Central Themes: Age-related differences; cell expansion and reconstitution; transplantation and cell fate; nonhuman primate models; in vivo imaging; feasibility and safety
Project 1 - Role of Endothelial Progenitors in Cord Blood Stem Cell Expansion
Clinical Importance: Human umbilical cord blood has been demonstrated to be an effective source of hematopoietic stem cells (HSC) for clinical transplantation, whether or not the host is a histocompatable match. A major limitation to more widespread use of this material is that the number of HSC in a cord blood sample may be insufficient to engraft, particularly with unrelated and mismatched recipients. Determination of a method to expand HSC in cord blood would be a major clinical advance for the field.
Project 2 - Role of Renal and Endothelial Progenitors in Fetal Kidney Reconstitution
Clinical Importance: This project is driven by the fact that the clinical condition of fetal urinary tract obstruction is one of the most important problems affecting young children with kidney disease. Reconstitution of fetal kidneys damaged by inherited diseases with stem and progenitor cells is necessary to restore the potential for form and function. These studies will provide the essential framework on which to embark upon potential intervention trials in the human fetus with lower urinary tract obstruction.
Project 3 - Transplant and Imaging of Human Stem and Progenitor Cells
Clinical Importance: These studies will focus on methods to expand human stem and progenitor cells prior to transplant and post-transplant using selection protocols, both of which could have significant clinical utility. The transplant of cells differentiated from human embryonic stem cells will address concerns related to the in vivo transplantation of these cells in humans. In addition, if imaging technologies with sufficient sensitivity to detect small quantities of cells can be developed, this would provide a very powerful tool for assessing the safety and efficiency of cell-based therapies in humans.