title: 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.
authors: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kiyoshi
authors: K
authors: Sakai
authors: Akihito
authors: A
authors: Yamamoto
authors: Kohki
authors: K
authors: Matsubara
authors: Shoko
authors: S
authors: Nakamura
authors: Mami
authors: M
authors: Naruse
authors: Mari
authors: M
authors: Yamagata
authors: Kazuma
authors: K
authors: Sakamoto
authors: Ryoji
authors: R
authors: Tauchi
authors: Norimitsu
authors: N
authors: Wakao
authors: Shiro
authors: S
authors: Imagama
authors: Hideharu
authors: H
authors: Hibi
authors: Kenji
authors: K
authors: Kadomatsu
authors: Naoki
authors: N
authors: Ishiguro
authors: Minoru
authors: M
authors: Ueda
mesh_terms: D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000473:pathology; D002454:Cell Differentiation; D002470:Cell Survival; D017077:Culture Media, Conditioned; D003782:Dental Pulp / Q000166:cytology*; D005260:Female; D005347:Fibroblasts / Q000637:transplantation; D006614:Hindlimb; D006801:Humans; D008124:Locomotion / Q000502:physiology; D009186:Myelin Sheath / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology; D019899:Paracrine Communication; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017154:Stromal Cells / Q000637:transplantation; D014183:Transplantation, Heterologous; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors
chemical_list: D017077:Culture Media, Conditioned; D020741:rho GTP-Binding Proteins