Electrospun Poly-L-lactic acid/poly Vinyl Alcohol Nanofibers Improved Insulin-Producing Cells Differentiation Potential of HumanAdipose Derived-Mesenchymal Stem Cells

Background and Aim: Pancreatic differentiation of stem cells will aidtreatment of patients with type I diabetes mellitus (T1DM). Syntheticbiopolymers utilization provided extracellular matrix (ECM) and desiredattributes in vitro to enhance conditions for stem cells proliferation,attachment, and differentiation. A mixture of polycaprolactone andpolyvinyl alcohol (PCL/PVA)-based scaffold, could establish an in vitrothree-dimensional (3D) culture model.Methods: The objective of this study was investigation of the humaninduced pluripotent stem cells (hiPSCs) differentiation capacity to insulinproducingcells (IPCs) in 3D culture were compared with conventionalculture (2D) groups evaluated at the mRNA and protein levels by RTqPCRand immunofluorescence assay, respectively. The functionality ofdifferentiated IPCs was evaluated by C-peptide and insulin release inresponse to glucose stimulation test.Results: Real-time RT-PCR results showed that iPSCs-IPCs expressedpancreas-specific transcription factors (Insulin, Pdx1, Glucagon, Glut2,and Ngn3). The expressions of these transcription factors in PCL/PVAscaffold were higher than 2D groups. In addition to IPCs specific markerswere detected by immunochemistry. These cells in both groups secretedinsulin and C-peptide in a glucose challenge test by ELISA showing invitro maturation.Results: Real-time RT-PCR results showed that iPSCs-IPCs expressedpancreas-specific transcription factors (Insulin, Pdx1, Glucagon, Glut2,and Ngn3). The expressions of these transcription factors in PCL/PVAscaffold were higher than 2D groups. In addition to IPCs specific markerswere detected by immunochemistry. These cells in both groups secretedinsulin and C-peptide in a glucose challenge test by ELISA showing invitro maturation.Conclusion: The results of the current study demonstrated that the PCL/PVA nanofibrous scaffolds can enhance the differentiation of IPCs fromhiPSCs. In conclusion, this research could provide a new approach forbeta cell replacement therapies and pancreatic tissue engineering forT1DM in the future.

کلیدواژه ها:

Adipose-derived mesenchymal stem cells ، Poly-L-lactic acid/ polyvinyl alcohol ، Scaffold ، Insulin-producing cells ، Differentiation