Small Molecule Differentiate PDX1-Expressing Cells Derived from Human Endometrial Stem Cells on PAN Electrospun Nanofibrous Scaffold: Applications for the Treatment of Diabetes in Rat

Mol Neurobiol. 2020 Sep;57(9):3969-3978. doi: 10.1007/s12035-020-02007-z. Epub 2020 Jul 7.

Abstract

In this study, we designed an engineered tissue and transplanted it to an animal model, trying to take an effective step toward meeting the needs of diabetic patients. Here, human endometrial cells were differentiated into PDX1-expressing cells using a small molecule of Y-27632 on polyacrylonitrile (PAN) electrospun scaffolds and transplanted into diabetic rats. PAN nanofibers were made by electrospinning. RT-PCR and immunocytochemical analysis were performed to express pancreatic precursor (PP) genes. The differentiated cells were then transplanted into the abdominal cavity of diabetic rats with Streptozotocin. In another group of rats, differentiated cells were injected through the tail. Blood glucose was measured 7, 14, and 28 days after transplantation, and rat weight was also measured. The results showed that the expression of PP markers including Sox-17, Ngn3, Pdx1, and NKx2.2 genes was significantly increased in differentiated cells compared to the control group. In diabetic rats receiving differentiated cells, both transplanted and injected, glucose concentration as well as body weight improved compared to the control group. Rats receiving transplants in the peritoneum had a lower blood glucose concentration than those in the cell receiving group by injection, and the cell receiving group in the form of injections was more effective in increasing the body weight of rats than in the other groups. According to the results of the study, the transplantation of PP from endometrium using PAN scaffolding at the site of peritoneum could be recommended for the treatment of diabetes, although further studies are needed to provide a complete cure.

Keywords: Beta precursor cells; Diabetes; Human uterine endometrial cells; Nanofibers scaffold; Tissue engineering.

MeSH terms

  • Acrylic Resins / chemistry*
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Cell Differentiation
  • Cell Nucleus Shape
  • Cell Shape
  • Cell Survival
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / therapy*
  • Endometrium / cytology*
  • Female
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Nanofibers / chemistry*
  • Nanofibers / ultrastructure
  • Nuclear Proteins
  • Rats, Wistar
  • Small Molecule Libraries / pharmacology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Stem Cells / ultrastructure
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry*
  • Trans-Activators / metabolism*
  • Transcription Factors

Substances

  • Acrylic Resins
  • Blood Glucose
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • NKX2-2 protein, human
  • Nkx2-2 protein, rat
  • Nuclear Proteins
  • Small Molecule Libraries
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein
  • polyacrylonitrile