Ricerca Progetti nazionali, regionali, internazionaliNAZIONALIPRIN 2022Sensing kidney damage

Sensing kidney damage and tumor trasformation piezoelectric nanowebs

Kidney diseases are a major global health burden. Acute kidney injury (AKI) affects one in five people admitted to hospital emergency departments and the global prevalence of chronic kidney disease (CKD) is >10%, with high morbidity, mortality, social impact, and costs. Kidney damage can not only cause CKD, but also renal cell carcinoma (RCC). Renal progenitors (RPC), the cells driving tissue repair in response to kidney damage, link damage and RCC, being the cell of origin of different subtypes of RCC. Clinically, kidney damage isfrequently recognized late because sensitive markers are lacking. For this reason, discovery of drug nephrotoxicity often occurs only after market implementation. This project aims to address two important unmet medical needs by using an innovative strategy to: 1. to set up a method for preclinical screening of drug nephrotoxicity, and 2. to establish an innovative tool that distinguishes healthy kidney cells from neoplastic cells. To address these major unmet medical needs, we plan to establish an unconventional approach, i.e., a multifunctional nanostructured glomerulus (Bio-GLOM) and tubule (Bio-TUBE) designed to reproduce the "morphology", "architecture" and "function" of the natural organ compartments using RPC differentiated into podocytes or tubular cells or transformed by NICD1 transfection, grown on 3D-shaped piezoelectric nanowebs. These organs will then be internally interrogated in terms of phonetic speech. Indeed, the occurrence of damage leads to sudden changes in the material as "impulsive" energy releases, inducing local vibrations that become an acoustic source. The produced acoustic signals carry the fingerprints of the source. We will establish a database of main fingerprints of kidney damage inferred from the main nephrotoxic agents, that will act as referral for potential nephrotoxicity of a new drug when it is still in a preclinical phase. Such a method would have two major impacts: 1. Reducing the costs of compound screening; 2. Reducing the harm of drug nephrotoxicity, with possible economic and social implications. The second important aim of this project will be to optimize the same strategy to investigate the initial phase of transformation of healthy into neoplastic kidney cells. Our innovative strategy may indeed permit to identify fingerprints that distinguish healthy kidney cells from neoplastic ones and that may be used to establish novel methods for liquid biopsy, with patentability and potential social impact. To reach these ambitious aims, we joined leading expertise in the domains of kidney regenerative medicine and of advanced materials. Altogether, we predict that this project will lead to set-up of new tools for screening of potential toxicity of new drugs and to identify fingerprints of RPC transformation for optimization of liquid biopsy and early diagnosis of RCC.

 

 

Data di avvio 18 Ottobre 2023

Data di completamento 18 Ottobre 2025

Total cost  €119718,00

 

Progetto 20223K88HY finanziato all’interno del Bando PRIN 2022 di cui al Decreto Direttoriale n. 104 del 02/02/2022 nell’ambito del Piano Nazionale di Ripresa e Resilienza, Missione 4 – Componente 2. Dalla Ricerca all’Impresa - Investimento 1.1 Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN), finanziato dall’Unione europea – NextGenerationEU – CUP B53D23021060006