Concept and Aims
Cardiovascular diseases, including myocardial infarction (MI), are the leading cause of pre-mature death worldwide, constituting a major socio-economic burden on the European and global healthcare. At present, whole organ transplantation is still the ultimate treatment option for end-stage heart failure patients in the wake of MI. But heart transplantation is limited by organ availability and requires life-long administration of immunosuppressive drugs. Therefore, MI patients would particularly benefit from advanced cell therapies aiming at the functional reconstitution of damaged heart tissue by the administration of heart muscle cells, thereby avoiding organ failure.
Human induced pluripotent stem cells (hiPSCs) can be derived from patients’ own somatic cells by a recently developed technology termed “Reprogramming of Mature Cells”. This ground-braking technology was recently developed by the Japanese researcher Shinya Yamanaka, who was awarded the Nobel Price for this achievement in 2012 (https://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/yamanaka-facts.html).
In contrast to somatic cells and adult stem cells ( which can be harvested from blood, bone marrow or other human tissue), hiPSCs have an unlimited expandability and can be differentiated into essentially all somatic cell types, including cells constituting the heart such as cardiomyocytes, endothelial cells, pericytes and connective tissue-forming cells. These features make hiPSCs highly attractive as a universal cell source for organ repair. However, technologies for the robust production of hiPSC-derived progenies in therapeutically mandatory scale and in line with regulatory compliant Good Manufacturing Practice (GMP)-standards at reasonable cost, are currently lacking.
These limitations define the key objectives of the project.
1) Advance 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.
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 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.