Descripción del proyecto
Células madre de la orina neonatal mejoran el tratamiento de las células renales
La insuficiencia renal crónica (IRC), causada por la pérdida de nefronas, se cobra 1,2 millones de vida cada año. Las células renales se derivan de las células progenitoras de nefronas del homeodominio homólogo 2 (SIX2)+ del seno oculto, que no están presentes en el riñón maduro. Sin embargo, se han descubierto células madre o progenitoras renales (nKSPC, por sus siglas en inglés), que muestran una alta capacidad para diferenciarse en células renales epiteliales funcionales, en la orina de los neonatos nacidos antes de la finalización de la nefrogénesis. El proyecto NEOGRAFT, financiado con fondos europeos, aspira a establecer las nKSPC como una nueva fuente para el acondicionamiento previo de aloinjertos renales antes del trasplante. Para este fin, NEOGRAFT dilucidará el perfil inmunomodulador de las nKSPC y su potencial de injerto y regeneración a nivel de unicelular, y realizará su seguimiento en el tejido utilizando un cultivo de órgano completo, con el objetivo final de inmunomodular y regenerar directamente el tejido renal.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
1081 HV Amsterdam
Países Bajos