Generation of insulin-producing cells from human adipose-derived mesenchymal stem cells on PVA scaffold by optimized differentiation protocol

J Cell Physiol. 2018 May;233(5):4327-4337. doi: 10.1002/jcp.26266. Epub 2017 Dec 26.

Abstract

The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels. The viability of induced pancreatic cells was 14 days. The in vitro studies showed that the treatment of hADSCs in the 3D culture resulted in differentiated cells with strong characteristics of IPCs including pancreatic-like cells, the expression of the islet-associated genes at the mRNA and protein levels in comparison of 2D culture group. Furthermore, the immunoassay tests showed that these differentiated cells in these two groups are functional and secreted C-peptide and insulin in a glucose stimulation challenge. The results of our study for the first time demonstrated that the PVA nanofibrous scaffolds along with the optimized differentiation protocol with PRP can enhance the differentiation of IPCs from hADSCs. In conclusion, this study provides a new approach to the future pancreatic tissue engineering and beta cell replacement therapies for T1DM.

Keywords: 3D culture; insulin-producing cells; mesenchymal stem cells; platelet-rich plasma; polyvinyl alcohol.

MeSH terms

  • Adipocytes / metabolism
  • Adult
  • Blood Donors
  • C-Peptide / genetics*
  • C-Peptide / metabolism
  • Cell Culture Techniques
  • Cell Differentiation / genetics
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy*
  • Gene Expression Regulation / genetics
  • Glucose / metabolism
  • Humans
  • Insulin / biosynthesis*
  • Insulin / genetics
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / metabolism
  • Mesenchymal Stem Cells / metabolism
  • Platelet-Rich Plasma / metabolism
  • Polyvinyl Alcohol / chemistry
  • Polyvinyl Alcohol / metabolism
  • Tissue Scaffolds / chemistry

Substances

  • C-Peptide
  • Insulin
  • Polyvinyl Alcohol
  • Glucose