SHOT proposes to perform research leading to the implementation of technology for the magnetic isolation of hematopoietic stem cells from human umbilical cord blood and peripheral apheresis product cells. Bone marrow transplantation (BMT) is an established therapy for certain types of leukemia and other hematologic diseases. The high cure potential of allogeneic BMT is limited by the requirement for closely-matched, histocompatible donors to minimize the possibility of graft-versus-host disease (GvHD). The ability to isolate stem cells opens a new clinical approach aimed at engineering a most suitable graft. SHOT's collaborators at The Cleveland Clinic Foundation have established that quadrupole magnetic flow sorting fulfills most of the requirements for successful hematologic stem cell selection. It is proposed to test this method owing to its much higher yield and capacity than most other methods. To do this requires an important research step, which fits well into the SBIR paradigm, namely the design of a disposable magnetic flow channel with sufficient precision and reproducibility to qualify ultimately for the isolation of human hematopoietic stem cells in the clinical setting. SHOT will (1) transfer existing magnetic flow channel technology from the Cleveland Clinic Foundation, (2) determine, through research, the optimum mass-production processes for high precision column manufacture, this process being ultimately eligible for cGMP qualification, and (3) test, through experimentation to be performed at The Cleveland Clinic, the efficacy of such columns. The proposed Phase I deliverable is a manufactured prototype flow channel tested in at least five experiments at The Cleveland Clinic. Phase II activities are expected to include integrating the manufacturable flow channels into a complete magnetic flow separator that SHOT will assemble into a pre-market prototype for continued laboratory research.
