Stem cells treat diabetes without triggering immune response in mice

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CD47 molecule, which tells the immune system not to attack

CD47 molecule, which tells the immune system not to attack


Stem cells have been developed that do not provoke a destructive immune response, and they have been used to make pancreas cells to treat type 1 diabetes in mice.

The result is another step on the road to treating a range of medical conditions with tissues or organs that can be used “off the shelf,” rather than being created from scratch for each individual.

“The vision is that we have cells for anyone, anytime, anywhere,” says Sonya Schreifer at Sana Biotechnology in San Francisco, Calif., the firm behind the approach.

It has been a long-standing medical goal to harness the regenerative powers of stem cells – cells similar to those in the embryo that can be coaxed to multiply and develop into different tissues. The hope is that they could be implanted in people to treat a range of conditions, including heart attacks and strokes.

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

Most stem cell treatments in development either require people to take immune-suppressing drugs or create stem cells from cells taken from the person receiving them. Such improvised treatments would be more expensive and could take several weeks to develop, which would be a problem if someone needed immediate treatment.

To address those issues, Schrepfer’s team has developed a technique to genetically alter cells so that they become invisible to the immune system.

In this method, two genes that encode surface molecules that are necessary for the immune system to recognize 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 turn into many different tissues and organs — that was made from cells from one rhesus macaque and then from four other rhesus macaques. was inserted into the muscles of the leg.

The cells survived for four months with no signs of immune attack, at which point the monkeys were euthanized. In contrast, cells that were inserted that did not contain the genetic changes were destroyed by the monkeys’ immune systems within three weeks.

Subsequently, stem cells were tested as a treatment for type 1 diabetes, which is caused by damage to the pancreas cells that make the hormone insulin. After the stem cells were turned into pancreas cells and put into mice with the condition, blood tests showed the cells reduced their diabetes symptoms.

Sana Biotechnology has previously shown that these genetically modified stem cells can be changed heart muscle cells and a type of immune cell called CAR-T cells, which can be used cure cancer,

But stem cells that are not invisible to the immune system have some advantages over them, says John Martin in University College London. For example, so-called mesenchymal stem cells are visible to the immune system and interact with it to promote the release of healing compounds.

And if any transplanted stem cells happen to turn into cancer, immune cells need to “see” them in order to kill them, he says. Susan Kimber at the University of Manchester, UK. Still, the results are an important step toward creating off-the-shelf stem cell treatments, she says.



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