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How to regenerate the mammalian kidney

Project description

Mechanisms of regeneration of the kidney

Kidneys play a critical role in maintaining the body's internal balance, regulating blood pressure, producing important hormones, and filtering waste products. Unlike some animals, mammals and humans cannot regenerate their kidneys upon damage. Progressive damage and loss of kidney function may lead to chronic kidney disease, which is incurable, with the only treatment being lifelong hemodialysis. Funded by the European Research Council, the REGMAMKID project proposes to investigate the mechanisms of kidney regeneration in mice and to generate specific cell types for therapeutic purposes. By using these techniques, they will also model two genetic kidney disorders, which will greatly enhance our knowledge of kidney diseases and pave the way towards potential treatments.

Objective

Kidney non-endocrine functions are primarily performed by millions of individual integral units called nephrons. Although the adults of simple vertebrates (fish, amphibians and reptiles) have the ability to regenerate entire nephrons by a process called “nephron neogenesis”, this capacity is absent in birds and mammals. In this regard we have observed, for the first time, that the murine neonatal kidney is able to generate new nephrons after the resection of the 20 per cent of the kidney mass.
In the same manner, our recent published data on the generation of human kidney organoids ex vivo from kidney disease derived induced pluripotent stem cells (iPS), demonstrates the suitability of iPS technology to establish an unprecedented platform for drug screening, disease modelling and kidney regeneration.
Thus, with support from REGMAMKID we will carry out a dual strategy for kidney regeneration and therapy. For kidney regeneration, we will make use of our newly developed mouse model of neonatal kidney regeneration and identify the molecular and epigenetic drivers responsible for this process. For kidney therapy, we will generate specific kidney cell populations with therapeutic potential such as podocytes and tubular epithelial cells by combining emerging cutting-edge technologies from the fields of cellular reprogramming and pluripotent stem cells differentiation. Making use of the tools developed in REGMAMKID we will model two different genetic kidney disorders: one affecting the podocyte (Congenital Nephrotic Syndrome) and other leading to an excessive proliferation of tubular epithelial cells (Autosomal Dominant Polycistic Disease). These studies will significantly impact on our understanding of kidney disease and healing.

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2014-STG

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Host institution

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 604,00
Address
CARRER BALDIRI REIXAC PLANTA 2A 10-12
08028 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 604,00

Beneficiaries (1)

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