Proteomics Clin Appl. 2018 Mar 26:e1600173. doi: 10.1002/prca.201600173. [Epub ahead of print]

Insights into islet differentiation and maturation through proteomic characterization of a human iPSC-derived pancreatic endocrine model.

Haller C¹, Chaskar P¹, Piccand J¹, Cominetti O², Macron C², Dayon L², Kraus MR¹.

Abstract

PURPOSE:

Great progresses have been made for generating in vitro pluripotent stem cell pancreatic β-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:

We performed label-free mass spectrometry-based proteomic analysis of samples from a longitudinal study of differentiation of human-induced pluripotent stem cells towards glucose-responsive insulin producing cells.

RESULTS:

Proteome patterns correlated with specific transcription factor gene expression levels during in vitro differentiation, showing the relevance of the technology for identification of pancreatic-specific markers. We analyzed proteomes of the implanted cells in a longitudinal study and showed that the neovascularization process linked to the extracellular matrix environment is time-dependent and conditions the proper maturation of the cells in β-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 towards β-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 non-invasive monitoring tools for following efficiency of the implant. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.