549-P: Transplantation of Human Dental Pulp Stem Cells Ameliorates Diabetic Polyneuropathy via Increasing Angiogenic and Neurotrophic Gene Expression in the Transplanted Muscles

Abstract

Transplantation of cryopreserved DPSCs ameliorated diabetic neuropathy equal to freshly isolated DPSCs. Human DPSCs (hDPSCs) can be isolated from teeth extracted at a young age and can be cryopreserved until use. The aim of this study is to clarify the therapeutic mechanism of hDPSCs transplantation on diabetic polyneuropathy. We collected human impacted third molars from adult at Aichi-Gakuin University hospital. Written informed consent was obtained from each donor. Identification of hDPSCs was analyzed by FACS and differentiation capabilities. Diabetes was induced by injection of STZ in 6 week-old BALB/cAJcl-nu/nu mice. Eight weeks after STZ injection, hDPSCs were transplanted into unilateral hindlimb skeletal muscles of normal and diabetic mice. Four weeks after transplantation, sciatic blood flow (SNBF), sciatic motor/sensory nerve conduction velocity (MNCV/SNCV) and current perception threshold (CPT) were assessed. To elucidate the therapeutic effects of hDPSCs, diabetic mice were treated with neutralizing antibody soon after transplantation. Immunohistological and gene expression analysis of hindlimb skeletal muscles were also performed at the end of the experiments. Diabetic mice showed significant reductions in SNBF, MNCV and SNCV and increase in CPTs in the control side compared with normal mice. Transplantation of hDPSCs significantly ameliorated the impaired SNBF, MNCV, SNCV and CPTs in the hDPSCs-injected side. The transplanted hDPSCs were located around the muscle bundles and expressed the human VEGF and NGF genes. Capillary/muscle bundle ratio was also increased in the hDPSCs-injected side. Furthremore, the effects of hDPSCs transplantation were cancelled by neutralizing antibodies of VEGF and NGF. These results suggest that cell therapy using hDPSCs may be useful for treatment of diabetic neuropathy via the angiogenic and neurotrophic factor by hDPSCs secretion. Disclosure M. Hata: None. M. Omi: None. N. Nakamura: None. M. Miyabe: None. M. Ito: None. E. Makino: None. S. Kanada: None. T. Ono: None. Y. Imanishi: None. T. Himeno: None. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehlinger Ingelheim Japan Co., Ltd., Daiichi Sankyo, Eli Lilly Japan K.K., Japan Tobacco Inc., Kaken Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Abbott Japan Co., Ltd., ARKRAY, Astellas Pharma Inc., AstraZeneca K.K., Boehlinger Ingelheim Japan Co., Ltd.,, Daiichi Sankyo, Eli Lilly Japan K.K., Fukuda Denshi, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Mylan, Novartis Pharma K.K., Novo Nordisk Pharma Ltd, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim K.K., Daiichi Sankyo, Eli Lilly Japan K.K., Fukuda Denshi, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. S. Ozawa: None. J. Takebe: None. T. Matsubara: None. K. Naruse: None.