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PROLIGEN Report Summary

Project ID: 36813
Country: Spain

Final Report Summary - PROLIGEN (Hypoxic Renal Proliferation)

Little is known about the temporal and spatial mechanisms that promote tissue healing after injury. A better understanding of this process would give rise to new diagnostic (perhaps even prognostic) approaches and indicate a basis for new treatment strategies, as there is a desperate need for market introduction of new drugs for this disease.

PROLIGEN sought to address this severe and debilitating societal problem for both patient and public health care by developing new strategies to understand, prevent and treat acute renal failure. PROLIGEN has achieved the information to foster kidney regeneration by providing knowledge on the gene control of mechanisms involved in regeneration.

In fact, we have obtained a list of genes and proteins that defines regeneration versus injury stage after ischemia/hypoxic insults. We have validated the genes in 'in vitro' systems using high throughput test systems to follow tubulogenesis and the change of macrophage phenotype. We have validated 14 genes and one protein in 'in vivo' models and delivered a new cell therapy using genetically modified macrophages to overexpress NGAL.

In this sense, the resulting gene function and the new cell therapy information has provided the PROLIGEN consortium with the necessary tools to deliver new biological and cell-based therapies for kidney regeneration.

This project differed from previous approaches in that the partners split the regeneration process into the different main biological process (apoptosis, formation of pro- versus anti-inflammatory mediators / macrophage phenotype and cell proliferation), and they aimed to study regeneration as the result of their interdependence. The consortium took into account that macrophages are at the centre of a complex regulatory network receiving and distributing signals from and to all biological process, thus affecting recovery.

At variance with previous studies, their particular focus was not only the identification of markers relevant for regeneration, but rather the use of functional genomic technology which provides a new network of gene function and new platforms to deliver a new cellular-based therapy strategy.

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