Designer kidney cells engineered to release insulin could one day be put in a capsule and implanted under the skin to treat both type 1 and type 2 diabetes, according to scientists.
A team of researchers in Switzerland have successfully genetically altered a type of human kidney cell called HEK to enable it to sense glucose levels in the blood and produce insulin as required.
The team at science and technology University ETH in Zurich says the approach is simple but the key is that the new cells, like their natural model, act as both sugar sensors and insulin producers.
So far the process has worked in mice by successfully controlling blood glucose levels and they believe that if the process is found to be safe and effective in people with diabetes in the future they could potentially be used as a new treatment.
The researchers led by Professor Martin Fussenegger of the Department of Biosystems Science and Engineering (D-BSSE), took a different approach to other approaches which have been based on stem cells which scientists allowed to mature into beta cells either by adding growth factors or by incorporating complex genetic networks.
For their new approach, the ETH researchers used a cell line based on human kidney cells, HEK cells. The researchers used the natural glucose transport proteins and potassium channels in the membrane of the HEK cells. They enhanced these with a voltage dependent calcium channel and a gene for the production of insulin and GLP-1, a hormone involved in the regulation of the blood sugar level.
In the artificial beta cells, the HEK cells’ natural glucose transport protein carries glucose from the bloodstream into the cell’s interior. When the blood sugar level exceeds a certain threshold, the potassium channels close. This flips the voltage distribution at the membrane, causing the calcium channels to open. As calcium flows in, it triggers the HEK cells’ built-in signalling cascade, leading to the production and secretion of insulin or GLP-1.
The initial tests of the artificial beta cells in diabetic mice revealed the cells to be extremely effective. ‘They worked better and for longer than any solution achieved anywhere in the world so far. When implanted into diabetic mice, the modified HEK cells worked reliably for three weeks, producing sufficient quantities of the messengers that regulate blood sugar level,’ said Fussenegger.
The team has also created beta cells that had been grown from stem cells from a person’s fatty tissue but as this technique is expensive since the beta cells have to be produced individually for each patient, they believe that this latest solution would be cheaper as the system is suitable for all diabetics.
The cells will now undergo various clinical trials before they can be used in humans. Trials of this kind are expensive and often last several years, but Fussenegger reckons that if the cells clear all the hurdles, they could reach the market in 10 years.
Dr Emily Burns, research communications manager of charity Diabetes UK, described it as a promising area of research. ‘We can already replace the cells in the pancreas that are damaged in type 1 diabetes by using cells taken from donated pancreases, but one of the issues with this approach is that there aren’t enough donors. That’s why research like this is so important: finding ways to produce an unlimited supply of pancreatic cells, or cells that act like them, in the lab,’ she said.
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