About 77 organ transplants are performed each day in the U.S., and more than 101,000 people are on a wait list for body parts such as hearts, skin and veins, according to the Mayo Clinic. But even for those lucky 77, complications are worrisomely common. Forty percent of lungs, for example, are rejected within the first year of surgery.
Pierre Delaere, a surgeon at the University Hospital Leuven in Belgium, hopes to improve the mediocre statistics by developing new methods of transplanting organs. His latest challenge: the trachea—notorious for rejection by the body. As described recently in the New England Journal of Medicine, Delaere and colleagues implanted a donated windpipe into a woman's arm, allowing the body to acclimate to it for a couple of years before transplanting the organ into her throat. During this time, the patient's own cells covered the trachea, and it became familiar to her body's immune system.
As a result of the procedure, the patient was able to stop taking an immunosuppressant, a drug that stifles the body's natural defense system. With the immune system weakened, the cells charged with attacking foreign entities can't function; this forces the body to accept organ transplants, but also leaves patients extremely vulnerable to disease. Patients who have undergone organ transplants typically have to take immune system–suppressing drugs permanently and suffer side effects such as viral warts, memory loss and weakened bones, all of which alter their quality of life, says Craig Morrell, who studies transplants at the University of Rochester. "You have to live a protected life, which is difficult," he says, "and immunosuppressants are expensive over the long term, too."
Delaere's research is part of a larger scientific endeavor to get away from immunosuppressant drugs and expand into novel transplant methods. Another such effort targets T cells, the cells in the immune system that attack foreign organs, but in such a way that their aggressive defense is quashed for a short time only.
Scientists at Sydney's Garvan Institute of Medical Research used a complex molecule to boost the number of nonaggressive, regulatory T cells in the body of a mouse while it underwent a transplant. This effectively muffled the "killer" form of T cells long enough for the body to accept the new tissue. After a 14-day period, the T cells balanced themselves out once again and the mouse's biological defense returned to normal. Morrell is enthusiastic about this progress. "These regulatory T cells dampen down the immune system's response," he says. "If you can manipulate your own body to try to quiet down the T cell response, it's a great idea."
Other techniques involve transplanting bone marrow or stem cells, along with the target organ, which effectively fools T cells into believing the organ is from a familiar body. In an experimental study done in 2008, doctors at Massachusetts General Hospital denied a patient immunosuppressants and instead gave her some of her organ donor's bone marrow. In the five years since her transplant, the patient still hasn't resorted to anti-rejection drugs. Using mice as test subjects for another method of cell trickery, researchers at the University of Iowa and the Iowa City Veterans Affairs Medical Center took embryonic stem cells from the organ donor, adapted them into another type of stem cell and injected those altered stem cells into the patient. This effectively readied the patient's immune system for a new organ.
But others think immunosuppressants, which have played a valuable role in the history of organ transplantation, shouldn't be discounted just yet. Perhaps, researchers at Stanford University School of Medicine say, instead of eliminating immunosuppressant drugs, scientists can fiddle with the drugs' design to limit undesirable side effects.
The pharmaceutical company Pfizer created a drug that inhibits a molecule that orders immune cells to attack. Researchers hope the drug will suppress T cells for a transplant without disabling the body's immune system entirely or subjecting patients to the procedure's side effects. So far, scientists have only tested this experimental drug on monkeys but hope it marks the advent of drugs that target specific problem areas in organ rejection.
Morrell's research also looks at one such problem area: platelets, blood cells involved with clotting, which are full of immune regulators that may contribute to all stages of the organ-transplant process. He wants to see how these key components of blood are involved with rejection.
"Now that research has advanced, the role other cells have in driving immune response is a bigger problem to address," Morrell says. He thinks that scientists need to learn more about the small cellular components and interactions involved in both transplant success and rejection and how immune cells are activated and regulated.
Furthermore, since people are living longer with transplants, new problems are being created for the field. For instance, researchers see that, over time, patient blood vessels begin to change in a manner similar to atherosclerosis, the buildup of fatty material on artery walls, which ultimately leads to transplant rejection. "We're starting to see new problems, which is good because that means transplants are surviving longer," Morrell says.
In the long run, scientists are making strides toward growing new organs using stem-cell technology—lung and heart tissue, for example, that could provide patches to damaged organs, eliminating the need for a transplant altogether. But for now, surgeons still have to rely on donor organs, which means manipulating what's happening on a cellular level in order to convince bodies they're a natural fit.