AXHELERATE

Cardiovascular disease is the leading cause of morbidity and mortality worldwide with the global annual healthcare costs projected to exceed $1 trillion by 2030. This enormous health and socioeconomic problem cannot be tackled unless novel cardiac regenerative medicine therapies, are realized. Accordingly, AXHELERATE investigates a novel, developmental mechanism involving the genesis of new heart muscle from axial progenitor cells during fetal heart morphogenesis. Traditionally, axial progenitors contribute to the development and elongation of the lower body axial muscles and neurons, but their role in the heart remains elusive. Addressing this question may unlock new therapeutic avenues, because understanding the developmental mechanisms that produce the final shape and size of the human heart, would lead to their pharmacologic or genetic stimulation to drive regeneration in response to heart disease. AXHELERATE is an interdisciplinary team of developmental biologists, electrical, mechanical, and software engineers, dedicated to solve this question within 24 months, through a well-defined approach that has 3 aims: Aim 1 employs (a), novel pluripotent stem cell-derived organoids as in vitro models of axial and cardiac progenitor cell development; and (b), in vivo mouse models of neonatal heart regeneration; to fate-map the role of axial progenitors in the developing and regenerating heart, respectively. Aim 2 constructs a novel IoT-based organoid bioreactor with metabolite monitoring capabilities to optimize the organoid models of human development and regeneration. Whereas, Aim 3 tests a novel metabolic mechanism as a potential therapeutic target for controlling the developmental and regenerative capacity of axial progenitor-derived cardiomyocytes. AXHELERATE’s team is supported by 3 additional groups of experts, ensuring the successful and timely completion of this high-risk/high-gain project.

Consortium

ARISTOTLE UNIVERSITY OF THESSALONIKI (AUTH), Greece
ETHNIKO KENTRO EREVNAS KAI TECHNOLOGIKIS ANAPTYXIS (CERTH), Greece