David K.C. Cooper, MD, PhD, FRCS,
and Hidetaka Hara, MD, PhD
We will give a brief overview of the current status of cross-species organ and cell transplantation (xenotransplantation) and discuss current studies of corneal xenotransplantation.
The worldwide need for corneal transplantation far exceeds the supply of deceased human donor corneas. There is currently renewed interest in the possibility of using corneas from other species, especially pigs, for transplantation into humans.Current evidence indicates that the anatomical and biomechanical properties of human and pig corneas are similar. Since the cornea is an immune-privileged tissue, the human immune response to corneal cells may be less pronounced than to other cells.
Studies in animal models have documented both humoral and cellular immune responses that play roles in corneal xenograft rejection. The results obtained from the Tx of corneas from wild-type (i.e., genetically-unmodified) pigs into nonhuman primates have been surprisingly good, with graft survival >6 months.
We have demonstrated that the in vitro human humoral and cellular immune responses to genetically engineered pig corneal endothelial cells are greatly reduced compared to those to wild-type pigs. We will present the results of these studies.
Recent progress in genetic manipulation of pigs has led to the prospect that the remaining immunological barriers can be overcome. It is likely that xenograft survival in the absence of prolonged immunosuppressive therapy can be achieved by production of pigs with further genetic modifications. If this proves true, then corneal replacement may be a means by which the clinical utility of xenotransplantation will soon be demonstrated.The need is great, the logistics relatively simple, and the risks are potentially few.
Dr. David K. C. Cooper is the Director of the xenotransplantation (cross-species) research group at the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh. He taught Immunology at Harvard Medical School and Anatomy at the University of Cambridge in England. He worked with Professor Christian Barnard on the heart transplant program at the University of Cape Town.
Dr. Cooper has published almost 600 medical and scientific papers and chapters, most of which relate to heart transplantation or experimental xenotransplantation. He also co-authored a book on transplantation for the lay public "Xeno - The Promise of Transplanting Animal Organs into Humans."
Dr. Cooper's current work focuses on overcoming the rejection of pig organs and islets transplanted into primates and the induction of immunological tolerance to transplanted organs.
Dr. Hidetaka Hara graduated from the Kawasaki Medical School in Japan.
Dr. Hara is a Research Instructor of Surgery at the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh.
Dr. Hara completed his surgical residency and received his PhD in research in transplant immunology from Hiroshima University. He joined the research group of Dr. David K.C Cooper at the Thomas E. Starzl Transplantation Institute, University of Pittsburgh in 2004.
Dr. Hara has been involved in many aspects of transplantation research, including liver, kidney, heart, and islet xenotransplantation. Dr. Hara has recently made major contributions to corneal xenotransplantation, focusing on whether genetically engineered pig corneas can be protected against the human humoral and cellular immune responses.
Location and Address
Eye and Ear Institute, 5th floor Boardroom, 203 Lothrop Street
Pittsburgh, PA 15213