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Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy

AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSCs increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory e...

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Autores principales: Omi, Maiko, Hata, Masaki, Nakamura, Nobuhisa, Miyabe, Megumi, Kobayashi, Yasuko, Kamiya, Hideki, Nakamura, Jiro, Ozawa, Shogo, Tanaka, Yoshinobu, Takebe, Jun, Matsubara, Tatsuaki, Naruse, Keiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931198/
https://www.ncbi.nlm.nih.gov/pubmed/27181261
http://dx.doi.org/10.1111/jdi.12452
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author Omi, Maiko
Hata, Masaki
Nakamura, Nobuhisa
Miyabe, Megumi
Kobayashi, Yasuko
Kamiya, Hideki
Nakamura, Jiro
Ozawa, Shogo
Tanaka, Yoshinobu
Takebe, Jun
Matsubara, Tatsuaki
Naruse, Keiko
author_facet Omi, Maiko
Hata, Masaki
Nakamura, Nobuhisa
Miyabe, Megumi
Kobayashi, Yasuko
Kamiya, Hideki
Nakamura, Jiro
Ozawa, Shogo
Tanaka, Yoshinobu
Takebe, Jun
Matsubara, Tatsuaki
Naruse, Keiko
author_sort Omi, Maiko
collection PubMed
description AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSCs increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory effects of DPSC transplantation on diabetic peripheral nerves. MATERIALS AND METHODS: DPSCs were isolated from the dental pulp of Sprague–Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection, DPSCs were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation, neurophysiological measurements, inflammatory gene expressions and the number of CD68‐positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of DPSCs, the effects of DPSC‐conditioned media on lipopolysaccharide‐stimulated murine macrophage RAW264.7 cells were investigated. RESULTS: Diabetic rats showed significant delays in sciatic nerve conduction velocities and decreased sciatic nerve blood flow, all of which were ameliorated by DPSC transplantation. The number of CD68‐positive monocytes/macrophages and the gene expressions of M1 macrophage‐expressed cytokines, tumor necrosis factor‐α and interleukin‐1β, were increased in the sciatic nerves of the diabetic rats. DPSC transplantation significantly decreased monocytes/macrophages and tumor necrosis factor‐α messenger ribonucleic acid expression, and increased the gene expression of the M2 macrophage marker, CD206, in the sciatic nerves of the diabetic rats. The in vitro study showed that DPSC‐conditioned media significantly increased the gene expressions of interleukin‐10 and CD206 in lipopolysaccharide‐stimulated RAW264.7 cells. CONCLUSIONS: These results suggest that DPSC transplantation promoted macrophages polarization towards anti‐inflammatory M2 phenotypes, which might be one of the therapeutic mechanisms for diabetic polyneuropathy.
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spelling pubmed-49311982016-07-06 Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy Omi, Maiko Hata, Masaki Nakamura, Nobuhisa Miyabe, Megumi Kobayashi, Yasuko Kamiya, Hideki Nakamura, Jiro Ozawa, Shogo Tanaka, Yoshinobu Takebe, Jun Matsubara, Tatsuaki Naruse, Keiko J Diabetes Investig Articles AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSCs increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory effects of DPSC transplantation on diabetic peripheral nerves. MATERIALS AND METHODS: DPSCs were isolated from the dental pulp of Sprague–Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection, DPSCs were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation, neurophysiological measurements, inflammatory gene expressions and the number of CD68‐positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of DPSCs, the effects of DPSC‐conditioned media on lipopolysaccharide‐stimulated murine macrophage RAW264.7 cells were investigated. RESULTS: Diabetic rats showed significant delays in sciatic nerve conduction velocities and decreased sciatic nerve blood flow, all of which were ameliorated by DPSC transplantation. The number of CD68‐positive monocytes/macrophages and the gene expressions of M1 macrophage‐expressed cytokines, tumor necrosis factor‐α and interleukin‐1β, were increased in the sciatic nerves of the diabetic rats. DPSC transplantation significantly decreased monocytes/macrophages and tumor necrosis factor‐α messenger ribonucleic acid expression, and increased the gene expression of the M2 macrophage marker, CD206, in the sciatic nerves of the diabetic rats. The in vitro study showed that DPSC‐conditioned media significantly increased the gene expressions of interleukin‐10 and CD206 in lipopolysaccharide‐stimulated RAW264.7 cells. CONCLUSIONS: These results suggest that DPSC transplantation promoted macrophages polarization towards anti‐inflammatory M2 phenotypes, which might be one of the therapeutic mechanisms for diabetic polyneuropathy. John Wiley and Sons Inc. 2015-12-31 2016-07 /pmc/articles/PMC4931198/ /pubmed/27181261 http://dx.doi.org/10.1111/jdi.12452 Text en © 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Omi, Maiko
Hata, Masaki
Nakamura, Nobuhisa
Miyabe, Megumi
Kobayashi, Yasuko
Kamiya, Hideki
Nakamura, Jiro
Ozawa, Shogo
Tanaka, Yoshinobu
Takebe, Jun
Matsubara, Tatsuaki
Naruse, Keiko
Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
title Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
title_full Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
title_fullStr Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
title_full_unstemmed Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
title_short Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
title_sort transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931198/
https://www.ncbi.nlm.nih.gov/pubmed/27181261
http://dx.doi.org/10.1111/jdi.12452
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