We propose to develop a bioengineered, implantable Thymus gland to treat patients who suffer from diseases caused by immune deficiency. A healthy immune system is essential to prevent infections, cancer and autoimmune diseases such as diabetes, rheumatoid arthritis and inflammatory bowel disease. The Thymus converts blood-forming stem cells into T cells that protect against infection and cancer, but which have also been “educated” to not react against normal tissue and cause autoimmune disease. With aging, the Thymus shrinks, and normal T cell production falls. The problem is even worse in patients who have had chemotherapy or viral infections such as HIV. The most severe form of thymic insufficiency is in babies in which the thymus never develops, a lethal condition called Di George Anomaly (DGA). Our team has devised a novel method to produce a human thymus that can be surgically implanted. We culture different components of the human thymus and engineer them to enhance their growth and function. We have shown that after implantation into mice, the new thymus can produce functional human T cells. Our first goal is to scale-up the method for clinical treatment of babies with DGA. We then plan to broaden the application of this technology by producing Thymic implants from induced pluripotent stem cells, providing an inexhaustible supply of matched tissue for treatment of a variety of immune deficiencies and autoimmune diseases that arise in adult life.
The goal of this proposal is to develop a bioengineered thymus gland to provide an environment for the production and control of a healthy immune system. Immune dysfunction provides the catalyst for many of the major chronic diseases that plague our society. Each year, tens of thousands of Californians are diagnosed with autoimmune diseases such as Type I Diabetes, Multiple Sclerosis, Systemic Lupus Erythematosus and rheumatoid arthritis. Over 21,000 Californians and 100,000 Americans are estimated to be in need of organ donation for life threatening diseases. Heavy suppression of the immune system is required to prevent rejection of transplanted organs resulting in many serious side effects for patients. For the thousands of patients who undergo bone marrow transplantation for leukemia and genetic diseases, the most common problem is immune-mediated graft versus host disease which in turn damages the thymus and leads to life threatening infections. We propose an entirely novel approach to regenerate the damaged thymus, by providing a microenvironment that can be engineered to control the immune system after surgical implantation.