Genetic Rare Disorders such as Cardiomyopathy coming from Duchenne muscular dystrophy still represent an unmet medical need. Developing a heart model in a patient-match manner might contribute to a better understanding of mechanisms of cardiomyopathy that can provide better chance for patients, improving their conditions of life and prolonging its extent.
CISTEM became a sustainable international network of academics and SMEs who collectively worked in the development of Heart-on-chip for personalised medicine. As mentioned before the network has already provided clear results towards this objective: In the first period of the project, the CISTEM work has been focused on the optimisation of the culture condition of cardiomyocytes derived from iPSCs inside a microfluidic device. Different approaches have been evaluated and combined to improve cardiomyocyte viability and to reproduce the in-vivo environment inside the microfluidic device. Firstly, a robust protocol has been designed for 3D Surface functionalization of the device to reinforce the hydrogel attachment to the device and maintain the hydrogel architecture for a week. In addition, hiPSC-CM co-culture with human endothelial cells and fibroblasts was optimized to provide the CM-iPSc a more realistic cell culture environment which has shown to improve CM-iPSCs viability. Furthermore, to reproduce the dynamic condition of the in-vivo environment, a microfluidic set-up has been developed to generate controllable shear stress through the microfluidic device. Preliminary investigation has shown that the shear stress conditioning results in a change in cell morphology and an increase in vinculin production (protein needed for proper electrochemical signal transduction through cell-cell adhesion). In the second period, the consortium worked on the development and optimization of Heart-On-Chip platform using equipment and microfluidic devices provided by the industrial partners. Innovative approaches have been established to perform TEER measurement in microfluidic devices and multi-well disposables. Furthermore, the effective differentiation of DMD-derived hiPSC-cardiomyocytes, hiPSC-derived cardiac fibroblasts (hiPSC-CF) and hiPSC-derived endothelial cells (hiPSC-EC) has been achieved along with the formation of complex three-dimensional cardiac microtissues.
Apart from the research activities, CISTEM has already promoted joint research initiatives and new collaborative projects have been generated from the network. In addition, the researchers involved in the project have gathered additional skills, knowledge and know-how that will significantly contribute to advance their careers by opening new professional opportunities.
