Descripción del proyecto
Desarrollo de la producción de cardiomiocitos derivados de células madre para la corrección de la insuficiencia cardíaca
Los antígenos leucocitarios humanos (ALH) son proteínas que se expresan en la superficie celular que permiten al sistema inmunitario reconocer células extrañas. Las células de donantes con ALH homocigóticos se pueden emplear para tratar pacientes con al menos un mismo tipo de ALH. El equipo del proyecto HEAL, financiado con fondos europeos, se propone mejorar la tecnología para producir cardiomiocitos derivados de células madre homocigóticas para ALH para el tratamiento corrector de la insuficiencia cardíaca con una inmunosupresión mínima. Sus objetivos incluyen el desarrollo de un algoritmo de inteligencia artificial para predecir respuestas inmunitarias individuales, la optimización de la administración de productos celulares y la evaluación del riesgo de arritmia inducida por injerto en un modelo animal. La finalidad es obtener la autorización de los productos, así como de los ensayos y los protocolos relacionados, para avanzar hacia el primer estudio en seres humanos de la corrección de la insuficiencia cardíaca con células.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinador
30625 Hannover
Alemania