A transplant can be a lifesaving procedure for many people across the United States. In fact, according to the Health Resources & Services Administration, 36,528 transplants were performed in 2018. However, as of January 2019, the number of men, women, and children on the national transplant waiting list is over 113,000, with 20 people dying each day waiting for a transplant and a new person being added to the list every 10 minutes.
Before considering a transplant, there needs to be an immunological match between the donated tissue and/or blood stem cells and the recipient. To put it simply, a “match” indicates that the donor’s cells will not be marked by the recipient’s immune cells as foreign and begin to attack it, a process known as graft-versus-host disease. Unfortunately, these matches can be challenging to find, particularly for some ethnic minorities. Often times, immunosuppression drugs are also needed in order to prevent the foreign cells from being attacked by the body’s immune system. Additionally, chemotherapy and radiation are often needed as well.
Fortunately, a CIRM-funded study at Stanford has shown some promising results towards addressing the issue of matching donor cells and recipient. Dr. Irv Weissman and his colleagues at Stanford have found a way to prepare mice for a transplant of blood stem cells, even when donor and recipient are an immunological mismatch. Their method involved using a combination of six specific antibodies and does not require ongoing immunosuppression.
The combination of antibodies did this by eliminating several types of immune cells in the animals’ bone marrow, which allowed blood stem cells to engraft and begin producing blood and immune cells without the need for continued immunosuppression. The blood stem cells used were haploidentical, which, to put it simply, is what naturally occurs between parent and child, or between about half of all siblings.
Additional experiments also showed that the mice treated with the six antibodies could also accept completely mismatched purified blood stem cells, such as those that might be obtained from an embryonic stem cell line.
The results established in this mouse model could one day lay the foundation necessary to utilize this approach in humans after conducting clinical trials. The idea would be that a patient that needs a transplanted organ could first undergo a safe, gentle transplant with blood stem cells derived in the laboratory from embryonic stem cells. The same embryonic stem cells could also then be used to generate an organ that would be fully accepted by the recipient without requiring the need for long-term treatment with drugs to suppress the immune system.
In a news release, Dr. Weissman is quoted as saying,
“With support by the California Institute for Regenerative Medicine, we’ve been able to make important advances in human embryonic stem cell research. In the past, these stem cell transplants have required a complete match to avoid rejection and reduce the chance of graft-versus-host disease. But in a family with four siblings the odds of having a sibling who matches the patient this closely are only one in four. Now we’ve shown in mice that a ‘half match,’ which occurs between parents and children or in two of every four siblings, works without the need for radiation, chemotherapy or ongoing immunosuppression. This may open up the possibility of transplant for nearly everyone who needs it. Additionally, the immune tolerance we’re able to induce should in the future allow the co-transplantation of [blood] stem cells and tissues, such as insulin-producing cells or even organs generated from the same embryonic stem cell line.”
The full results to this study were published in Cell Stem Cell.