Transplantation of Stem Cells Obtained from Murine Dental Pulp Improves Pancreatic Damage, Renal Function, and Painful Diabetic Neuropathy in Diabetic Type 1 Mouse Model

Autor: Elisalva Teixeira Guimarães, Gabriela Da Silva Cruz, Tiago Farias De Almeida, Bruno Solano De Freitas Souza, Carla Martins Kaneto, Juliana Fraga Vasconcelos, Washington Luis Conrado Dos Santos, Ricardo Ribeiro-Dos-Santos, Cristiane Flora Villarreal, Milena Botelho Pereira Soares
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Cell Transplantation, Vol 22 (2013)
Druh dokumentu: article
ISSN: 0963-6897
1555-3892
DOI: 10.3727/096368912X657972
Popis: Diabetes mellitus (DM) is one of the most common and serious chronic diseases in the world. Here, we investigated the effects of mouse dental pulp stem cell (mDPSC) transplantation in a streptozotocin (STZ)-induced diabetes type 1 model. C57BL/6 mice were treated intraperitoneally with 80 mg/kg of STZ and transplanted with 1 × 10 6 mDPSCs or injected with saline, by an endovenous route, after diabetes onset. Blood and urine glucose levels were reduced in hyperglycemic mice treated with mDPSCs when compared to saline-treated controls. This correlated with an increase in pancreatic islets and insulin production 30 days after mDPSC therapy. Moreover, urea and proteinuria levels normalized after mDPSC transplantation in diabetic mice, indicating an improvement of renal function. This was confirmed by a histopathological analysis of kidney sections. We observed the loss of the epithelial brush border and proximal tubule dilatation only in saline-treated diabetic mice, which is indicative of acute renal lesion. STZ-induced thermal hyperalgesia was also reduced after cell therapy. Three days after transplantation, mDPSC-treated diabetic mice exhibited nociceptive thresholds similar to that of nondiabetic mice, an effect maintained throughout the 90-day evaluation period. Immunofluorescence analyses of the pancreas revealed the presence of GFP + cells in, or surrounding, pancreatic islets. Our results demonstrate that mDPSCs may contribute to pancreatic β-cell renewal, prevent renal damage in diabetic animals, and produce a powerful and long-lasting antinociceptive effect on behavioral neuropathic pain. Our results suggest stem cell therapy as an option for the control of diabetes complications such as intractable diabetic neuropathic pain.
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