- Dr. Nicholas Zavazava, Principal Investigator
- Sabrina Bonde, Research Associate
- Kerstin Brotzmann, Research Associate
- University of Iowa Health Care, Iowa City, USA
- Application of Embryonic Stem Cells to Avoid Rejection of Transplanted Organs
Organ transplantation has been ongoing now for some 50 years. However, despite improvement in immunosuppression, more than 50% of the organs are lost within 10 years. These poor results re-enforce the need for establishing tolerance models that will in the future prevent or drastically reduce organ loss.
Here, we propose to study mouse embryonic stem cells and their efficacy to prevent organ rejection. Our hypothesis is that embryonic stem cells are tolerated by recipient animals due to their low immunogenicity. Once stable mixed chimerism has been achieved, we anticipate that transplantation of organs will subsequently be successful. We will use skin grafting as a model and study the mechanisms by which embryonic stem cells induce a state of mixed chimerism. For example, we plan to examine whether FasL, naturally expressed by embryonic stem cells, is a requirement for the engraftment of embryonic stem cells. The lpr/lpr mouse that expresses a Fas mutant molecule will be used for these studies. Achievement of tolerance by the use of embryonic stem cells will facilitate their practical application in clinical medicine and biomedicine overall. The data obtained here will not only be useful and critical in organ transplantation, but also in the use of embryonic stem cells in the treatment of autoimmune and degenerative diseases.