Abstract
BackgroundDental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. In our previous study, we demonstrated that cryopreserved rat DPSCs improved diabetic polyneuropathy and that the efficacy of cryopreserved rat DPSCs was equivalent to that of freshly isolated rat DPSCs. The present study was conducted to evaluate whether transplantation of cryopreserved human DPSCs (hDPSCs) is also effective for the treatment of diabetic polyneuropathy.MethodshDPSCs were isolated from human impacted third molars being extracted for orthodontic reasons. Eight weeks after the induction of diabetes in nude mice, hDPSCs (1 × 105/limb) were unilaterally transplanted into the hindlimb skeletal muscle, and vehicle (saline) was injected into the opposite side as a control. The effects of hDPSCs were analyzed at 4 weeks after transplantation.ResultshDPSC transplantation significantly ameliorated reduced sensory perception thresholds, delayed nerve conduction velocity, and decreased the blood flow to the sciatic nerve in diabetic mice 4 weeks post-transplantation. Cultured hDPSCs secreted the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) proteins. A subset of the transplanted hDPSCs was localized around the muscle bundles and expressed the human VEGF and NGF genes at the transplanted site. The capillary/muscle bundle ratio was significantly increased on the hDPSC-transplanted side of the gastrocnemius muscles in diabetic mice. Neutralizing antibodies against VEGF and NGF negated the effects of hDPSC transplantation on the nerve conduction velocity in diabetic mice, suggesting that VEGF and NGF may play roles in the effects of hDPSC transplantation on diabetic polyneuropathy.ConclusionsThese results suggest that stem cell transplantation with hDPSCs may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors.
Highlights
Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation
Hata et al Stem Cell Research & Therapy (2020) 11:236 (Continued from previous page). These results suggest that stem cell transplantation with Human dental pulp stem cell (hDPSC) may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors
motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and Sciatic nerve blood flow (SNBF) improvements induced by hDPSC transplantation We evaluated the MNCV and SNCV at 4 weeks after hDPSC transplantation (Fig. 2d), revealing significantly reduced values on the vehicle-injected side of the diabetic mice compared with the normal mice
Summary
Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. Dental pulp stem cells (DPSCs) in the dental pulp cavity have high self-renewal and proliferation activity and multipotency in terms of differentiation, similar to bone marrow-derived MSCs [1]. The pathogenesis of diabetic polyneuropathy is mainly neuronal and vascular disorders [8]. Vascular abnormalities have been observed in diabetic polyneuropathy, which suggests the existence of ischemic damage [12, 13]. The current therapies for diabetic polyneuropathy mainly aim to manage the symptom of pain in addition to improving glycemic control [6]. Curative therapies are needed based on the pathogenesis of diabetic polyneuropathy
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