Could fat help make more kidneys suitable for transplant?
Fat has notoriously been given a bad name. But what if it could be used for good? With funding from Kidney Research UK, Dr Rashida Lathan and her colleagues at the University of Glasgow are investigating whether fat cells could repair damaged kidneys and make more organs suitable for transplant.
More donor kidneys are desperately needed
In the UK, over 5,000 patients are waiting for a kidney transplant. Often, if organs come from older, sicker donors, or donors who have died, they don’t function well after transplant or can’t be used because they are too damaged. This is because these kidneys are susceptible to ‘ischaemia-reperfusion injury’ during the transplant procedure – tissue damage caused when the blood supply returns to a tissue that has been starved of oxygen.
“We have kidneys coming in but they're too poor quality to use as donor organs,” explains Rashida. “The goal of this research is to repair damaged kidneys so more donated organs are fit for transplant and more patients can have this life-saving treatment”.
Using fat cells as treatment
Adipose-derived regenerative cells (ADRCs) are cells that are taken from body fat. They are made up of a mixture of different cell types, including a high proportion of stem cells. ADRCs are already being used in clinical trials to repair other organs, such as heart and liver. After some promising results from animal studies, Rashida and her team believe they may also be able to rescue damaged donor kidneys.
The team have developed a rat model that mimics the human ischaemia-reperfusion injury. When they injected just one dose of ADRCs from the rats’ own fat tissue, into their renal arteries, they saw a striking reduction in kidney damage.
There are many advantages to using ADRCs to repair kidneys. “These cells are extremely easy to access – everyone's looking to get rid of fat” explains Rashida. “Machines have already been developed for easy use within hospitals and they can quickly extract ADRCs from fat tissue, so the whole process of extraction and transplant could be done in the same building on the same day. ADRCs also contain a lot more stem cells than bone marrow, and the fact that these cells can be taken from patients’ own bodies makes it a safer treatment, as you are not introducing something foreign into the body.”
How do ADRCs repair kidneys?
Rashida is now investigating exactly how ADRCs improve kidney structure and function. She believes they release (secrete) molecules that signal to surrounding kidney cells.
To help her understand which molecules have a therapeutic effect on the kidneys and which cells release them, Rashida has been studying which proteins are being made in individual ADRCs. She has found several potential therapeutic molecules – and many are known to be important for repairing other parts of the body.
One question raised by this research is whether the signalling molecules could be a therapy by themselves or whether the actual cells are needed. “We don’t know if delivery is as important as secretion,” explains Rashida. “Our data shows ADRCs accumulate mainly within the glomeruli [filtering units] of the kidney, so that contact and targeting might actually be essential to deliver the therapy.”
As well as the rat model, Rashida and her colleagues also work with 3D organoids – miniature kidneys grown in a dish. These are used to test the effects of treatment with either molecules or individual types of cells from the ADRC cell mixture to understand more about the mechanisms involved.
How close is this research to the clinic?
Alongside the rat and organoid model work, Rashida is also working with Robert Pearson, a PhD student at the University of Glasgow, to test the effect of ADRCs on human kidneys too damaged to be used for transplant but donated to research. They will investigate the effect of treating these kidneys with ADRCs as well as normothermic perfusion: connecting the kidney to a machine that flushes the organ with oxygenated blood.
Rashida’s work so far suggests that, along with normothermic perfusion, injecting a patient’s own ADRCs through the renal artery during the transplant procedure may improve both the function of the transplanted kidney and the outcome for the patient.
Although early results are very promising, there are more steps to provide important safety data before clinical studies in humans, which we would expect in the next 5–10 years.