Transplantation of dental pulp stem cells improves long-term diabetic polyneuropathy together with improvement of nerve morphometrical evaluation

Abstract

BackgroundAlthough previous reports have revealed the therapeutic potential of stem cell transplantation in diabetic polyneuropathy, the effects of cell transplantation on long-term diabetic polyneuropathy have not been investigated. In this study, we investigated whether the transplantation of dental pulp stem cells (DPSCs) ameliorated long-term diabetic polyneuropathy in streptozotocin (STZ)-induced diabetic rats.MethodsForty-eight weeks after STZ injection, we transplanted DPSCs into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation (i.e., 52 weeks after STZ injection) the effects of DPSC transplantation on diabetic polyneuropathy were assessed.ResultsSTZ-induced diabetic rats showed significant reductions in the sciatic motor/sensory nerve conduction velocity, increases in the current perception threshold, and decreases in capillary density in skeletal muscles and intra-epidermal nerve fiber density compared with normal rats, all of which were ameliorated by DPSC transplantation. Furthermore, sural nerve morphometrical analysis revealed that the transplantation of DPSCs significantly increased the myelin thickness and area. DPSC-conditioned media promoted the neurite outgrowth of dorsal root ganglion neurons and increased the viability and myelin-related protein expression of Schwann cells.ConclusionsThese results indicated that the transplantation of DPSCs contributed to the neurophysiological and neuropathological recovery from a long duration of diabetic polyneuropathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0729-5) contains supplementary material, which is available to authorized users.

Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti‐inflammatory, neuroprotective and angiogenic actions: Cell‐free regenerative medicine for diabetic polyneuropathy

“…We have previously reported the therapeutic effect of DPSC transplantation on diabetic polyneuropathy. However, many of the engrafted DPSCs disappeared from the transplanted site during a certain period after transplantation, which is consistent with other cell transplantation therapies for ischemic heart disease and brain infarction.…”

“…Under inflammatory conditions, DPSC‐CM increased the anti‐inflammatory marker genes, CD206 and interleukin‐10, in macrophages and induced M2 polarization. In neuronal cells, DPSC‐CM elongated neurite outgrowth of dorsal root ganglion cells, and increased the proliferation and myelin formation of Schwann cells.…”

“…We showed that DPSC‐CM improved the decrease in capillary density in the skeletal muscles of diabetic rats. This phenomenon might be due to the direct angiogenic effects of DPSC‐CM, as DPSC‐CM contains abundant VEGF and significantly increases the viability of HUVECs in culture. However, the direct relationship between capillary density in the skeletal muscles and diabetic neuropathy is still unclear.…”

Direct Comparison of Therapeutic Effects on Diabetic Polyneuropathy between Transplantation of Dental Pulp Stem Cells and Administration of Dental Pulp Stem Cell-Secreted Factors

“…Previously studied regenerative medicine for diabetic polyneuropathy mainly included stem cell transplantation therapies. The therapeutic mechanisms of stem cell transplantation on diabetic polyneuropathy are the following: (1) angiogenesis and improvement of blood flow, (2) anti-inflammatory action, and (3) neuroprotective action [ 7 , 11 , 13 , 14 , 23 , 24 ]. On the other hand, in related studies, most grafted progenitor/stem cells consistently disappeared sometime after transplantation [ 11 , 18 , 25 ].…”

“…Since orthodontic extractions are performed at a young age in many cases, we can easily obtain young DPSCs, which may overcome stem cell dysfunction due to aging or diseases. Using streptozotocin (STZ)-induced diabetic models, we confirmed that the transplantation of DPSCs ameliorated diabetic polyneuropathy [ 11 , 13 , 14 ].…”