NKX6.1 combined with PDX1 induces mesenchymal stem cell differentiation into B-like cells / 第二军医大学学报

ABSTRACT

Objective To study the synergistic effect of NKX6. 1 and PDX1 in inducing differentiation of fetal liver-derived mesenchymal stem cells(FL-MSCs) into the pancreatic B cells and to explore the underlying mechanisms, so as to obtain enough islet-like body for transplantation. Methods Recombinant adenovirus vector harboring both PDX1 and NKX6. 1 genes was constructed, and the vector was used to infect FL-MSCs. Then a series of cytokines were used to induce the differentiation of infected FL-MSCs into pancreatic B cells. The expressions of PDX1, NKX6.1 gene, transcription factors NGN3, NeuroDl/Beta2, MafA as well as C-peptide were examined. Results PDX1 and NKX6. 1 were detected in FL-MSCs cells 24 h after infection; cells began to express NGN3, NeuroDl, and MafA and stably expressed pancreatic B cell related factors including insulin after induction. The expression of these molecules was in a certain order. Conclusion PDX1, NKX6. 1 combined with a series of cytokines can effectively induce FL-MSCs to differentiate into pancreatic islet B cells in vitro, which might be through activation of transcription factors NGN3, NeuroDl, and MafA in turn, inducing FL-MSCs to differentiate towards endocrine precursor cells, B endocrine precursor cells and B cells in turn.