Pluripotency & Regeneration

Pluripotent cells possess the ability to both proliferate indefinitely and differentiate towards any cells that constitute an adult body. Since the discovery of induced pluripotency in 2006, induced pluripotent stem cells (iPSCs) have become a powerful tool for biomedical research and hold great promise for regenerative medicine. The working group Pluripotency & Regeneration investigates the cellular mechanisms that maintain and modulate pluripotency, using human iPSCs and the freshwater planarian Schmidtea mediterranea as model systems.

The group has three work units:

Human iPSCs-derived Organoids

The aim of this work unit is to develop protocols for the production of human iPSC-derived organoids. Owing to their extreme plasticity, hiPSCs and their derivatives could be used for drug discovery, disease modeling, toxicity test and therapy. Current pitfalls in the generation of human organoids are the immaturity of the hiPSC-derived cells and the low complexity of the organoids. This results in a lack of functionality, which downgrades the potential of the model system. Therefore, on the one hand we aim to establish stable culture conditions for multipotent progenitor cells (e. g. Isl-1+ cardiac progenitor cells), on the other one, we use ultra-high viscosity (UHV) alginate to create 3D, cell-instructing scaffolds to improve cell maturation compared to rigid plastic substrates.

In order to guarantee the supply of biological material for research, diagnostic and therapeutic purposes, we collaborate with the working group Cryobiotechnology on novel cryopreservation protocols based on vitrification, for the cryopreservation of cell-scaffold complexes.

Development of New Substrates

Cells are highly sensitive to the physical and (bio)chemical properties of the micro-environment. This multidisciplinary work unit designs innovative and smart materials to mimic and understand the cellular milieu and its potential to direct cell behaviour, such as adhesion, proliferation, migration and differentiation. To investigate defined cell-matrix interactions, the group takes advantage of the unique features of UHV alginate, which combines unique structural characteristics and the highest biocompatibility. Using a variety of surface functionalization techniques, specific cellular environments are engineered for two- and three-dimensional approaches. The development of sophisticated labware and the automation of reproducible 3D culture using microfluidic-based pipette robots complete this biotechnological workflow which finds broad application in research.  

Pluripotency-based Regeneration

Pluripotent stem have an unbeatable potential to self-renew and repair damaged tissues. Planarians – uniquely in the animal kingdom – possess a large population of pluripotent stem cells on which their extraordinary regeneration ability hinges upon. Thanks to this unique feature, we can study pluripotency in vivo in the adult in order to understand how pluripotent stem cells in planarians form tissues and organs where in any other adult Bilateria form tumors.

A critical question is how stem cells exit self-renewal and commit towards a defined lineage. To elucidate this, we focus on the changes of the ground state of pluripotency, investigating on the molecular mechanisms that influence the transition from naïve to primed state. Using fluorescent in vivo cell tracing in combination with single-cell gene expression, immunocytochemistry and flow cytometry, we aim to gain insights into pluripotency-based regeneration, for future therapeutic approaches in human. 

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