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

培养牙髓干细胞分泌的因子促进了背根神经节神经元的神经突生长,并改善了链脲佐菌素诱发的糖尿病小鼠的神经功能

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作者:Emiri Miura-Yura, Shin Tsunekawa, Keiko Naruse, Nobuhisa Nakamura, Mikio Motegi, Hiromi Nakai-Shimoda, Saeko Asano, Makoto Kato, Yuichiro Yamada, Takako Izumoto-Akita, Akihito Yamamoto, Tatsuhito Himeno, Masaki Kondo, Yoshiro Kato, Jiro Nakamura, Hideki Kamiya

Conclusions

These results suggested that SHED-CM might have a therapeutic effect on diabetic polyneuropathy through promoting neurite outgrowth, and the increase in capillaries might contribute to the improvement of neural function.

Methods

Conditioned medium of stem cells from human exfoliated deciduous teeth was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM), and separated into four fractions according to molecular weight. Dorsal root ganglion 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 a period of 4 weeks. Peripheral nerve functions were evaluated by the plantar test, and motor and sensory nerve conduction velocities. Intraepidermal nerve fiber densities, capillary number-to-muscle fiber ratio, capillary blood flow and morphometry of sural nerves were also evaluated.

Results

Conditioned medium of stem cells from human exfoliated deciduous teeth significantly promoted neurite outgrowth of dorsal root ganglion neurons compared with DMEM. Among four fractions of SHED-CM, the only fraction of <6 kDa promoted the neurite outgrowth of dorsal root ganglion neurons. In addition, SHED-CM significantly prevented decline in sensory nerve conduction velocities compared with DMEM in diabetic mice. Although SHED-CM did not improve intraepidermal nerve fiber densities or morphometry of sural nerves, SHED-CM ameliorated the capillary number-to-muscle fiber ratio and capillary blood flow. Conclusions: These results suggested that SHED-CM might have a therapeutic effect on diabetic polyneuropathy through promoting neurite outgrowth, and the increase in capillaries might contribute to the improvement of neural function.

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