Parth Patel receives TSF Resident Research Fellowship Award
FEBRUARY 2020
Parth M. Patel, MD, has been selected to receive a Thoracic Surgery Foundation (TSF) Resident Research Fellowship Award for his project entitled "Achieving tolerance in NHP heart transplant recipients with donor exosomes." Dr. Patel, an Emory integrated cardiothoracic surgery resident, is currently doing research at the Center of Transplantation Sciences (CTS) at Massachusetts General Hospital under the guidance of Joren C. Madsen, MD, DPhil, co-director of CTS and director of the MGH Transplant Center.
TSF Resident Research Fellowship Awards support the research endeavors of a resident who has not yet completed cardiothoracic surgical training. Although a specific research program is required as the major component of the application, recipients are primarily chosen based on their potential, their prior accomplishments, and the quality of their educational experiences. Additional criteria includes the probability of successful project completion and the potential significance of the particular educational effort toward the advancement of cardiothoracic surgery.
For his project, Dr. Patel intends to use bone marrow derived exosomes to induce cardiac allograft tolerance in non-human primates (NHPs). Exosomes are extracellular vesicles used by cells to communicate with each other.
Tolerance has been achieved in NHP and some human recipients of kidney allografts using a mixed chimerism approach in which the recipient undergoes an initial conditioning regimen and donor bone marrow transplantation. However, identical mixed chimerism protocols have historically failed to generate tolerance of heart allografts.
Dr. Madsen has induced tolerance of heart transplants in NHPs using a mixed chimerism protocol by co-transplanting a donor kidney—an organ known to be capable of producing immunological tolerance—with the heart, though transplanting a kidney simply to achieve heart allograft tolerance in humans is untenable, and bone marrow transplantation has its own inherent risks.
Dr. Patel proposes that substituting donor exosomes for donor bone marrow may allow for long-term survival and tolerance of isolated hearts without kidney and bone marrow co-transplantation, and could also avoid the risk of graft versus host disease. He hypothesizes that treatment of NHPs with donor exosomes could induce molecular chimerism (the harmonious coexistence of more than one genotype). This would create a more robust state of recipient tolerance than that achieved with donor bone marrow, resulting in long-term survival of heart allografts without immunosuppression, and could lead to a novel tolerance protocol that would improve outcomes in all organ transplant recipients.