Project Portugal 2030

Summary

The RenalRevive project endeavors to address critical challenges in renal disease treatment and advance the state of the art in regenerative medicine. The primary objective is to develop an innovative therapy targeting the early stages of renal diseases, where existing treatments are limited, and the risk of progression to irreversible conditions is high. The injectable decellularized kidney extracellular matrix (DKECM) hydrogel will deliver renal reparative cells and endothelial cells’ extracellular vesicles (EVs) into the kidney enabling maximal cell engraftment and promoting kidney remodeling and regeneration. The proposed research tackles the challenge of the inadequacy of current treatments for chronic kidney disease (CKD). Despite the high morbidity associated with renal diseases our current treatment relies only in extrinsic renal function replacement. RenalRevive seeks to disrupt this paradigm by targeting the initial phases of renal dysfunction, preventing the progression to irreversible stages, and ultimately radically improving patient outcomes. The objectives of the project extend beyond the state of the art by introducing novel concepts and approaches in tissue engineering and regenerative medicine. The use of DKECM as a basis for the development of injectable hydrogels, combined with specific renal reparative cells and endothelial cells’ EVs, represents a unique and innovative strategy. This approach leverages the inherent regenerative potential of the extracellular matrix while maximizing the cellular engraftment and paracrine signaling to enhance therapeutic efficacy. Moreover, the collaboration with nephrologists and veterinary specialists and the development of a transitional AKI-to-CKD animal model contribute to the project's ambitious vision. RenalRevive aims to create a realistic and representative animal model of the transition from acute to chronic kidney disease, allowing for a detailed evaluation of the safety and therapeutic efficacy of the advanced therapy. This is particularly significant because the prevailing animal model of CKD) involves a 5/6 nephrectomy, resulting in a substantial reduction in renal functional mass. This procedure mimics the advanced stages of kidney disease, where the chances of reverting the fibrosis are very low. In summary, RenalRevive addresses crucial challenges in kidney disease treatment by targeting early stages, and proposes ambitious objectives that surpass the current state of the art. This multidisciplinary approach, involving experts in veterinary sciences, surgery, and regenerative medicine, enhances the project's ambition and potential for groundbreaking advancements. The integration of novel concepts and interdisciplinary collaboration positions this project as a pioneering initiative with the potential to revolutionize the field of regenerative medicine and offer transformative solutions for patients suffering from renal diseases.