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Stem cells treat diabetes without triggering immune response in mice

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Stem cells treat diabetes without triggering immune response in mice


The CD47 molecule, which tells the immune system not to attack

Pleiotrope

Stem cells have been developed that don’t provoke a destructive immune response, and they have been used to make pancreas cells to treat mice with a form of type 1 diabetes.

The result is a further step down the road to treating a range of medical conditions with tissues or organs that can be used “off the shelf”, instead of having to be made from scratch for each person.

“The vision is we have cells for anyone, anytime, anywhere,” says Sonja Schrepfer at Sana Biotechnology in San Francisco, California, the firm behind the approach.

It has been a long-standing medical goal to harness the regenerative powers of stem cells – cells that are similar to those in embryos that can be coaxed into multiplying and developing into different tissues. The hope is that they could be transplanted into people to treat a host of conditions, including heart attacks and strokes.

But cells taken from one person and put into another are usually killed by the immune system.

Most of the stem cell treatments in development would therefore either need people to take immune-suppressing drugs or require stem cells to be created from cells taken from the person receiving them. Such made-to-measure therapies would be more costly and could take several weeks to develop, which would be a problem if someone needed urgent treatment.

To get around those issues, Schrepfer’s team has developed a technique to genetically change cells so they become invisible to the immune system.

In this method, two genes that encode surface molecules that are required for the immune system to recognise the cells as “foreign” are removed. A gene is also added so the cells make a molecule called CD47, which normally tells the immune system not to attack.

The researchers first tested a “pluripotent” version of the cells – meaning they have the potential to be turned into multiple different tissues and organs – that was created from a rhesus macaque’s cells and then inserted into the leg muscles of four other rhesus macaques.

The cells survived with no signs of immune attack for up to four months, at which point the monkeys were euthanised. In contrast, cells that were inserted that hadn’t had the genetic changes were destroyed by the monkeys’ immune systems within three weeks.

Next, the stem cells were tested as a treatment for type 1 diabetes, which is caused by the loss of pancreas cells that make the hormone insulin. The stem cells were turned into pancreas cells and put into mice with the condition, with blood tests showing the cells reduced their diabetes symptoms.

Sana Biotechnology has previously shown that these genetically altered stem cells can be turned into heart muscle cells and a type of immune cell called CAR-T cells, which can be used to treat cancer.

But stem cells that aren’t invisible to the immune system have some advantages over those that are, says John Martin at University College London. For instance, so-called mesenchymal stem cells are visible to the immune system and seem to interact with it to promote the release of healing compounds.

And if any implanted stem cells happen to turn cancerous, immune cells need to “see” them in order to kill them, says Susan Kimber at the University of Manchester, UK. Nevertheless, the results are an important step towards making off-the-shelf stem cell treatments, she says.

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