The SmartBio System for the Improved Preservation of Human Hematopoietic Stem Cells

Abstract The ultimate goal of cryopreservationCPis to develop a biobanking process that results in a post thaw level of cell viability and function identical to a sister population that has not undergone preservationMost methods used for the clinical level CP of human hematopoietic stem cellshHSCsand related stem cellshoweverresult in poor recovery due to post thaw necrosis and apoptosis yielding an inferior cell product which is infused into patientsGiven that over half or more of all stem cell products in clinical trials todayincluding hHSCsare cryopreserved inDMSO which is highly toxicmany studies have investigated ways to improve CP as well as alternative cryoprotective agentsCPAssuch as sugar alcohols to avoid the known toxicity and impact of DMSO on hHSC differentiationYetto date no new hHSC CP process that eliminates DMSO has been developed commerciallyCPSI Biotech hypothesizes that multiple milestones must be achieved to generate the best possible hHSC CP process to yield optimal outcome for the stem cell patient while minimizing or eliminating the requirement for DMSOFirsta unique high throughput freezing device must be developed so that hHSC specific freezing profiles can be defined and executedSecondDMSO must be replaced with agents that can prevent the formation and re crystallization of lethal ice during the CP processThirda unique dry thaw system must be developed that will eliminate potential sample contaminationbe amenable to documentation and most importantly can provide for hHSC matched thaw profiles that can be achieved with a diverse array of biobanking vials and bagsFinallya post thaw recovery conditioning reagent and transfusion medium must be developed that can prevent post thaw delayed onset cell death and improve engraftment of hHSC during transplantThis Phase II program is designed to address each of these milestones under the following specific aimsSA aDevelop StemFreezea unique high throughput automated freezing system that has more operator and container flexibility than current systems such that hHSC matched freezing profiles can be developedSA bDevelop StemThawa derivative of the SmartThaw system supported by the parent Phase I project that will be expressly designed for optimizing the thawing process of hHSCs and other stem cells resulting in improved post thaw viability and functionSA aDevelop StemCPa non toxic CPA cryo cocktail containing Ice Recrystallization InhibitorsIRIsto replace DMSO which can be added to any carrier medium of choice to improve CP of hHSCs in the absence of DMSOSA bFormulate StemRevive and StemInfusiona first in class post thaw conditioning reagent and dilution media designed to ameliorate post thaw apoptosis necrosis increasing stem cell transfusion efficacy and SAEvaluate the stem cell specific SmartBio platform for optimized CP of HSCs in vitro and in vivoCollectively this multicomponent system will comprise a stem cell specific product line under CPSI s SmartBio platformIn summaryCPSI hypothesizes that addressing all five challenges together will streamline the biobanking process and move the hHSC CP sciences closer to the ultimate milestone of achieving a cryopreserved product that is equivalent to non frozen hHSCsThis achievement will result in improved outcome for patients receiving stem cell transplants This Phase II Application is designed to generate two new devicesStemFreezeStemThawthat can be used either in the clinic or in the research laboratory as well as three new solutionsStemCPStemReviveStemInfusionall of which when combined into CPSI s SmartBio platform will improve stem cell therapyThis will result in improved patient outcome for those individuals undergoing transplant of blood progenitor cells