Transplantation of stem cells obtained from murine dental pulp improves pancreatic damage, renal function, and painful diabetic neuropathy in diabetic type 1 mouse model.
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.
Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Bahia, Brazil.
Elisalva Teixeira
ET
Guimarães
Gabriela da Silva
Gda S
Cruz
Tiago Farias de
TF
Almeida
Bruno Solano de Freitas
BS
Souza
Carla Martins
CM
Kaneto
Juliana Fraga
JF
Vasconcelos
Washington Luis Conrado dos
WL
Santos
Ricardo Ribeiro-dos
RR
Santos
Cristiane Flora
CF
Villarreal
Milena Botelho Pereira
MB
Soares
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003404:Creatinine / Q000097:blood; D003782:Dental Pulp / Q000166:cytology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000473:pathology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013311:Streptozocin; D014508:Urea / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D014508:Urea; D003404:Creatinine