Description du projet
Les cellules souches issues de l’urine des nouveau-nés font progresser la thérapie cellulaire rénale
L’insuffisance rénale chronique (IRC), causée par la perte de néphrons, fait 1,2 million de victimes chaque année. Les cellules rénales sont dérivées des progéniteurs du néphron sine oculis homeobox homolog 2 (SIX2)+, qui ne sont pas présents dans le rein mature. Mais des cellules souches/progénitrices du rein (nKSPC), qui présentent une forte capacité à se différencier en cellules épithéliales rénales fonctionnelles, ont été découvertes dans l’urine de nouveau-nés avant que la néphrogenèse ne soit achevée. Le projet NEOGRAFT, financé par l’UE, entend établir les nKSPC en tant que nouvelle source pour le préconditionnement des allogreffes rénales avant la transplantation. À cette fin, NEOGRAFT fera la lumière sur le profil immunomodulateur des nKSPC et leur potentiel de prise de greffe et de régénération au niveau de la cellule unique, et les suivra dans les tissus en recourant à la culture d’organes entiers, dans le but ultime d’immunomoduler et de régénérer directement les tissus rénaux.
Objectif
Global mortality from chronic kidney disease (CKD) is estimated at more than 1.2 million annually. CKD is caused by the irreversible loss of nephrons, the structural and functional units of the kidney. Lineage tracing revealed that all renal cells are derived from a SIX2+ embryonic progenitor population originating at the cap mesenchyme (CM). SIX2 is essential for cells’ self-renewal, and its cessation signals the initiation of nephron differentiation. However, SIX2+ progenitor cells are exhausted in the mature kidney.
My team has recently discovered a novel unique source of kidney stem/progenitor cells (nKSPCs) derived from the urine of neonates born before the completion of nephrogenesis. nKSPCs express SIX2 as well as various other CM progenitor markers, and they show a high capacity to differentiate into functional kidney epithelial cells. Additionally, our data show that nKSPCs have an immunomodulatory capacity in vitro. Using normothermic machine perfusion (NMP) of human kidneys, we have discovered that nKSPCs are able to reduce inflammatory responses and activate regenerative processes.
Building on these findings, I aim to establish nKSPCs as a potent novel cell type for the development of kidney-targeted cell therapy for preconditioning kidney allografts prior to transplantation. To this end, I will elucidate the immunomodulatory profile of nKSPCs and demonstrate their potential for engraftment and regeneration at single cell level using advanced methodologies for the first time in this field. Moreover, I will use the ground-breaking pre-clinical platform of whole organ culture system to trace single nKSPCs in kidney tissue over a longer period of time after injection.
nKSPCs are an unexplored progenitor cell type, which might revolutionize the field of kidney diseases.
My long-term goal is to establish clinical-grade nKSPCs for the development of kidney-targeted cell therapy with the capacity to directly immunomodulate and regenerate kidney tissue.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
1081 HV Amsterdam
Pays-Bas