The effect of exosomes derived from mesenchymal stem cells in the treatment of induced type 1 diabetes mellitus in rats

Biotechnol Lett. 2020 Aug;42(8):1597-1610. doi: 10.1007/s10529-020-02908-y. Epub 2020 May 19.

Abstract

Aim: The aim of the current study was to evaluate the therapeutic and regenerative effects of MSCs derived exosomes in the treatment of type 1 DM and to compare its effects with MSCs themselves. The experiment was done on forty albino rats grouped as follows, group (1): Ten healthy rats, group (2): Ten induced type 1 DM rats, group (3): Ten induced type 1 DM rats received exosomes intraperitoneally, and group (4): Ten induced type 1 DM rats received MSCs intraperitoneally. Serum glucose and plasma insulin levels were assessed weekly. QRT-PCR was done to assess regeneration of pancreatic beta cells by measuring insulin, Pdx1, Smad2, Smad3 and TGFβ genes. Additionally, histopathological and immune-histochemical examinations were done to confirm pancreatic tissue regeneration.

Results: Regarding the assessed genes (insulin, Pdx1, Smad2, Smad3 and Tgfβ) gene expression in MSCs treated group showed significant increase compared to diabetic group (p value < 0.001) and gene expression in exosomes treated group was increased significantly compared to diabetic and MSCs treated groups (p value < 0.001). Histopathological and immune-histochemical examination revealed regeneration of pancreatic islets in both treated groups.

Conclusion: MSCs Derived exosomes showed superior therapeutic and regenerative results than MSCs themselves.

Keywords: Exosomes; Insulin; MSCs; Pdx1; Smad2; Smad3; Tgfβ; Type 1 DM.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 1 / metabolism*
  • Exosomes / chemistry
  • Exosomes / metabolism*
  • Female
  • Homeodomain Proteins / metabolism
  • Insulin / blood
  • Insulin / metabolism
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • Rats
  • Smad1 Protein / metabolism
  • Smad2 Protein / metabolism
  • Trans-Activators / metabolism

Substances

  • Blood Glucose
  • Homeodomain Proteins
  • Insulin
  • Smad1 Protein
  • Smad1 protein, rat
  • Smad2 Protein
  • Smad2 protein, rat
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein