Welcome to STELLAR

STELLAR is an EU financed research consortium interested in developing an alternative to renal replacement therapy making use of newly discoverd kidney mesenchymal stem cells.

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Project

Project

STELLAR is a research consortium interested in developing an alternative for renal replacement therapy.
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Partners

Partners

STELLAR combines experts in the field of kidney development, regenerative medicine and kidney pathogenesis.
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Science

Science

STELLAR will make use of newly identified kidney stem cells to develop methods to fight chronic kidney disease.
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News

News

Any news on STELLAR meetings, publications and events can be found on our news blog or visit our Facebook page.
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STELLAR meeting IV King’s College London.

On November 24 and 25 the STELLAR consortium assembled at King’s College in London to discuss the progress of the project.

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The STELLAR project is active since November 2012. The first two years of this five year project has brought a wealth of knowledge on Mesenchymal Stromal Cells isolated from the kidney.

Our host Prof. Dazzi opened the meeting which started with a nice scientific program in which staff members of King’s and Imperial College presented work closely related to the STELLAR research topic.

The scientific session was followed by presentations of STELLAR’s junior research members showing the progress in the various work packages of the project.

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During the second day of the meeting the program for the coming 6 months was discussed. The meeting was concluded with a presentation of the health economics model specifically designed for the STELLAR project. The model, which was well appreciated by the STELLAR group members, can be used to predict the cost effectiveness of newly developed therapies that can delay the progression of kidney disease.

 

 

Public Event, the Personalized Kidney

Yesterday STELLAR’s coordinator, Ton Rabelink was invited to participate in a public event organised by the Radboud University Medical Centre.

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Topic of this public event was personalized kidneys, with an emphasis on what regenerative medicine could contribute towards alternatives for currently used renal replacement therapies in the near future.

The meeting was presented and moderated by  Astrid Joosten, a Dutch television celebrity. Over 200 patients and professionals attended the event.  Roos Masereeuw presented her work on a biological artificial kidney and Ton Rabelink presented the work currently performed within the STELLAR consortium.

Ton elaborated on the potential use of kidney derived Mesenchymal Stromal Cells to counteract fibrosis of the kidney.

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The evening was concluded with a lively interactive panel discussion. A number of controversial discussion topics were formulated to which the audience could agree or disagree by displaying a green or red card.

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A panel of experts gave their opinion on these statements which in some cases led to a change in opinion of the audience. The expert panel was a mix of Scientists, Nephrologists, an Ethical expert and the directors of the Dutch Kidney Foundation and the Dutch Kidney Patient Organisation.

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Below some of the statements discussed:

  • Personalized kidneys means that the best quality donor organs (those from young donors) should be used for young patients. Old patients should be given kidneys of lesser quality.
  • The patient should take responsibility for its own health. The introduction of a scoring system to select for kidney organ recipients based on the patient’s lifestyle can be justified.
  • Someone registered as an organ donor should get priority when needing a donor organ over those not registered as organ donors.
  • Expensive treatments such as dialysis and transplantation can in part be avoided through a healthier lifestyle. The government should place restrictions on the amount of salt allowed in food articles.

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ISSCR Webcast by Melissa Little on Growing a Kidney in a Dish

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Stem Cells in Focus is an ISSCR topic in which a series of webcasts is organized allowing the public to discuss Stem Cell topics with leaders in the field.

Yesterday STELLAR member Melissa Little dicussed her topic during a webcast session on: Exploring Organoids: Growing a Kidney in a Dish.

Below is an interview with Melissa conducted by Maya Chaddah leading up to the webcast.

Melissa Little

There was great excitement in 2013 when Australian scientist, Prof. Melissa Little, at The University of Queensland’s Institute for Molecular Bioscience in Brisbane, Australia saw tiny buds of tissue growing in a dish that looked like embryonic kidneys. Originally a cancer geneticist, she had spent years studying the genes and pathways that lead to the formation of Wilm’s tumor, a kidney cancer found in children. As the connections between abnormal kidney formation during development and kidney dysfunction in children became apparent, she began exploring new ways to help individuals with kidney disease.

In the 15 years since Prof. Little started focusing on kidney development, renal disease and repair, the rates of chronic kidney disease have skyrocketed globally, due in large part to conditions like diabetes, hypertension (high blood pressure), glomerulonephritis (immune-mediated disease) and cardiovascular disease. Although the adult kidney can repair some damage – for example, after a night of excessive alcohol, a period of dehydration, rapid blood loss, or exposure to chronic toxins – it cannot grow new nephrons, which are vital to its function, after we are born. So chronic kidney damage takes its toll and ultimately leaves individuals on dialysis or awaiting kidney transplants, which are in very short supply.

