This application is a revised application in response to PA PA-01-128 (Pilot and Feasibility Program for Hematologic Diseases) inviting applications through the exploratory/developmental (R21) granting mechanism. The primary aim of this R21 application is to establish a murine model of in utero hematopoietic stem cell transplantation. We will be addressing homing and engraftment of adult hematopoietic stem cells within the fetal environment, which are specific research objectives of the program announcement. This model will also allow rapid testing of hypotheses that if correct can then further be studied in our non-human primate model of in utero transplantation. Success in the primate model would ultimately be necessary prior to clinical applications in the human fetus. A murine model will provide the setting where mutant and transgenic strains can be used to test specific factors that are likely to influence in utero hematopoietic transplantation. For this R21 proposal we plan to test the hypothesis that specific types of facilitating cells will improve in utero engraftment of adult hematopoietic stem cells. Future directions will be towards the use of this model to explore the role and function of developmentally regulated adhesion molecules and their receptors as they relate to fetal hematopoietic transplantation. ? ?
