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Organ Replacement Technologies: A New Frontier: The Future of Organ Replacement


The Future of Organ Replacement

At the conclusion of the symposium, a panel of speakers addressed 3 main questions regarding the future of organ transplantation and organ replacement: (1) What are the options?, (2) What should we be doing?, and (3) How do we get there? David M. Briscoe, MD,[20] of Harvard Medical School in Boston, Massachusetts, helped Medscape put the panel's conclusions in perspective: "Implantable devices, cellular transplantation, stem cell biology, and organogenesis might ultimately become future options in both the prevention and treatment of cardiac, liver, and kidney diseases. This symposium was highly innovative and exciting, and clearly is the first of many that in the future may suggest that it will be possible to replace organ function with all of the above."

Most feasible in the short term, according to Dr. Briscoe, is cardiac replacement therapy with cardiac assist devices. First-generation assist devices have achieved the goal of 2-year survival, and future second-generation devices may further prolong survival. In the future, other promising options include myoblast therapy and the use of stem cells, especially those of the hemangioblast lineage, which promote healing via angiogenesis.

More complex applications, which require significantly more development, include lung replacement therapy with implantable artificial lungs, cellular transplantation, and xenotransplantation. A major issue in hepatocyte transplantation is finding an infusion method that will optimize engraftment. As is evident from the work of Dr. Atala and Dr. Hammerman, there is greater hope for human kidney replacement. Human islet transplantation is already established, while current research suggests that xenogeneic porcine islets may also be useful in diabetes treatment.

National Institutes of Health (NIH) Funds Are Dwindling

"The challenge is how to keep the area funded," Dr. Briscoe said. "Decreased NIH funding may have a potential long-term effect. The transplantation research program costs one tenth of what it would cost to build a new space shuttle, but the potential impact is so far-reaching." Dr. Platt agreed that it will take more than venture capital to fund the field of organogenesis, and that the NIH should fund it until it becomes self-sustaining. His justification is that "almost every advance in medicine leads to a greater need for organ replacement."

Although there are no plans for NIH funding of an artificial kidney or liver, the annual budget for heart replacement is $10 million. Because 1000 steps are involved in total artificial heart implantation, the panel suggested that the $10 million is a modest investment considering the complexity of the process.

"Everything we talked about will eventually come to fruition; historically this has been true and we asked the same questions and worried about the same things," said Marshall I. Hertz, MD,[20] a Professor of Medicine at University of Minnesota Medical School. "The cheapest thing to do is to let people die, but Western society has rejected this philosophy."

Although the device companies are sitting on the sidelines to see what the market will bear, Dr. Rose noted that Medicare would approve device insertions. "For xenotransplantation, the bar is higher than it was," he said. "Unless the knockout pig succeeds, there is no single magic bullet."

From a regulatory viewpoint, Dr. Rose stressed the need to determine whether various technologies improve net health outcomes, including survival and QOL (personal communication, 2/16/03). He is optimistic about the potential of stem cell technologies, because "the best model is still people, especially for islet cells." Under relatively low immunosuppression, it takes 100 pigs to achieve normoglycemia in 1 patient.

"Everyone could use more research funding, but there are some special considerations with respect to future funding for transplant research," Charles G. Orosz, MD, a Professor of Surgery and Pathology at Ohio State University Medical Center in Columbus, told Medscape (personal communication, 2/21/03). "The discipline has entered a period of significant reevaluation and adjustment regarding its primary conceptualizations and clinical practices." He cites growing interest in minimizing immunosuppressive drug use, which could be facilitated by greater study of the role of alloreactive B cells in acute and chronic rejection. Applications of allograft biology may extend beyond immunology into the realms of physiology, inflammation, and tissue repair and remodeling. "Transplantation could be considered as an entity that has successfully survived its birth, grown impressively throughout its childhood, and now enters its adolescence," Dr. Oroscz says. "It has the potential to be highly productive as an adult, but its maturation still requires nurturing."

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