Notch Mediated Expansion of Hematopoietic Precursors

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DESCRIPTION (provided by applicant): The goal of this R24 application is to establish a resource that will provide clinical grade reagents and methods for ex vivo expansion of human hematopoietic repopulating cells to improve cord blood transplantation. Umbilical cord blood has been established as an alternative source of stem cells for patients in need of stem cell transplantation who do not have an otherwise suitable donor identified. However, results have been limited due to inadequate stem cell numbers, leading to delayed engraftment that is often associated with lethal infection. Recently, our laboratory has developed novel methods, using Noth ligan, a known regulator of cell fate determination, to enhance the repopulating capacity of cord blood precursor cells. Thus, to extend these findings into the clinic and provide a resource for future clinical trials, we propose to optimize these methods for expanding cord blood precursor cells, and to develop cGMP compliant procedures methods and prepare the clinical grade reagents necessary for clinical trials. Successful completion of these aims will provide the basis for future efforts to establish the feasibility and safety of our approach in a phase I clinical trial, and then to provide the cGMP reagents and procedures as a resource for multi-institutional phase II and III trials.