EAGER: Engineering of universally immunocompatible biological tissues using genetically modified embryonic stem cells and decellularized scaffolds

George Washington University, Washington DC

Investigators

Abstract

1231549/ Sarvazyan INTELLECTUAL MERIT. The proposed studies are at the intersection of different fields, including tissue bioengineering, cardiology, immunology, and tissue transplantation. The researchers propose to use an innovative approach to reduce rejection of embryonic stem cell (ESC)-derivatives by non-syngeneic hosts. The studies will use the latest stem cell differentiation techniques, molecular biology methods, and decellularized scaffold engineering. Projects will be executed by an interdisciplinary team of researchers with published expertise in the aforementioned fields. The creative and novel strategy of diminishing the expression of Major Histocompatibilty Complex Class I molecules and up-regulating Fas ligand expression is a practical and well-conceived plan that will help advance knowledge in developing universally immunocompatible tissues. The facilities and all required resources are fully available to the PI and her research team at the George Washington University to succeed in these studies. BROADER IMPACT. The researchers aim to develop new methods by which graft rejection can be suppressed. Their studies will contribute to the general understanding of how immunogenic molecules on the surface of undifferentiated and differentiated ESC can influence tissue transplantation. As a result of these studies minimally immunogenic ESC will be developed. The use of such cells in tissue engineering can help to reduce the need for aggressive immunosuppressive treatments. In the long term, this strategy can help to decrease the rates of morbidity and mortality associated with many degenerative diseases. This project assumes participation of junior faculty, undergraduate and graduate students, as well as high school students from the DC public school system. Throughout the years the PIs lab hosted and trained over 30 students. Their team was and continues to be very inclusive; they trained students of many faiths, different races and ethnical backgrounds, including many from underrepresented groups and minorities. Students involved in the proposed studies will be trained in the latest stem cell and molecular biology methods, as well as in scaffold-engineering protocols. Regeneration of tissues is one of the hottest topics in modern science, which is of high interest to the general public. The researchers plan to promote knowledge about the current state of research in this rapidly developing field through professional seminars, publications, and public lectures.