Project description
Development of stem cell-based cardiomyocytes manufacturing for heart failure repair
Human leukocyte antigen (HLA) proteins are expressed on the cell surface, enabling the immune system recognition of foreign cells. Cells from HLA-homozygous donors can be used for therapies in patients with at least one of the same HLA type. The EU-funded HEAL project aims to advance the HLA homozygous stem cell-derived cardiomyocyte technology for restorative therapy in heart failure with minimal immunosuppression. The objectives include the development of an artificial intelligence algorithm to predict individual immune responses, optimisation of cell product administration, and risk assessment of graft-induced arrhythmia in an animal model. The goal is to obtain approval for the products and related assays and protocols to progress towards the first-in-man study of cell-based heart failure repair.
Objective
HEAL will focus on general bottlenecks to induced pluripotent stem cell therapies with a particular focus on heart failure, which remains a major cause of morbidity and mortality with very few treatment options.
HLA-homozygous cell line derived cardiomyocyte aggregates offer the prospect of a restorative heart therapy applicable to large patient populations and to overcome economic barriers associated with autologous approaches. By developing solutions for their mass-production and cryopreservation we will enable allogeneic treatment with minimum requirements for immunosuppression.
Assays for assessment of immunogenicity will provide data for the development of an artificial intelligence powered algorithm to predict recipients's immune responses for personalised design of immunosuppression protocols.
A potency assay to assure product effectiveness will be developed together with assays of tumorigenicity in vitro and in vivo that meet and exceed current regulatory requirements. A genetic integrity pipeline defining the most sensitive assays for rigorous assessment will be developed and a rescue tool in the form of a biallelic suicide gene for programmed cell death will add to the safety toolbox for the therapy.
Optimisation of cell-product administration in terms of retention and engraftment, including catheter-based delivery as minimally invasive alternative to surgical application, and assessment of risks of graft-induced arrhythmia will be determined in a pig model.
Early dialogues, via established links, to the regulatory authorities will ensure proper development according to GMP requirements.
Freedom to operate and licensing strategies with a health technology and infrastructure assessment of European centres will set the scene for approval of the cell product and related assays and protocols for storage and distribution required to progress towards a first in man study of cell-based heart repair.
Fields of science
- natural sciencescomputer and information sciencesartificial intelligence
- medical and health sciencesclinical medicinecardiologycardiovascular diseasescardiac arrhythmia
- social sciencessociologydemographymortality
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Keywords
Programme(s)
Funding Scheme
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinator
30625 Hannover
Germany