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J Diabetes Investig. 2019 May 29. doi: 10.1111/jdi.13085. [Epub ahead of print]

Secreted factors from cultured dental pulp stem cells promoted neurite outgrowth of dorsal root ganglion neurons and ameliorated neural functions in streptozotocin-induced diabetic mice.

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Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.



Transplantation of stem cells promotes axonal regeneration and angiogenesis in a paracrine manner. In this study, we examined whether the secreted factors in conditioned medium of stem cells from human exfoliated deciduous teeth (SHED-CM) had beneficial effects on diabetic polyneuropathy (DPN) in mice.


SHED-CM was collected 48 hours after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM), and separated into four fractions according to molecular weight. Dorsal root ganglion (DRG) neurons from C57BL/6J mice were cultured with SHED-CM or DMEM to evaluate the effect on neurite outgrowth. Streptozotocin induced diabetic mice were injected with 100 μl of SHED-CM or DMEM into the unilateral hindlimb muscles twice a week over 4 weeks. Peripheral nerve functions were evaluated by the plantar test and motor and sensory nerve conduction velocities (MNCV and SCNV). Intraepidermal nerve fiber densities (IENFDs), capillary number-to-muscle fiber ratio (CNMFR), capillary blood flow and morphometry of sural nerves were also evaluated.


SHED-CM significantly promoted neurite outgrowth of DRG neurons compared with DMEM. Among four fractions of SHED-CM, the only fraction of less than 6 kDa promoted the neurite outgrowth of DRG neurons. In addition, SHED-CM significantly prevented decline in SNCVs compared with DMEM in diabetic mice. Though SHED-CM did not improve IENFDs or morphometry of sural nerves, SHED-CM ameliorated CNMFR and capillary blood flow.


These results suggested that SHED-CM might have a therapeutic effect on DPN through promoting neurite outgrowth and the increase in capillaries might contribute to the improvement of neural function. This article is protected by copyright. All rights reserved.


conditioned medium; diabetic polyneuropathy; stem cells from human exfoliated deciduous teeth

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