Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - TECHNOBEAT (Tools and TECHNOlogies for Breakthrough in hEArt Therapies)

Teaser

Ischemic heart diseases diseases including myocardial infarction (MI), which entails the irreversible loss of function heart muscle tissue, constitute a major socio-economic burden in global healthcare. The costs related to sickness, morbidity and the productivity losses...

Summary

Ischemic heart diseases diseases including myocardial infarction (MI), which entails the irreversible loss of function heart muscle tissue, constitute a major socio-economic burden in global healthcare. The costs related to sickness, morbidity and the productivity losses resulting from ischemic heart diseases alone amounts to about €45 billion/year in the EU (http://www.who.int/cardiovascular_diseases/en/).
Consequently, the overall objective of the project is developing innovative tools and technologies enabling a curative, cell-based therapy for damaged hearts. Achieving this goal will have a considerable socio-economic impact on Europe’s healthcare system and on patients’ personal well-being.
Through its interdisciplinary excellence, TECHNOBEAT’s consortium of leading European stem cell researchers, clinicians, tissue-, bioprocess-, and technical- engineers in industry and academia is ideally positioned to address this ambitious objective(s).
Currently, heart transplantation is the only treatment option for end-stage heart failure patients; this option is strongly restricted by the availability of donor organs and the requirement of life-long medication with immunosuppressing drugs. In contrast, TECHNOBEAT aims at establishing advanced cell therapies aimed at the functional reconstitution of damaged hearts thereby preventing heart failure and the need for organ replacement.
Human induced pluripotent stem cells (hiPSCs) can be derived by a recent technology know as “reprogramming” from patients’ own somatic cells. hiPSCs have outstanding features with respect to their utility for advanced cell therapies that is an unlimited expandability and differentiation potential into all relevant cell types in a dish, including functional human cardiomyocytes (heart muscle cells), endothelial cells (lining the blood vessels), and connective tissue-forming cells. These features make hiPSC highly attractive as a universal cell source for organ repair. However, technologies for the robust production of hiPSC-derived progenies in line with GMP standards and at reasonable cost are currently lacking.
In more detail, TECHNOBEAT’s ultimate objectives are:
1) Advancing bioprocesses for therapeutic scale production of hiPSC and their functional cardiac progenies through innovative bioreactor technologies, process optimisation, and by novel cell monitoring tools.

2) Develop regulatory-compliant processing strategies for innovative, iPSC-progeny-derived cardiac μ-tissues which will be used as building blocks for heart repair.

3) Develop the clinical translation of cardiac μ-tissue for heart repair including: the development and application of tools for improved cell/ µ-tissue delivery to the heart and longitudinal in vivo monitoring of grafted cells.

4) Proof-of-concept for safety and functional integration of transplanted cells and tissues in physiologically relevant, preclinical models of heart failure.

Work performed

In the first 18 months of the project, TECHNOBEAT made substantial scientific progress along the defined aims and timelines. In particular, this includes the successful:
• modifications of bioreactor / components design and adaptation / systems integration of holographic monitoring technologies for hiPSCs cultured as cell aggregates in suspension
• derivation and characterisation of novel human induced pluripotent stem cell (hiPSC) lines by GMP-compatible protocols followed by cell distribution to partners
• improved methodology for the detection of genetic variants
• improvement of protocols for hiPSC expansion as well as cardiac and endothelial differentiation in suspension culture in stirred bioreactors and progression towards chemically defined GMP-compliant conditions
• formation of cardiac µ-tissues
• production of clinical grade human mesenchymal stem cells (MSCs) and distribution to partners
• establishment of cell aggregate/ µ-tissue transplantation in a pig model of myocardial infarction (MI)
All management and communication goals have been met as well.

Importantly, the project is marked by a great and highly supportive team spirit provided by all partners! This includes extensive exchange of students and scientists between all institutions, ensuring efficient transfer of know-how and technology as outlined in respective WP-specific parts of this report.

Final results

TECHNOBEAT’s contribution to achieving the expected impacts which range from:

• Short-term impact: development of improved bioreactor systems, cell monitoring and characterisation tools, large scale process for GMP-compliant stem cell -production, -differentiation, and µ-tissue engineering. These are all marketable tools, technologies, and cell-based products including µ-tissue based 3D assays of broad commercial value that will immediately strengthen Europe’s lead on biotechnology markets.

• Mid-term impact: will in particular include the robust proof of concept for the functional engraftment of transplanted hiPSC-progenies (applied as injectable µ-tissues) in physiological relevant preclinical models of myocardial infarctions. Moreover, the regulatory framework for hiPSC-based cell therapies will be shaped in close exchange with the national, European and global competent authorities as well as other stakeholders and networks thereby preparing the ground for the clinical translation of the hiPSC technology.

• Wider, long-term impact (TECHNOBEAT and beyond): will include the proof that hiPSC-based therapies can be safely applied to patients in clinical trials, can substantially support or even cure diseased hearts and thus help to overcome the shortage of donor organs. As a consequence, the approach might provide a substantial socio-economic benefit to the wellbeing of the aging European and global population.

Website & more info

More info: http://www.mh-hannover.de/technobeat.html.