Development of MXene Composite Nanofiber-Based 3D Culture System for the Efficient Generation of MSC-Derived Functional Pancreatic β-Cells

ACS Appl Mater Interfaces. 2024 Dec 11;16(49):67514-67522. doi: 10.1021/acsami.4c17990. Epub 2024 Nov 26.

Abstract

Pancreatic β-cell transplantation is an effective approach for the therapeutic treatment of type I diabetes. However, it has limitations due to the lack of human cadaveric pancreas donors. Stem cells provide an alternative source for the generation of surrogate pancreatic β-cells. Nonetheless, its clinical utility is restricted due to the unavailability of a robust culture system for the generation of large quantities of insulin-responsive pancreatic β-cells. In this study, we fabricated an MXene composite nanofibrous scaffold (PCL 25_Ti2C 5 nanofiber) for the development of a three-dimensional (3D) culture system that can enhance the proliferation and differentiation of stem cell-derived pancreatic β-cells. The fabricated MXene composite nanofibers exhibited a porous nanostructure and increased hydrophilicity due to a large number of hydrophilic functional groups. We assessed the biocompatibility and differentiation potential of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) on a fabricated MXene composite nanofibrous scaffold. MXene composite nanofibers significantly upregulated key pancreatic β-cell markers including PDX-1, MAFA, Insulin, Nkx6.1, and Nkx2.2 and also showed increased production and secretion of insulin in response to glucose stimulation when compared to control (PCL 25 nanofiber), suggesting enhanced differentiation of hWJ-MSCs into functional pancreatic β-cells. Overall, the results suggest that MXene nanofiber-based cell therapy has therapeutic potential for diabetes treatment.

Keywords: 2D MXene; composite nanofibers; differentiation; mesenchymal stem cells (MSCs); pancreatic β-cells.

MeSH terms

  • Cell Culture Techniques, Three Dimensional
  • Cell Differentiation* / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells* / cytology
  • Insulin-Secreting Cells* / drug effects
  • Insulin-Secreting Cells* / metabolism
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Nanofibers* / chemistry
  • Nuclear Proteins
  • Tissue Scaffolds* / chemistry
  • Transcription Factors

Substances

  • Homeobox Protein Nkx-2.2
  • NKX2-2 protein, human
  • Insulin
  • Nuclear Proteins
  • Transcription Factors
  • Homeodomain Proteins