Project description
Stem cells from neonatal urine advance kidney cell therapy
Chronic kidney disease (CKD), caused by the loss of nephrons, claims 1.2 million lives annually. Renal cells are derived from sine oculis homeobox homolog 2 (SIX2)+ nephron progenitors, which are not present in the mature kidney. But kidney stem/progenitor cells (nKSPCs), which show high capacity to differentiate into functional kidney epithelial cells, were discovered in urine of neonates born before nephrogenesis was complete. The EU-funded NEOGRAFT project aims to establish nKSPCs as a novel source for preconditioning kidney allografts before transplantation. To this end, NEOGRAFT will elucidate the immunomodulatory profile of nKSPCs and their engraftment and regeneration potential at single-cell level, and will trace them in tissue using whole organ culture, ultimately aiming to directly immunomodulate and regenerate kidney tissue.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine transplantation
- medical and health sciences medical biotechnology cells technologies
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Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2021-COG
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1081 HV Amsterdam
Netherlands
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