The kidney is a very complex organ, comprised of 250,000 to 2 million nephrons that filter the blood (about 5 cups/minute), resorb nutrients and excrete waste. Each nephron is shaped like the head of a wrench leading into a long convoluted tube that bends and winds. Blood is filtered at the head of the wrench and different points along the tube take back what the body needs – ions, amino acids and water. The tube then dumps what the body doesn’t want into a large pipe called the ‘collecting duct,’ which funnels the waste to the bladder for excretion. Any condition that repeatedly affects the ability of the nephrons to filter the blood can lead to a build-up of kidney damage over time.

Prof. Little’s team was keen to understand kidney development in humans. Because the adult human kidney cannot make new nephrons, they attempted to replicate the process by which nephrons develop in the human embryo, using cultured cells grown in the laboratory. This involved identifying the conditions under which embryonic stem cells – derived from the earliest unspecialized cells in an embryo – can be coaxed to make mesoderm, the layer of cells in the early embryo with the potential to make kidney cells. From there, they developed a very tight, quality controlled method for reproducibly making nephron progenitors, the cells which make nephrons, as well as early nephrons and collecting duct cells.

What Prof. Little’s team finds amazing is how exactly these types of cells, the nephrons and their progenitors and collecting duct cells, self-assemble into three dimensional structures outside the body, in a totally artificial lab environment. She likens the mystery to when animals are born and immediately just know how to stand up and go to their mothers. The kidney organoids her team can grow right now are only tiny buds of tissue, much smaller than normal kidneys and less complicated, but clearly with the same kinds of cells found in an embryo making a kidney. The next steps are to keep pushing the kidney organoids down the developmental pathway that ends with fully functional organs, and then to investigate whether the nephrons could do their job if given a blood supply.

Prof. Little sees a few ways that functional kidney organoids could open new avenues of discovery in the near future:

  1. Kidney organoids are made with human cells, so they mimic early human kidney development more closely than mouse models, allowing researchers to better study the organ and its diseases
  2. Kidney organoids promise a more patient-specific way to model what goes wrong in disease. If researchers are able to accurately and quickly replicate the types of mutations found in particular patients, they can better treat them (eventually leading to more directed treatments)
  3. Kidney organoids could become test beds for assessing whether experimental drugs are toxic to the kidney – lack of adequate testing models is one of the main reasons that drug development fails and incurs such enormous costs

Because the kidney is such a large, complex organ, it is unlikely that scientists will be able to grow life-sized kidneys for the purpose of transplantation. But in the distant future, even tiny kidney organoids might provide enough functional filtration to benefit patients. There is still a long, long way to go, but just being able to make kidneys organoids is bringing scientists like Melissa Little one step closer to helping people with chronic kidney disease.

STELLAR at the 5th MISOT meeting

The Fifth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Bergamo on March 20 and 21, 2014.

The majority of the STELLAR members were present and actively contributed to the symposium either as speakers, and/or chairperson to one or more of the sessions.

The ageing population and the increase in people suffering from diabetes and hypertension have led to an ever increasing demand for kidney donor organs. The search for new methods to circumvent the use of scarce donor organs is a priority for researchers in the field. In the STELLAR project research focuses on the novel concept that the interaction of interstitial stromal cells with the local immune system may regulate tissue homeostasis and the balance between tissue repair and fibrosis. MSC residing in the kidney may enhance the intrinsic reparative capabilities of the kidney. In STELLAR the potential use of these kidney MSC for the treatment of patients with kidney disease is investigated.

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Ton Rabelink, the coordinator of the STELLAR consortium, discussed the intrinsic reparative capabilities of kidney derived Mesenchymal Stromal Cells (MSC) thereby showing  the latest results from the STELLAR project.

Martino Introna, in STELLAR responsible for the production of MSC derived from umbilical cord, elaborated on the hurdles that need to be taken when running a GMP production facility in a public hospital context for the expansion of MSC. His MSC have so far been used in a number of phase I/II clinical trials focusing on patients suffering from Graft versus Host Disease after hematopoietic stem cell transplantation, for the reduction of immunosuppressive therapy in renal failure patients undergoing kidney transplants and for the therapy of Multiple Sclerosis patients.

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Marlies Reinders, STELLAR member and clinician showed results from a clinical trial in which patients receive MSC after the first signs of possible kidney rejection following kidney transplantation. She also presented a new study that will be started at the Leiden University Medical Centre which will test the hypothesis that MSC will facilitate the reduction of immunosuppression, reduce fibrosis and decrease the incidence of opportunistic infections in patients receiving a kidney transplant.

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Giuseppe Remuzzi, the host of the STELLAR and MISOT meetings briefly discussed his results obtained when treating kidney transplant patients with MSC. To gain more insight in the clinical observations of his team they investigated the mechanisms of MSC infusion in a murine kidney transplant model. Results from these preclinical studies indicate that pre-kidney transplant infusion of MSC induced a prolonged survival of the kidney graft.

