About Us
Our Research
Miami Transplant Institute will attack the two main challenges in transplantation - tolerance and organ availability - by bringing together under one roof a broad array of transplant research programs and a long track record of large scale clinical trials for new therapies.
The Promise of Solving the Mystery of Tolerance
Immune tolerance can be natural ('self tolerance'), which is why our immune system does not turn on itself. If this type of tolerance fails to occur, a person may develop one of hundreds of known autoimmune diseases like juvenile diabetes or rheumatoid arthritis.
Induced tolerance is the tolerance that occurs when scientists attempt to re-educate a patient's immune system to accept a transplanted organ or tissue as 'self' and side-step rejection altogether, including the unwanted side effects of powerful agents that today must accompany all transplants.
While organ transplantation is indeed the ultimate life-saving therapy for many types of diseases that cause end stage organ failure, performing transplants without having to rely on anti-rejection medication remains a daunting task. The concept of 'tolerance' crosses a wide array of medical disciplines, including surgery, immunology, transplantation, and molecular biology. However, relatively few experimental concepts have successfully made their way to the clinic.
How can scientists establish an immunologically tolerant state, allowing the specific acceptance of transplants from donors to recipients, while at the same time leaving normal immunity intact so that a person can still fight off unwanted antigens and diseases?
How can scientists establish an immunologically tolerant state, allowing the specific acceptance of transplants from donors to recipients, while at the same time leaving normal immunity intact so that a person can still fight off unwanted antigens and diseases?
Answering these questions is a key goal of MTI research. Our success would eliminate the need for chronic immunosuppression and its unwanted side effects. It would open up transplantation to a wider array of candidates who are currently unable to endure rigorous regimens of immune system depletion and reconstitution through anti-rejection medications.
The challenge of defining tolerance-inducing regimens that are both safe and effective in the clinical arena remains one of the principle challenges of medicine today.
The Promise of Regenerative Medicine
Currently, most organs used for transplant come from deceased donors. Death, however, produces profound alterations in organs characteristics that make them far inferior to organs harvested from living donors. It has been recently described that brain death results in a generalized derangement of basic functions ranging from tissue oxygenation to a systemic inflammatory reaction that leads to multi-organ dysfunction.
One possible source of organs and tissues for transplantation may come via the use of stem cells to generate transplantable tissues. A stem cell can (a) multiply, giving rise to a large progeny, and (b) differentiate into a number of tissues/organs, during the normal development of an organism.
Stem cells proliferate and then differentiate into all tissues and organs of the organism. We have begun to understand the intricate instructions that lead stem cell progenies to evolve to different fates, and there are initial proofs that these naturally occurring events can be recapitulated in vitro by providing the cells the proper cues.
For example, insulin-producing beta cells can be obtained from stem cells through use of growth factors and the precise delivery of signals (such as serum and insulin). These recent observations open exciting opportunities to identify complementary sources of transplantable tissue for humans. Using stem cells for organogenesis will face other hurdles, but remarkable progress has been made by combining stem cell therapies and techniques from the field of bioengineering. The first example of this progress, reported recently, was the "construction" of a bioengineered bladder, successfully implanted in patients with congenital bladder malformations.
While embryonic stem cells can produce all tissues and organs in an organism, there is increasing evidence that stem cells with more limited differentiation spectra also exist in neonatal and adult tissues. Blood from the umbilical cord can give rise to cells of different natures, such as pancreatic cells, cells of the nervous system, and bone and cartilage cells. Cells harvested from the bone marrow of adults also have been shown to preserve their "stemness" and can give rise to multiple tissues other than blood.
Stem cells therefore compose a remarkable evolving field of investigation for regenerative medicine. Stem cells can be used for the generation of bone marrow and mesenchimal cells that have been successfully utilized in tolerance-inducing protocols in animals.
The ultimate goal is to eliminate organ scarcity and patients time on a waiting list.
This research theme includes studies directed at optimizing organ and tissue use from human cadaveric donors, as well as aims focusing on the definition of complementary sources for human transplantation. In the first aim, we decipher the mechanisms that lead to functional impairment of human organs after donor death, organ harvesting and preservation, and inflammation in the immediate post-transplant period. In the second aim, we define complementary sources of transplantable tissues/organs derived from stem cells or non-human donors.
These areas of investigation synergize strongly with all efforts aimed at the induction of tolerance, since, for example, better organ preservation appears as a key requisite for success in tolerance-inducing protocols. Stem cells may not only provide the key to increasing organs for transplantation, but also to increase the availability of cells (bone marrow and mesenchimal) that are at the very core of tolerance induction protocols.
Recently, several studies have been made in tissue building. These include manufacturing a human bladder, which has subsequently been transplanted, as well as building cartilage and skin. There has also been successful reconstitution of a mouse heart using stem cells. There is good reason to believe this tolerance can be applied to large animals and humans to produce organs by utilizing a person's own cells. The major advantages in this case are that the cells are ready when needed and, because they are from the patient, there is no need for immunosuppression therapy.