Could lab-grown mini-kidneys change patients’ lives?

Several labs in Europe are growing mini-kidneys to be used for disease modelling, in the hope that in the future, they can be used as transplants for those in need. 

In Europe, chronic kidney disease (CKD) affects about one in ten citizens. It increases the risk of heart attack and stroke, and in some cases, can progress to kidney failure – requiring dialysis or transplantation.

This “alarmingly high number is expected to grow even further, as typical risk factors such as diabetes and hypertension become more prevalent,” Health Commissioner Stella Kyriakides told EU lawmakers during a plenary debate on a systematic EU approach to CKD in March.

Jitske Jansen, a scientist in Kramann Laboratory at the university hospital in Aachen, Germany, has been working on the creation of lab-grown mini-kidneys. The aim is that these mini-kidneys can be used for disease modelling, potentially revealing insights that can be used to create more effective drugs for the around 600 million people worldwide living with some form of kidney damage. 

Ultimately, the hope is that research groups will be able to grow an entire adult kidney in a lab that could be used for transplantation. Jansen estimated that this could happen 15-20 years from now.

Organ shortage is a big challenge for Europe: on average, an estimated 18 patients die each day while on the waiting list for a transplant.

EU initiative on chronic illnesses may ‘indirectly’ help kidney patients, Commission says

Although not included in the EU’s list of major non-communicable diseases, chronic kidney disease (CKD) will benefit from an ‘indirect’ impact of the work on other conditions that share common risk factors, according to the European Commission.

How to grow a mini-kidney

Jansen explained that the process starts with human skin fibroblast or blood cells. By using proteins involved in the process of transcribing DNA into RNA, known as transcription factors, the fibroblast or blood cells are turned into artificial stem cells – known as induced pluripotent stem cells (iPSCs).

“With these [iPSCs], you can grow into any kind of tissue you’re interested in – in our case, kidneys, as we are kidney researchers,” she told EURACTIV.

“It’s important that the timing is correct, as well as the concentrations to make sure that you differentiate towards kidney because, if you don’t use the correct factors or signalling or pathway activation, you end up with an entirely different organ,” she added.

After a week, cells are detached and turned into 3D structures that have nephrons, blood filtering tubes, and the consistency of a kidney.

This whole process is set to mimic nephrogenesis, a kidney development that happens during gestation in the mother’s womb. In this case, it happens in a lab and the organoids seen are not fully mature yet as there are cells that are still “iPSC-like”. 

“[It] is not the Holy Grail yet,” Jansen said, but the results are moving closer to resembling an adult kidney.

The technology first emerged in the pages of scientific journals seven years ago. Since then, however, iPSC-derived organoids technology has raced forward.

“If you have a kidney patient, and we get cells from the patient, either fibroblasts or blood cells, we make iPSC cells, and we make a mini-kidney in the lab, and at a certain stage, we could perhaps transplant it into the patient,” Jansen said.

Disease modelling

To better understand kidney disease mechanisms, such as kidney fibrosis, labs are adding pathogenic circulating factors to the organoids to attack the kidney cells.

Jansen said she hopes that the observation of this process will enable scientists to better answer questions such as why the kidney cell is affected, what is happening in the cell, and ultimately: how we can prevent it.

Currently under the microscope is prednisone, a commonly used drug for certain kidney disorders or after kidney transplantation.

“The doctors have no clue how this prednisone actually really works. Some patients recover and go into remission, and other patients get prednisone and will not go in remission, meaning that the disease remains active,” she said.

But with organoids, the mechanism of the drug can be actually tested. “Drugs that are already used for decades and it is still not known how they really work on the cells can be now investigated,” Jansen added, continuing that ultimately the hope is that this will facilitate the reduction of side effects.

Labs are also looking into genetic mutations, using CRISPR technology to edit genes. 

“If the protein of interest or any transcription factor of interest is present in your organic model, then yes, you can really do a lot in terms of disease,” Jansen said. She added that as labs’ creations become more advanced, the potential of disease modelling grows.

Funding for developing organoids and 3D modelling is available through the European research council (ERC) grants, as well as European Union’s rare disease network.

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[Edited by Gerardo Fortuna/Nathalie Weatherald]

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