantation into completely transected rat spinal cord resulted in the functional recovery of hind limb locomotion (14). Moreover, SHED engraftment promotes functional recovery from various acute and chronic CNS insults through paracrine mechanisms that activate endogenous tissue-repairing activity (15,16).…”

“…They are thought to originate from the cranial neural crest and express early mesenchymal and neuroectodermal stem cell markers (11). In addition, they can differentiate into functional neurons and oligodendrocytes under the appropriate conditions (12)(13)(14). SHEDs exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases.…”

Chimeric Allografts Induced by Short‐Term Treatment With Stem Cell Mobilizing Agents Result in Long‐Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine

“…Recent reports have described the therapeutic benefit of providing exogenous allogeneic stem cells for a heterogeneous group of clinical injuries (1)(2)(3). Endogenous autologous stem cells have also been shown to participate in injury repair and regeneration in many experimental (4)(5)(6) and clinical scenarios (7)(8)(9)(10), and some have compared the two sources of stem cells for relative clinical efficacy (11).…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…Human SHEDs transplanted into completely transected adult rat spinal cord resulting in the functional recovery of hind limb locomotion (Sakai et al 2012). SHED engraftment promotes also functional recovery from several acute and chronic CNS injuries through paracrine mechanisms triggering endogenous tissue-repairing action (Inoue et al 2013;Yamagata et al 2013).…”