Stem cell research allows for mismatched kidney transplants

Donating a kidney may save a person's life - but only if the conditions are precise.

Kidney donors must be related and immunologically matched to their donors and even then, the recipient must take a lifetime of anti-rejection medications, which dont guarantee the organ won't be rejected.

But a new clinical trial from Northwestern Memorial Hospital in Chicago, Ill. has shown how stem cells can be used to trick a recipients immune system into believing the new organ has been part of that persons body all along.

The breakthrough has the potential to eliminate both the risks associated with kidney transplantation and the need for anti-rejection medications within one year after surgery.

Its the holy grail of transplantation, said lead author Dr. Joseph Leventhal, transplant surgeon at Northwestern Memorial Hospital and associate professor of surgery and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine in Chicago, Ill. This notion of being able to achieve tolerance through donor derived cells has been around for more than 50 years, but its translation to the clinic has been quite elusive. This article details the first successful attempt of this in mismatched and unrelated kidney recipients.

The research was published Wednesday in the journal Science Translational Medicine, and it is the first study of its kind in which the donor and recipient were not related and did not have to be immunologically matched. Only 25 percent of siblings are immunologically identical, severely limiting the possibility of being a kidney donor.

The procedure worked by extracting a little bit more from the kidney donor than just their kidney. They also donated part of their immune system. About one month before surgery, bone marrow stem cells were collected from the donor and then enriched with facilitating cells becoming stem cells that will ultimately fool the donors immune system allowing the transplant to succeed.

One day after the kidney transplant occurs, the facilitating cell-enriched stem cells are also transplanted in the recipient, which then prompts the formation of stem cells in the bone marrow. This then causes specialized immune cells similar to the donors immune cells to develop, creating a dual bone marrow system environment, so both the donors immune system and the recipients immune system function inside the persons body.

Leventhal said that the ultimate goal is for the recipient to initially take anti-rejection medications but then slowly wean off of them within a year. According to Leventhal, the drugs come with their own share of negative side effects.

The foundation of clinical transplantation revolves around the use of medicines and suppressive drugs to control the immune system, Leventhal said. These drugs have been very successful in reducing the rates of loss of organs due to acute rejection where side effects include increase risk of infection and cancer, and metabolic side effects, such as the increase risk of hypertension and bone disease. But the drugs themselves are potentially harmful to the organs we transplant. Despite our ability to reduce rates of acute rejection, most individuals go on to lose organs because of chronic (long-term) rejection.

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Stem cell research allows for mismatched kidney transplants

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