Descrizione del progetto
Come rispondono i reni alle lesioni?
L’identificazione di cellule staminali/progenitrici endogene in vari organi ha contribuito a una più profonda comprensione dei meccanismi delle malattie e alla scoperta di nuovi approcci terapeutici. Evidenze recenti indicano che i progenitori renali sono coinvolti nelle patologie renali, le quali rappresentano un problema di salute a livello globale. Il progetto RENOIR, finanziato dall’UE, intende studiare il ruolo di tali progenitori nelle lesioni renali e nel carcinoma a cellule renali. Inoltre, i ricercatori seguiranno lo sviluppo dei progenitori renali dallo stadio embrionale a quello adulto e ne studieranno la nicchia durante la crescita, l’omeostasi e l’invecchiamento dei reni. In definitiva, li esamineranno come bersaglio terapeutico per la rigenerazione dei reni e la regressione delle malattie. La coltura dei progenitori renali a partire dall’urina offre la possibilità di un approccio terapeutico personalizzato.
Obiettivo
Kidney disorders represent a major global health issue and new tools are needed to expand disease modeling and therapeutic options. The identification of renal progenitors (RPC) opens a wide range of possibilities to support progress in several fields of nephrology. Indeed, RPC have become a key player in the pathogenesis of kidney disorders, and their study is increasing knowledge about the mechanisms of kidney response to injury. In this project we propose new lineage tracing models to identify and characterize mouse RPC system. We then will use these models to establish RPC role in progression or resolution of glomerular and tubular injury, and the mechanisms involved in these processes. Furthermore, the role of abnormal RPC function in the pathogenesis of renal cell carcinoma will be established. We will proceed to validate RPC as therapeutic targets to improve podocyte regeneration and disease regression. Lineage tracing of the murine RPC system from development to adult life and characterization of the RPC niche will be performed through observation of RPC at various stages of nephron formation during development as well as during kidney growth, homeostasis and aging. RPC isolation and culture from kidney tissue being limited due to their inaccessibility, the recent development of a method for culturing them specifically from urine finally opens the perspective of personalized medicine of the kidney and the development of patient-specific treatment strategies. In addition, patient-specific RPC can be useful for screening of new drug compounds, developing disease-modifying assays, as well as for evaluation of drug toxicity, with particular regard to nephrotoxicity. Finally, RPC represent potential tools and/or targets for therapeutic purposes and to promote innovative renal replacement strategies for kidney disorders.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
50121 Florence
Italia