Transplantation of human dental pulp stem cells ameliorates diabetic polyneuropathy in streptozotocin-induced diabetic nude mice: the role of angiogenic and neurotrophic factors

Autor: Yasuko Kobayashi, Eriko Makino, Shigemi Goto, Megumi Miyabe, Jun Takebe, Hideki Kamiya, Kenichi Kurita, Maiko Omi, Tomokazu Saiki, Tatsuaki Matsubara, Tatsuhito Himeno, Shogo Ozawa, Yuka Imanishi, Masaki Hata, Nobuhisa Nakamura, Jiro Nakamura, Saki Kanada, Keiko Naruse, Tasuku Ohno, Ken Miyazawa, Mizuho Ito
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Diabetic polyneuropathy
Medicine (miscellaneous)
Mice
Nude
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Cell therapy
Streptozocin
Diabetes Mellitus
Experimental
lcsh:Biochemistry
Rats
Sprague-Dawley
chemistry.chemical_compound
Mice
Diabetic Neuropathies
Neurotrophic factors
Internal medicine
Dental pulp stem cells
medicine
Animals
Humans
lcsh:QD415-436
Cells
Cultured
Dental Pulp
NGF
lcsh:R5-920
biology
business.industry
Research
Stem Cells
Diabetes
Cell Differentiation
Cell Biology
VEGF
Rats
Vascular endothelial growth factor
Transplantation
Human dental pulp stem cells (hDPSCs)
Nerve growth factor
Endocrinology
chemistry
Regenerative medicine
biology.protein
Molecular Medicine
Sciatic nerve
Stem cell
business
lcsh:Medicine (General)
Neurotrophin
Zdroj: Stem Cell Research & Therapy
Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-11 (2020)
ISSN: 1757-6512
Popis: Background Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. In our previous study, we demonstrated that cryopreserved rat DPSCs improved diabetic polyneuropathy and that the efficacy of cryopreserved rat DPSCs was equivalent to that of freshly isolated rat DPSCs. The present study was conducted to evaluate whether transplantation of cryopreserved human DPSCs (hDPSCs) is also effective for the treatment of diabetic polyneuropathy. Methods hDPSCs were isolated from human impacted third molars being extracted for orthodontic reasons. Eight weeks after the induction of diabetes in nude mice, hDPSCs (1 × 105/limb) were unilaterally transplanted into the hindlimb skeletal muscle, and vehicle (saline) was injected into the opposite side as a control. The effects of hDPSCs were analyzed at 4 weeks after transplantation. Results hDPSC transplantation significantly ameliorated reduced sensory perception thresholds, delayed nerve conduction velocity, and decreased the blood flow to the sciatic nerve in diabetic mice 4 weeks post-transplantation. Cultured hDPSCs secreted the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) proteins. A subset of the transplanted hDPSCs was localized around the muscle bundles and expressed the human VEGF and NGF genes at the transplanted site. The capillary/muscle bundle ratio was significantly increased on the hDPSC-transplanted side of the gastrocnemius muscles in diabetic mice. Neutralizing antibodies against VEGF and NGF negated the effects of hDPSC transplantation on the nerve conduction velocity in diabetic mice, suggesting that VEGF and NGF may play roles in the effects of hDPSC transplantation on diabetic polyneuropathy. Conclusions These results suggest that stem cell transplantation with hDPSCs may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors.
Databáze: OpenAIRE
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