Human urine-derived stem cells play a novel role in the treatment of STZ-induced diabetic mice

J Mol Histol. 2018 Aug;49(4):419-428. doi: 10.1007/s10735-018-9772-5. Epub 2018 Apr 19.

Abstract

Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ). Serum and pancreatic insulin were measured, islet morphology and its vascularization were investigated. hUSCs highly expressed CD29, CD73, CD90 and CD146, and could differentiate into, at least, bone and fat in vitro. Transplantation of hUSCs into HD-STZ treated mice prolonged the median survival time and improved their blood glucose, and into those with MLD-STZ improved the glucose tolerance, islet morphology and increased the serum and pancreas insulin content. Furthermore, CD31 expression increased significantly in islets of BALB/c nude mice treated with hUSCs compared to those of un-transplanted MLD-STZ mice. hUSCs could improve the median survival time and glucose homeostasis in STZ-treated mice through promoting islet vascular regeneration and pancreatic beta-cell survival.

Keywords: Angiogenesis; Cell therapy; Diabetes; Human urine-derived stem cells.

MeSH terms

  • Adult
  • Animals
  • Blood Glucose / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cell Shape
  • Cell Survival
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Streptozocin
  • Urine / cytology*

Substances

  • Blood Glucose
  • Insulin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Streptozocin