title: Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Omi
authors.affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hata
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Miyabe
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kamiya
authors.affiliation: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takebe
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
mesh_terms: D000818:Animals; D016764:Cell Polarity; D049109:Cell Proliferation; D002470:Cell Survival; D003782:Dental Pulp / Q000166:cytology / Q000637:transplantation*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000150:complications*; D004195:Disease Models, Animal; D008264:Macrophages / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009431:Neural Conduction; D009443:Neuritis / Q000209:etiology / Q000517:prevention & control / Q000601:surgery*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000503:physiopathology*
keywords: Cell transplantation; Dental pulp stem cells; Diabetic polyneuropathy