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TRANSPLANTATION OF STEM CELLS OBTAINED FROM MURINE DENTAL PULP IMPROVES PANCREATIC DAMAGE, RENAL FUNCTION, AND PAINFUL DIABETIC NEUROPATHY IN DIABETIC TYPE 1 MOUSE MODEL
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Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Abstract
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 ´ 106 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 salinetreated
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 b-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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