Transplantation of allogeneic hematopoietic stem and progenitor cells (HSC) from umbilical cord blood (UCB) has been utilized to treat patients lacking traditional bone marrow (BM) donors. In both adult and pediatric recipients of unrelated UCB grafts, the major factor predicting successful outcomes (event-free survival, EFS) is cell dose transplanted. Previous work has shown that UCB HSC can be modestly expanded ex vivo in the closed automated AastromReplicell(TM) Cell Production System (ARS). The Phase I small-scale studies have shown that the addition of BM-derived stromal cells to UGB cultures significantly increased the number of HSC generated. In Phase II studies, the effects of culture variables (inoculum density, medium perfusion, cytokines) will be examined to further optimize HSC production, including NOD/scid repopulating cells, in the presence of stroma. Scale-up of the optimized UGB:stromal cultures will be validated in the ARS, and clinical trials are proposed to test the safety and efficacy of expanded HSG to augment standard UCB transplants. Phase III studies will continue to pursue clinical trials using optimally expanded UCB in stem cell transplants using either modified augmentation protocols or replacement strategies. Successful development and implementation of an improved expansion process will lead to greater clinical utility of UCB transplantation.
A closed automated, GMP system for ex vivo UCB cell expansion is of significant clinical and commercial value as a means of overcoming limiting cell dose in UCB transplants. Improving the UCB expansion process through the use of bone marrow stromal layers may result in increased clinical application of the AastromReplicell(TM) Cell Production System, as well as the generation of new protocols and kits to implement the improved process.
