Written by:
Executive Director and Head of Bioscience Renal, AstraZeneca
Senior Scientist, Bioscience Renal, Early CVRM, AstraZeneca
Senior Director, Bioscience Renal, AstraZeneca
Kidneys have a complex structure which is critical to their function and this involves the cooperation of many different cell types. Studying single types of kidney cells grown in the lab has helped to advance our understanding of kidney health but we also need more advanced models to deepen our understanding of kidney function and to develop new medicines with greater potential to change the lives of people living with kidney disease – and this is where kidney organoids can help.
The purpose of our kidneys is to filter waste and excess water out of the blood so that it can be excreted as urine. The kidneys use pressure to first force most of the liquid and chemicals out of the blood and then selectively reabsorb anything that isn’t waste, to return it to the blood.
More than 10% of people worldwide1 are affected by kidney disease and it is responsible for over one million deaths each year,2 placing it in the top 10 causes of death worldwide.3 The causes of kidney disease can be genetic, due to the effects of diabetes, hypertension or inflammation in the kidneys.2,4 Kidney damage can also come about as a side effect of certain medicines.5
What are kidney organoids?
There are various ways to study kidney biology, including patient observation, animal models and in vitro models based on growing isolated cell populations in the lab. Naturally there is only so much we can learn about the biology of kidney disease from patients and we know that different types of cells behave differently when we study them together in combination. Work with animals has also contributed to many discoveries but they are not always an accurate reflection of human health and disease.
Choosing the right research models is vital to developing our understanding of kidney diseases and following the science to new therapies. We recently contributed to the International Society of Nephrology to develop guidance on the use of models in pre-clinical research. The guidance includes 25 key recommendations including encouraging the consistent use of clinically relevant models, considering organoids and other innovative model systems when appropriate, and considering the impact of traits such as sex on pre-clinical results.
Growing cells in the lab provides a better way to study human disease using human cells but it is still limited. Typically, it is only possible to study one type of cell at a time and the cells aren’t arranged or able to communicate in the way that they would inside the kidney. Until recently, the complexity of the kidneys has made it impossible to grow lab-based models that can be used to study how the kidneys work.
A particular challenge has been a type of cells called podocytes that play a critical role in separating waste from the blood. Podocytes are often injured in kidney diseases, making them a key focus of research. Reproducing these functions when podocytes are grown in isolation is a challenge and this makes it difficult to study them using established cell culture methods.6
Learn more from Miguel Carracedo Ortiz, Senior Scientist about why we use kidney organoids in research
Also known as ‘mini-kidneys’, kidney organoids can teach us much more about kidney function and they can be made using populations of human cells so they provide a better tool for studying disease. Despite the name, organoids aren’t really miniature organs, but normally look like three dimensional hollow balls of cells. They can be grown from just a few stem cells and include multiple different types of cells – including podocytes – which means they can behave much more like real kidneys.
With organoids we can better understand the interactions between different types of cells and explore how they work together within the kidney to carry out their essential functions. Thanks to gene editing technologies like CRISPR, it’s also possible to make organoids using cells carrying different genetic markers.7,8 This makes them an excellent way to understand the role of certain genes in causing disease and to investigate potential medicines for treating them.
The complexity of the kidney means it has been virtually impossible to create sophisticated models that duplicate the behaviour of the human kidney… Kidney organoids are miniature models derived from stem cells that closely mimic how the cells behave in the body.
In particular, we have used these technologies to create kidney organoids to study podocyte function and investigate potential podocyte-targeting treatments.7 We have also published work describing the creation of organoids that mimic the cyst growth observed in patients with autosomal dominant polycystic kidney disease, the most common genetic cause of kidney disease.8 These models are supporting our work on pre-clinical target validation and advanced drug development for renal diseases.
Using kidney organoids to develop medicines for kidney disease
Organoids represent an exciting way to study the effects of novel treatments on aspects of human biology. While they are unable to completely replicate the situation inside a human body, they offer much richer insights into how treatments could affect their target organ and can be used to explore how those responses could be altered by unique aspects of a patient’s biology.
As such, organoids provide a vital tool in helping to bridge the gap between animal models and early-stage clinical trials and are helping us to develop a deeper understanding of the efficacy, risks and benefits of new treatments. As a result, safe and effective treatments can be developed faster, ultimately allowing us to deliver more life-changing medicines to patients.
