Insulin producing cells generation by overexpression of miR-375 in adipose-derived mesenchymal stem cells from diabetic patients

Biologicals. 2017 Mar:46:23-28. doi: 10.1016/j.biologicals.2016.12.004. Epub 2016 Dec 22.

Abstract

Diabetes Mellitus (DM) is a systematic disease, which happens because of destruction of islets of Langerhans in the pancreas and systematic resistance to insulin. The lack of donor for pancreas transplantation and risk of transplant rejection is the main challenge in the treatment of this disease. Stem cells are proper and sufficient source for creating insulin-producing cells (IPC). In this study adipose tissue was provided from diabetic patients operated for liposuction and then adipose derived stem cells (ADSCs) were isolated, characterized and then treated by lentiviruses containing miR-375, after 7, 14 and 21 days of induction, islet-like clusters (ILC) specific genes including insulin and PDX1 were evaluated by Real Time RT-PCR. Finally, immunocytochemistry was also used for evaluation of these markers in the protein level. The results were shown that insulin and PDX1 genes and proteins expression significantly increased in transduced stem cells compared to the control group. According to the results it can be concluded that islet-like clusters can be achieved from ADSCs by overexpression of miR-375.

Keywords: Adipose derived stem cells; Insulin-producing cells; MicroRNA; PDX1.

MeSH terms

  • Adipose Tissue / pathology
  • Adult
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Gene Expression
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism*
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics*
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Homeodomain Proteins
  • Insulin
  • MIRN375 microRNA, human
  • MicroRNAs
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein