Project Portugal 2030

Summary

Obesity is a known risk factor for cardiovascular disease, musculoskeletal and osteoarticular disorders, and peripheral neuropathies. Growing evidence suggests that these diseases are increasingly associated with the systemic effects of adipose tissue dysfunction, driven in part by the excessive release of adipokines, fibrotic inductive factors, inflammatory cytokines, and lipids. The multifaceted origins and intricate physiological impacts of obesity require comprehensive research to fully comprehend the condition, which is essential for developing innovative treatment and prevention strategies. The majority of obesity centered research has focused primarily on animal models and two-dimensional cell cultures, which face significant limitations. These include interspecies variability, insufficient accuracy in predicting human outcomes, and the inability to replicate the 3D microenvironment of human tissues. Consequently, there is an increasing demand for more sophisticated microphysiological systems that can accurately reproduce human adipose tissues. To address these challenges, this biotechnology project will leverage a multi-cell organ-on-chip platform integrating human adipose tissue, neurons, cardiomyocytes, tenocytes, and muscle cells to study the systemic effects of obesity and assess therapeutic interventions. By simulating human pathologic conditions at a micro-scale, this approach aims to provide a novel platform for studying and treating obesity-related tissue injuries, ultimately enhancing recovery and improving patient outcomes after successful weight loss interventions. Specifically, Organ-OB main objectives include: i) establishing cell sources for multi-tissue modeling of human disease; ii) engineering a functional Organ-on-Chip system; and iii) deciphering multi-organ cellular and molecular responses to obesity. These experimental activities will be integrated with coordinated project management and results translation strategies to ensure the scientific and societal success of the project. Organ-OB brings together a multidisciplinary team of 15 members from UMIB, 2 members from CIAFEL, and 3 members from UnIC, combining expertise in metabolism, cardiac and muscle function, neurobiology, bioengineering, and iPSC-based disease modeling. This synergy is essential to the ambitious research program outlined in this proposal. This project represents a crucial step towards addressing the unmet needs of tissue regeneration and weight loss for an integrative and comprehensive approach to obesity treatment, rendering it even more relevant from the physician, patient, and societal perspective.