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Project

Deep phenotyping of cellular heterogeneity and maturation in human iPSC-derived brain organoids and cardiomyocytes.

Pluripotent stem cell (PSC) technology is increasingly gaining interest for modelling diseases and developing precision therapeutics. However, the immaturity and heterogeneity of PSC-derived cell populations impinge on the reproducibility and preclude their use for comparative and diagnostic analyses. Recognizing these caveats for their own human induced (hi)PSC-based research, the Laboratories of Experimental Hematology, Cardiogenetics and Cell Biology and Histology have teamed up to develop a pipeline that enables accurate phenotypic staging of hiPSC-derived cell culture models. Specifically, to create mature and standardized 2D and 3D-models for cardiomyocyte cultures and brain organoids, our consortium proposes to optimize the culture conditions and refine the interrogation methods. Longitudinal follow-up and validation of functional activity in the differentiation products will be achieved by means of high-throughput multi-electrode array recordings and live cell calcium and voltage imaging. In parallel, cellular heterogeneity will be mapped with quantitative immunofluorescence and transcriptome analyses. The correlation of functional and molecular readouts will allow establishing a biomarker panel for mature hiPSC-derived cardiomyocyte models and brain organoids. Thus, with this work, we intend to develop more reproducible models and to allow selecting only those with the highest functional maturity, a prerequisite for our future stem cell research aimed at studying and treating neuro-inflammatory and cardiogenetic disorders.
Date:1 Jan 2021 →  Today
Keywords:CARDIOMYOCYTES, STEM CELLS
Disciplines:Tissue engineering, Stem cell biology