A one-off injection of cells could be a long-sought solution to the problem of the body rejecting an organ transplant.
The first person who may have benefited from this approach is an Italian man who had a . He has been completely tolerating his new organ for 19 months without anti-rejection medicines.
Transplants can be life-saving, but to stop the donor organ being rejected by the recipient’s immune system, people have to take several drugs that have serious side effects, including cancer and infections – and they don’t always work. The new treatment involves injecting mesenchymal stromal cells. This can be done the day before the transplant and seems to damp down the recipient’s immune reaction in a way that “teaches” the body to accept the different tissues.
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This type of cell can come from a variety of sources. Giuseppe Remuzzi at the Mario Negri Institute for Pharmacological Research in Milan and his team took them from the recipient’s bone marrow, multiplied them in the lab, and reinjected them. After two years, blood tests suggested he was tolerating his new kidney so his anti-rejection medicines were gradually reduced over about five years and then stopped.
But it isn’t clear if the cells were definitely responsible; in a second person given the treatment, blood tests didn’t show tolerance. A few previous kidney recipients have developed tolerance to their new organ spontaneously – so perhaps the Italian man’s response was another of these rare cases, says Emily Thompson at Newcastle University in the UK, who wasn’t involved in the work. If the cells really were responsible, she says “it would be a pretty big deal”.
Although the success of the treatment in the first case is unproven, studies by other groups suggest these kinds of cells can promote at least some level of tolerance. When six Dutch kidney transplant recipients showing initial signs of rejection were injected with the cells twice as an emergency treatment, they later showed signs of improved donor organ tolerance in blood tests.
The team behind the Dutch result has carried out a 10-person study using a post‑transplant treatment with mesenchymal stromal cells from healthy donors. These have the advantage that they can be prepared in advance. The results aren’t yet published, but are promising, says Marlies Reinders at Leiden University Medical Center in the Netherlands. She believes that these cells aren’t powerful enough to let most people stop all their anti-rejection medication, but they should allow some reduction. “There would be less side effects,” she says.
A trial in China that used mesenchymal stromal cells instead of other kinds of anti-rejection drugs found they led to fewer episodes of rejection in 156 recipients of kidneys.
The cells may not have to be generated anew each time they are needed. US biotech firm Athersys is developing an off-the-shelf therapy using cells called MAPCs, thought to have similar immune-suppressing effects. Thompson’s team is trying a different approach of applying these cells to kidneys kept alive outside the body.
