End stage renal disease (ESRD) is an increasingly serious health issue that traditionally requires dialysis or renal transplantation. However, both options are associated with high morbidity and mortality, necessitating alternative solutions for the treatment of ESRD. The scope of the EU-funded NEPHROTOOLS (The potential of human kidney stem/progenitor cells for use in drug discovery and regenerative therapy programmes) project has provided novel treatment strategies for the treatment of ESRD. For drug- and cellular-based therapies, primary human renal cells and in vivo models are required. The NEPHROTOOLS consortium generated kidney stem progenitor cells (KSPCs) from various sources of human renal tissues and developed various models of mouse renal injury. Administration of KSPCs reduced fibrosis and integrated into the kidney underscoring the regenerative potential of these cells. In addition, researchers isolated KSPCs from preterm neonatal urine and found that they had long-term self-renewing capacity. A miniaturised electronic device that researchers developed for measuring the glomerular filtration rate (GFR) in awake mice significantly facilitated the monitoring of these parameters. With respect to drug testing, the consortium employed conditionally immortalised podocyte cell lines to establish a range of physiological and pharmacological assays. They also established in vitro protocols for inducing reproducible renal cell damage using the nephrotoxic drug, cisplatin. In another part of the project, scientists designed biomaterials capable of directing the differentiation of the KSPCs to specialised renal cells such as podocytes and proximal tubule cells. Among these materials were biodegradable hydrogels and porous membranes as well as biomimetic substrates that promoted cell differentiation. NEPHROTOOLS research activities demonstrated the preclinical regenerative potential of KSPCs offering a substantial alternative to standard interventions. By offering specialised training to a cohort of 15 researchers, the consortium has assisted the field of renal medicine and stem cell biotechnology.
Regenerative medicine, end stage renal disease, kidney stem progenitor cells, cisplatin, hydrogel