Open AccessTransplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy
Author(s) -
Omi Maiko,
Hata Masaki,
Nakamura Nobuhisa,
Miyabe Megumi,
Kobayashi Yasuko,
Kamiya Hideki,
Nakamura Jiro,
Ozawa Shogo,
Tanaka Yoshinobu,
Takebe Jun,
Matsubara Tatsuaki,
Naruse Keiko
Publication year - 2016
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12452
Subject(s) - medicine , sciatic nerve , transplantation , dental pulp stem cells , tumor necrosis factor alpha , inflammation , nerve conduction velocity , streptozotocin , endocrinology , lipopolysaccharide , macrophage polarization , diabetes mellitus , macrophage , pathology , in vitro , mesenchymal stem cell , biology , biochemistry
Abstract Aims/Introduction Dental pulp stem cells ( DPSC s) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSC s 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 DPSC s were isolated from the dental pulp of Sprague–Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection, DPSC s were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation, neurophysiological measurements, inflammatory gene expressions and the number of CD 68‐positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of DPSC s, the effects of DPSC ‐conditioned media on lipopolysaccharide‐stimulated murine macrophage RAW 264.7 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 CD 68‐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, CD 206, 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 CD 206 in lipopolysaccharide‐stimulated RAW 264.7 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.