Research Stijn in 't Groen

Abstract

Neuromuscular disorders (NMDs) encompass a diverse group of diseases that severely impact patients' quality of life and reduce life expectancy. Despite the urgent need, only a handful of these disorders are currently treatable. A major barrier to therapeutic development is the lack of humanized models that can accurately reflect the complex neuromuscular phenotypes observed in patients. Recent advancements in cell culture techniques have enabled the development of functional 3D-tissue-engineered skeletal muscles (3D-TESMs), offering a promising platform to study NMDs. However, the integration of motor neurons and neuromuscular junctions (NMJs) in these models remains challenging. In this project, I will develop innervated 3D-TESM models capable of contractile functioning using human-induced pluripotent stem cell-derived muscle cells and motor neurons. By integrating 3D-printing technologies and a customized high-density multielectrode array, I plan to generate two innervated 3D-TESM cell models to study both the muscular and neuronal aspects of NMDs. As a proof-of-concept, these models will be applied to study the effects of axonal Charcot- Marie-Tooth disease (CMT2), illustrating their potential for investigating NMDs. Overall, the development of innervated 3D-TESMs will represent a significant step forward in creating more accurate humanized systems to study NMDs and accelerate the development of effective therapeutics.

Researcher(s)

• Promoter: Timmerman Vincent
• Fellow: in 't Groen Stijn

Research team(s)

• Peripheral Neuropathies Group

Project type(s)

• Research Project

Abstract

This application is to request funding to purchase a state-of-the-art 3D Multi-Electrode Array platform (MEA) to enable electrophysiological recordings from complex electrically excitable tissues and organoids. To study the electrophysiological properties of excitable cells, patch-clamping is deemed the gold-standard, but it is an extremely labor-intensive and invasive technique and limited to short-term measurements of individual or small numbers of cells at a single time point. In contrast, MEAs enable high-throughput non-invasive longitudinal real‐time measurements of functional cellular networks without disrupting important cell-cell contacts whilst allowing for the recording of many hundreds to thousands of cells simultaneously therefore providing greater insight into important physiological processes. Current MEA systems at the University of Antwerp only include setups using arrays of planar electrodes which are not suitable for recording from the complex tissues such as brain and cardiac organoids or tissue sections as the electrodes do not get close to the active cells. In contrast this 3D MEA system consists of arrays of ~0.1 mm raised electrodes which allow for repeated recordings from active cells within these organoids and tissues which can be grown under various experimental conditions. There is an urgent need as increasing numbers of research groups at the University of Antwerp use such tissue models but have no means to record from them. The 3D MEA platform is the most suitable instrument and will help many groups to functionally elucidate the pathomechanisms of neurological and cardiac disorders as well as provide the opportunity to rapidly screen large drug libraries.

Researcher(s)

• Promoter: Ellender Tommas
• Co-promoter: Bittremieux Wout
• Co-promoter: in 't Groen Stijn
• Co-promoter: Weckhuysen Sarah

Research team(s)

• Experimental Neurobiology Unit (ENU)

Project type(s)

• Research Project