Periodic Reporting for period 1 - CISTEM (Heart On chip based on induced pluripotent Stem cell Technology for personalized Medicine)
Reporting period: 2018-01-01 to 2019-12-31
• Engineering Heart –on-chip from Cardiomyocytes-derived hiPSCs using microfluidic and microsystem technologies
• Use of the developed platform to model and investigate the cardiomyopathy coming from the Duchenne muscular dystrophy.
In addition, CISTEM project aims also to implement a high quality staff exchange programme in order to :
• Connect high-quality research infrastructures using them as training facilities for developing and completing the skills of the CISTEM’participants
• Contribute to bridging the gap between industry and high education institutions by implementing a structured secondment-based exchange programme
• The establishment of a protocol for 3D surface functionalization
• Optimisation of the co-culture condition with fibroblasts and endothelial cells inside a microfluidic device.
• Differentiation of iPSCs into cardiomyocytes
• Development of a perfusion station for investigating the shear stress effect on the maturation of cardiomyocytes
• Preliminary investigation of the shear stress effect on the maturation of CM-iPSC
• Development of electronic modules for TEER measurement and electrical stimulation
• Fabrication of heart membrane for mechanical stretch for mechanical actuation
The scientific results have been generated through the secondments/return phases of CISTEM secondees. The secondees have participated in many training activities for acquiring knowledge related to the project research activities such as cell culture protocols and procedures, surface functionalisation, cell culture characterization, microfluidic and microfabrication.
Career development of secondees is also an important objective of CISTEM which has been achieved through training, transfer of knowledge and networking activities, both inter-sectoral and intercontinental, mainly by means of secondment visits and workshop. CISTEM has offered a good opportunity for the seconded persons to reinforce their respective CV, and to consolidate their laboratory and general skills.
After these 2 years, CISTEM became a sustainable international network of academics and SMEs who are collectively overcoming obstacles in the development of Heart-on-chip for personalised medicine. As mentioned before the network has already provided clear results towards this objective: 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. Secondly, iPSC-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). We expect that the developed techniques will offer significant advantage for accurately modelling rare diseases.
Apart from the research activities, CISTEM has already promoted joint research initiatives and new collaborative projects are stemming out of the network. In addition, the researchers involved in the project have established a new network that reaches far beyond their home organization and gathered additional skills and knowledge that will significantly contribute to advance their careers by opening new professional opportunities.