Deceased Donor Bone Marrow Salvage and Processing

ABSTRACT This program aims to develop a method for banking clinical grade bone marrow from cadaveric donors that can be deployed nationally to ameliorate shortages provide bone marrow stockpiles as medical countermeasures for nuclear threats and support existing research approaches such as delayed immune tolerance induction and transfusion of HIV resistant stem cells We will adapt a method designed by our research team for procurement processing and banking bone marrow from cadaveric vertebral bodies which has been shown to produce high yields of hematopoietic stem cells and other bone marrow cells from heart beating donors We have successfully transplanted bone marrow from these sources in clinical trials with no adverse patient reactions Now we aim to make key modifications to our method for deployment on a large scale creating a protocol whereby organ procurement organizations can routinely procure vertebral bodies from a large pool of donors and ship them successfully to a centralized facility for processing banking and post cryopreservation preparation for infusion This will create a large supply of bone marrow that can be used on demand off the shelf complementing existing bone marrow donor registries and cord blood banks The technical objectives of this Phase feasibility study are to develop a streamlined procurement protocol allowing organ procurement organizations to ship recovered vertebral bodies to a centralized processing facility test this optimized protocol for procurement from donors after cardiac death DCDs and non organ tissue donors and develop a protocol for washout of cryoprotectants at a centralized facility before shipment to clinics In Aim we will optimize and streamline the existing bone marrow collection and processing protocol for donors following brain death DBDs testing multiple preservation solutions for procurement and shipment of donor vertebral body bone marrow In Aim we will validate that the optimized protocol determined in Aim to can be applied to donors following cardiac death DCD and non organ tissue donors to determine the potential total donor pool In Aim we will optimize post cryopreservation processing to allow potential shipment of thawed large cell volume products to clinics after removal of all cryoprotective agents testing a hollow fiber dialysis filtration system that prevents loss of cell yield as cryoprotectants are removed The outcome of these aims will determine the most effective system for procurement processing and banking of cadaveric bone marrow for clinical use on a large scale NARRATIVE Shortages of bone marrow lead to thousands of deaths each year while waiting times worsen post transplant survival burdens which disproportionately affect ethnic minorities Additional sources of bone marrow and stem cell transplants are sorely needed to complement the existing living donor registry and cord blood banks We propose a method to bank clinical grade bone marrow from cadaveric donors which will ameliorate shortages provide bone marrow stockpiles as medical countermeasures for nuclear threats and support existing research approaches such as delayed immune tolerance induction and transfusion of HIV resistant stem cells