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| Cardiothoracic Transplantation Laboratory |
40 YEARS OF SURGERY INNOVATIONS AND RESEARCH
The Cardiothoracic Transplantation Laboratory at Stanford Medical School was founded in the early 1960's by transplantation pioneer Dr. Norman E. Shumway to develop and refine the orthotopic cardiac transplant model. Innovative thinking, skillful application of surgical technique, as well as dedication and perseverance towards achieving difficult goals, have been a trademark of this laboratory since its inception. From the first long-term surviving cardiac transplant performed by Dr. Shumway's Stanford team in 1968 to the development of new immunosuppressive agents in the 1970's, the first successful heart-lung transplant in 1981, and the ongoing development of cutting-edge technology including gene therapy and stem-cell models, the Stanford Transplantation Laboratory has remained one of the world's pre-eminent labs in the increasingly complex and dynamic field of cardiothoracic organ transplantation and transplant immunology.
The transplant laboratory has offered first-rate surgical and academic training to hundreds of young residents, medical students, and scientists over the past four decades, including many internationally recognized leaders in the field. After Dr. Shumway and Dr. Richard Lower, assisted by veterinarian Raymond Stofer, developed the working canine cardiac transplant model that led to the first clinical transplant at Stanford in 1968, Dr. Edward Stinson joined the research team and subsequently became a technically gifted and medically brilliant transplant surgeon who helped guide the fledgling transplant program at Stanford through its early years. In the early 1970's, Drs. Philip Oyer, Philip Caves, and Randall Griepp rotated through the lab before completing surgical training and becoming prominent transplant surgeons in their own right. Dr. Caves' invention of the cardiac bioptome in the laboratory brought a vitally important technique, still regarded as the "gold standard" for evaluating rejection, into the clinical world.
In the late 1970's two gifted young surgeons with exceptional vision utilized the laboratory to pioneer more exciting research with direct clinical applications. Dr. Stuart Jamieson came over from the United Kingdom and introduced the rodent heterotopic cardiac transplant model to the laboratory, and also a new immunosuppressive agent, Cyclosporine A. Both the model and the drug became staples in the laboratory for years to come. Dr. Bruce Reitz began using a primate model for combined heart and lung transplantation, which led directly to the first clinical heart-lung transplant at Stanford in 1981 and the ultimate establishment of single- and double-lung transplantation. To this day, Stanford is recognized as one of the elite centers in the world for heart, heart-lung, single- and double-lung transplantation.
As large animal models became more costly, the transplant lab began utilizing rodent models more extensively in the 1980's. These models allow investigating the cellular and molecular aspects of acute and long-term cardiac and lung graft rejection, reperfusion injury graft coronary artery disease, and cardiogenesis in infracted heart tissue. The various rodent transplant models developed over the past two decades include:
- heterotopic heart transplantation
- orthotopic lung transplantation
- aortic and venous interpositional grafting
- LAD (left anterior descending) coronary arterial ligation
Recently an improved "beating " heterotopic vascularized cardiac transplant procedure has been developed to allow more accurate physiological monitoring grafts placed in the abdominal area.
Present
In 1990, Lab Director Dr. Vaughn Starnes enlisted the academic talents of Dr. Carol Clayberger to establish a transplantation research laboratory where trainees could perform immune functional assays, tissue culture, and molecular biology analyses as the study of graft function after transplantation became more sophisticated. Today, with the help of Senior Research Scientist Dr. Eugenia Fedoseyeva, residents, medical fellows, and students have access to a variety of cellular and molecular techniques including immune and traditional histology, FACS analysis, T cell ELISPOT, imaging techniques for monitoring cell and tissue transplantation (14.5 MHz Echocardiography, MRI (4.7 Tesla), bioluminescence), and others.
In 1993, Dr. Robert C. Robbins assumed directorship of the Transplant Laboratory and has worked tirelessly to maintain the high standards of his predecessors as he enters his third decade overseeing this dynamic and productive laboratory. Over the past ten years, Dr. Robbins has initiated numerous collaborations with fellow investigators in other laboratories at the Medical School to more effectively understand the complex nature of heart failure.
The advent of tissue engineering has led to the introduction of various heart-failure models to investigate regeneration of injured heart tissue. Transplant laboratory researchers have implemented a technique of ligating the left anterior descending (LAD) coronary artery of a rodent, then transplanting stem cells into the infarcted region to re-grow tissue. Collaborative efforts with investigators using Magnetic Resonance Imaging (MRI), ultrasound, bioluminescence, and echocardiography have dramatically improved evaluation of stem cell transplantation as well as physiological monitoring of graft and vessel transplants in all rodent models employed in this laboratory.
Today, the Laboratory continues to serve the dual purpose of training young surgical residents in microvascular techniques and conducting well-conceived, cutting-edge research pertinent to cardiothoracic organ transplantation, graft rejection, graft coronary artery disease, cardiogenesis, molecular biology, gene therapy, and stem cell transplantation. The Laboratory generates dozens of peer-reviewed journal publications annually and attracts surgery residents, academic scholars, and students from all over the world. The same principles of vision, perseverance, rigorous scientific investigation, and application of innovative technologies that guided Dr. Shumway in founding the Laboratory nearly five decades ago have served his successors to maintain its respected status among cardiac research groups throughout the world.
By Grant Hoyt
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