Question on when to administer MSC: pre- or post-transplantation, what MSC to use: allogeneic or autologous, derived from which tissue source and whether they should be fresh or frozen were discussed during the meeting. The need for a more standardized clinical protocol was discussed. These topics will be on the agenda for the next MISOT meeting that will be hosted by STELLAR coordinator Ton Rabelink in the Netherlands.

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STELLAR meeting III

Last week the STELLAR consortium teamed up to discuss the progress on the project.

STELLAR meeting III was hosted by the Mario Negri institute in the beautiful Villa Camozzi in Bergamo, Italy.

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Our host Prof. Remuzzi opened the meeting with a warm welcome and a presentation of the latest results from his group.

STELLAR meeting III was very efficient and fruitful. With the first reporting period coming up soon Prof. Rabelink discussed all deliverables that are due in the first two years. The team is right on track. New plans for the coming 6 months were made.

The meeting was concluded with a nice dinner at which discussions on the project continued.

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An overview of the STELLAR contribution to the ISN forefronts symposium on Stem Cells and Kidney Regeneration.

Experts from around the globe assembled in Florence for the ISN Forefronts Symposium on Stem cells and kidney regeneration. During this 4 day symposium various aspects of stem cells and their use for kidney regeneration were presented and discussed .

The majority of the STELLAR members were present and actively contributed to the symposium either as speakers, poster presenters and/or chairperson to one or more of the sessions.

On Thursday September 12 posters were displayed by a number of STELLAR members: Danielle Leuning, Joan Li and Martina Aleksinskaya. The posters discussed the following topics: “Characterization of human kidney derived mesenchymal stromal cells”, “Epithelial origin and specific differentiation potential of endogenous renal MSC-like cells” and “Chronic kidney disease is associated with hematopoietic stem cell niche dysfunction”.

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On Friday September 13 Melissa Little presented her work on transcription factor driven reprogramming of various cell types to the nephron progenitor population. This type of cells gives rise to all daughter cells forming the nephrons, the building blocks of the kidney crucial for healthy kidney function.

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Three of the five poster abstracts selected for oral presentation were provided by researchers affiliated to the STELLAR consortium.

  • Roel Bijkerk discussed his work on the protective effect of MIR-126 against renal ischemia reperfusion injury through the promotion of vascular integrity.
  • Joan Li discussed her work on endogenous MSC like cells from the kidney, showing that they have the potential to integrate into the neonatal collecting duct via mesenchymal-to-epithelial transition. If these cells play a role in normal tissue turnover they might be useful in the treatment of renal damage.
  • Elena Lazzari discussed her work on the isolation and characterization of urine-derived renal progenitors from pediatric patients affected by glomerular diseases. These cells which can be readily obtained might provide a useful tool to study underlying genetic causes of renal disease.

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Friday evening was concluded with an informal STELLAR training. All junior STELLAR members assembled over dinner for a discussion on science and the STELLAR project with board members Ton Rabelink, Joost de Bruijn and Melissa Little. This get together allowed the STELLAR team to get to know each other and strengthen collaborations for the coming years of the project. STELLAR was fortunate enough to be able to invite Benjamin Humphreys to the training session. He is the director of the Harvard Stem Cell Institute Kidney Program and one of the main players in the field of regenerative medicine approaches for kidney regeneration.

On September 14 Paola Ramagnani one of the organizers of the meeting and STELLAR member, presented her work on renal progenitors and kidney regeneration. STELLAR member and president of the ISN, Guiseppe Remuzzi discussed one of the many topics he is working on in the field. The audience was treated to a beautiful presentation of the results from clinical studies using mesenchymal stem cells to counter unfavorable immune responses that occur during kidney transplantation.

 

September 15, the last day of the symposium was filled with excellent presentations. One of which was presented by STELLAR coordinator Ton Rabelink. He discussed the importance of stem cells in the bone marrow niche with respect to vascular repair in kidney damage and regeneration.

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The STELLAR consortium is looking back on an excellent symposium which was very well organized with world class speakers, fruitful discussions and rewarding interactions.

We would like to thank the organizers Benjamin Humphreys and Paolo Romagnani for putting together such an amazing program.

 

ISN Forefronts symposia Florence

STELLAR will be present at the ISN Forefronts symposia which will be held in Florence, Italy from 12-15 September 2013.

STELLAR will organise a STELLAR training session for the junior members of the consortium.

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STELLAR meeting II

STELLAR meeting II will be organised by LUMC.

Date: 1-2 July 2013

Place: Oud Poelgeest, Oegstgeest (close to Leiden)

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