Insights into Islet Differentiation and Maturation through Proteomic Characterization of a Human iPSC-Derived Pancreatic Endocrine Model.

PURPOSE: Great progresses have been made for generating in vitro pluripotent stem cell pancreatic ß-like cells. However, the maturation stage of the cells still requires in vivo maturation to recreate the environmental niche. A deeper understanding of the factors promoting maturation of the cells is of great interest for clinical applications. EXPERIMENTAL DESIGN: Label-free mass spectrometry based proteomic analysis is performed on samples from a longitudinal study of differentiation of human induced pluripotent stem cells toward glucose responsive insulin producing cells. RESULTS: Proteome patterns correlate with specific transcription factor gene expression levels during in vitro differentiation, showing the relevance of the technology for identification of pancreatic-specific markers. The analysis of proteomes of the implanted cells in a longitudinal study shows that the neovascularization process linked to the extracellular matrix environment is time-dependent and conditions the proper maturation of the cells in ß-like cells secreting insulin in response to glucose. CONCLUSIONS AND CLINICAL RELEVANCE: Proteomic profiling is valuable to qualify and better understand in vivo maturation of progenitor cells toward ß-cells. This is critical for future clinical trials where in vivo maturation still needs to be improved for robustness and effectiveness of cell therapy. Novel biomarkers for predicting the efficiency of maturation represents noninvasive monitoring tools for following efficiency of the implant.