Novel stem cells method may eliminate need for antirejection drugs in transplants

Surgical researchers at the University of Washington, Seattle, have pioneered a method using stem cells that may one day eliminate the need for antirejection drugs in transplants. Primary investigator David Mathes, MD, FACS, and his research fellow Jeff Chang, MD, MS, presented their findings today at the 2011 Clinical Congress of the American College Surgeons. Two groups of patients who might one day benefit from this early research breakthrough are hand and face transplant recipients. To date, survival of these transplants has depended on administering high-dose drugs to patients that suppress the immune system like those used in major organ transplants. However, these drugs are expensive and have a multitude of side effects, the researchers explained.

The surgeons performed simultaneous transplants of vascularized composite allografts—transplanted tissue with the blood vessels intact—and stem cells in four dogs followed by a short course of immune-suppressing drugs. All four dogs accepted the grafts without complications. After about a month, the researchers discontinued all immune system suppressing drugs. One dog rejected its stem cell transplant 10 weeks after the operation, but continued to tolerate the composite allograft for over one year without immunosuppression.

The other three dogs tolerated both stem cells and composite allografts for over one year. The investigators also performed vascularized composite allograft transplants without the stem cells on three other dogs. All three rejected the transplants after immune-suppressing drugs were stopped.

"If this technique works and proceeds into a clinical model, we would be able to transplant patients with either face or hands or even solid organs without the need for long-term immunosuppression drugs," according to Dr. Chang. Physicians prescribe these drugs to people who have undergone hand and face transplants because organ transplant recipients, such as those receiving a liver or kidney, must take high-dose drugs to suppress the immune system and stave off organ rejection. Innovators of the hand and face transplants have followed this protocol to similarly prevent tissue rejection.

However, the side effects of these drugs have been widely reported. Kidney transplant recipients, for example, have a heightened risk of developing diabetes and hypertension. These drugs also raise the likelihood of infections and malignancy in all transplant recipients, Dr. Chang explained. Moveover, the American Society of Transplant Surgeons has estimated that immune-suppressing drugs can cost up to $25,000 a year per person.

While solid organ transplants are considered life-prolonging procedures in which the benefits outweigh the drug side effects, Dr. Chang noted that hand and face transplants do not fit this category. "Face and hand transplants are not life-saving procedures, so not subjecting these patients to the risks of immunosuppression would certainly be beneficial to them," Dr. Chang said.

Although this research is still in an early phase, an important new finding the University of Washington study unveiled is the role that stem cells play in making the body tolerant of transplanted tissue, Dr. Chang said. "It's interesting that you can modulate the immune system in such a way that you can transplant other cells into the recipient and the recipient becomes tolerant of them," he said.

The study involved vascularized composite allograft transplants matched to the recipient's tissue type. The next step is to attempt transplants in what Dr. Chang called a "mismatched" setting—where the donor and recipient tissue types do not necessarily match. "If we can get this to work in a mismatched setting it would be more clinically relevant," Dr. Chang said.

Dr. Mathes and his collaborators at the Fred Hutchinson Cancer Research Center are attempting to develop this experimental model into a more clinical model for humans. The use of a canine model for this research is significant because large animals more closely resemble human anatomy and physiology with regard to composite allograft transplants, whereas "trying this method in small animals, such as laboratory mice, would be more difficult to translate into humans," Dr. Chang explained.

Although the researchers embarked on developing this technique with hand and face transplants in mind, simultaneous mismatched tissue and stem cell transplantation may also hold promise for solid organ transplants. "If we extend this technique into solid organ transplantation, it would assist with a major problem; whether or not you need a complete match," Dr. Chang said. "The other problem is supply and demand. If we can break the immunological barriers in such a way that would let us transplant a mismatched kidney, it would help greatly with the shortage of organs."