NEPHROTOOLS

The potential of human kidney stem/progenitor cells for use in drug discovery and regenerative therapy programmes

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 Obiettivo del progetto (Objective)

'Renal disease is a global public health problem, with the incidence of end stage renal disease (ESRD) rising annually. Current treatment options for ESRD are dialysis or renal transplantation, which have significant drawbacks in terms of increased morbidity and mortality, besides placing an increasing economic burden on society. The development of interventions aimed at preventing ESRD, including drug- and cellular-based therapies, is made difficult by the lack of availability of primary human renal cells for in vitro drug testing and by our inability to accurately assess the effectiveness of cellular-based therapies in appropriate animal models. However, due to recent advances in the fields of stem cell science, biomaterials and bioelectronics, we have unprecedented opportunities to generate the following tools that will facilitate important breakthroughs in renal medicine: (i) human kidney-derived stem/progenitor cells (KSPCs) for drug discovery and cellular therapy; (ii) biomaterials for regulating the differentiation of the KSPCs in vitro for use in drug development programmes; (iii) electronic devices capable of measuring renal function, enabling the effectiveness of stem cell-based therapies to be properly evaluated. The overarching goal of the NephroTools ITN is to provide state-of-the-art multidisciplinary training for a cohort of 15 young researchers in order to equip them with the skills required to make a significant impact in renal medicine and the wider field of stem cell biotechnology. To achieve this goal, the training of each researcher will be based around a specific research project, coupled with placement periods, within a multidisciplinary and cross-sectoral Network that aims to evaluate the potential of human kidney stem/progenitor cells for use in drug discovery and regenerative therapy programmes.'

Introduzione (Teaser)

Regenerative treatments are increasingly gaining ground as effective alternatives to tissue replacement approaches. Researchers are thus looking to identify and characterise cells capable of restoring organ function.

Descrizione progetto (Article)

Renal disease constitutes a major health problem worldwide. The only treatment options for end stage renal disease (ESRD) are renal transplantation, which suffers from donor shortages, and dialysis, which is associated with high morbidity and mortality. Efforts to develop new drug- and cellular-based therapies are hampered by the lack of availability of primary human renal cells for in vitro drug testing and lack of appropriate animal models.

Advances in stem cell science, biomaterials and bioelectronics have the potential to facilitate breakthroughs in renal medicine. . Research tools such as human kidney-derived stem/progenitor cells (KSPCs) and devices for measuring renal function should facilitate drug discovery and allow the evaluation of cellular therapy.

In this context, the EU-funded http://www.nephrotools.com/ (NEPHROTOOLS) project aims to develop such tools for use in renal medicine. For this purpose, they will generate and characterise KSPC lines and optimise their utilisation for drug discovery purposes.

So far, researchers have generated a number of KSPC lines, characterised their gene expression profile and are currently investigating their nephrogenic potential. To direct differentiation of KSPCs into specialised renal cells, a number of biomimetic substrates have been designed and synthesised. The consortium is also developing physiological and pharmacological assays for the utilisation of KSPC lines in drug discovery.

Ongoing work is directed towards evaluating the capacity of these cells to ameliorate disease in rodent models of kidney injury. For this purpose, researchers have developed a miniaturised electronic device for measuring the glomerular filtration rate in animals.

Collectively, the activities of the NEPHROTOOLS study will determine the clinical applicability of KSPCs in terms of therapy and drug discovery. At the same time, it will provide multidisciplinary training to the next generation of researchers in the field of renal medicine. Given the great need for novel therapies to prevent the development of ESRD, the overall project outcome is anticipated to have significant impact in the treatment of kidney disease.