STELLAR

Stem-cell based therapy for kidney repair

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 Obiettivo del progetto (Objective)

'Chronic kidney disease (CKD) affects 8% of the European population and ultimately results in renal failure due to progressive fibrosis. CDK carries a high mortality risk and the number of affected people rises, increasing the demand on renal replacement therapies while the number of available donor organs stays stable.

The STELLAR consortium proposes to develop an alternative to renal replacement therapy, based on the repair capacity of newly discovered kidney mesenchymal stromal cells (kMSCs). By injecting kMSC into affected kidneys, we expect to stop kidney fibrosis and induce tissue repair, ultimately leading to the restoration of normal kidney function.

The STELLAR consortium will • develop protocols for up scalable, high quality isolation of kMSCs and precisely characterize kMSC function in comparison to other MSCs. • test kMSCs in several murine renal disease models, to study their effects on fibrosis and tissue repair. • discover mechanisms of kidney repair. • invest in developing the technology necessary for up scaled isolation and quality control.

The STELLAR consortium combines Australian experts on kMSC isolation and characterisation with European experts on renal failure and compounds the state-of-the-art knowledge, facilities and experience needed to develop and validate this novel form of renal therapy. The inclusion of experienced SMEs, with great technical and scientific know-how about assay and protocol development, further strengthens the consortium and will ensure not only the inclusion of new technology, but also a quick translation from bench to clinical application.

In conclusion, the STELLAR consortium is capable of developing and pre clinical validation of this new cellular therapy for CDK, based on a new understanding of stromal cells and fibroblast function, while also providing the technology required for rapid, large scale application of the therapy after clinical validation.'

Introduzione (Teaser)

Mesenchymal stem cells (MSCs) are putative candidates for cell therapy in regenerative medicine. The STELLAR study is investigating a possible new role for MSCs in the restoration of kidney function.

Descrizione progetto (Article)

Nearly 8 % of Europeans will develop chronic kidney disease (CKD) and have a moderate to high risk that their kidneys will cease to function. Unless there is a suitable donor organ, CKD carries a high mortality risk and usually relies on kidney dialysis. However, the increasing disease prevalence and the shortage of available organs necessitate alternative solutions to renal replacement.

Based on the recent discovery that kidney mesenchymal stromal cells (kMSCs) possess inherent regenerative capacity, strategies that aim to restore the function of affected kidneys seem promising. With this in mind, scientists on the EU-funded project 'Stem-cell based therapy for kidney repair' (http://www.stellarproject.eu/ (STELLAR)) are investigating the effectiveness of kMSCs to stop organ fibrosis and induce tissue repair. In theory, this should lead to the restoration of normal kidney function.

By bringing together Australian and European experts in the field, STELLAR has developed protocols for the isolation of kMSCs and the characterisation of their properties. Compared to the well-characterised bone marrow or cord blood-derived MSCs, kMSCs have a similar phenotype.

However, kMSCs exhibit a higher potential for epithelial wound healing and vasculogenesis. Mechanistic insight into these properties has revealed homeobox-mediated transcriptional processes that could be involved in renal regenerative properties.

In the next phase of the project, partners will focus on the therapeutic impact of MSCs in specific disease models and on their large-scale expansion and differentiation. Among their objectives is also to understand the process of fibrosis and identify biomarkers for monitoring the effects of renal regeneration therapy using kMSCs.

Dissemination of the project activities through social media has emphasised the societal impact of STELLAR. Indeed, translating the fundamental knowledge obtained during the project into a clinical cell therapy product is expected to benefit renal disease sufferers throughout the world.