PLATELET BIOGENESIS, INC — Department of Health and Human Services SBIR Phase II: NHLBI

Description

DESCRIPTION provided by applicant Platelet BioGenesis is developing a microfluidic bioreactor to produce human platelets at clinical scale Platelets are the andapos band aidsandapos of the bloodstream responsible for clot formation and blood vessel repair Low platelet count is a significant consequence of cancer treatment transplant and surgery for which platelets are a critical first line therapy to prevent mortality due to uncontrolled bleeding Platelet units comprising x platelets per mL are at present derived exclusively from human volunteer donors and must be stored at or above oC to avoid irreversible temperature related activation aggregation Risk of bacterial growth during room temperature storage limits shelf life to days of which are consumed by bacterial screening and by transport As a result blood centers typically do not have more than a day platelet inventory avail able for transfusion which is rapidly depleted in emergencies To address this major unmet need we have developed a platelet bioreactor that reproduces key features of adult bone marrow physiological microenvironment to trigger new platelet production at increasing scale To date we have shown that It is feasible to generate functional megakaryocytes and platelets from human induced pluripotent stem cells iP SCs a replenishable source of progenitor cells which can be stored frozen for years and our bioreactor will trigger platelet formation and improve the rate and extent of platelet production from human iPSC derived MKs above established static culture approaches This Direct to Phase II SBIR proposal outlines specific aims to determine quality safety and function of bioreactor derived platelets bdPLTs in humanized mouse models of thrombocytopenia and to scale platelet production to yield a human transfusion unit Aim Assess bdPLT quality storage profile and safety in vitro We will evaluate platelet structure biomarker expression metabolic activity and function under FDA approved storage conditions and determine their safety by enumerating residual leukocyte counts and assessing viral septic and teratoma risk Aim Assess the hemostatic and thrombogenic potential of bdPLT in humanized mice as well as platelet clearance and circulation time We will evaluate the in vivo behavior of bdPLTs in a novel murine model that permits human but not mouse platelet accrual at sites of arterial injury non GLP pilot study Hu man donor platelets will serve as a physiological control Aim Scale production fold to yield a human transfusion unit x bdPLTs per mL We will optimize our bioreactor design for continuous media perfusion and parallelization maximize megakaryocyte zonal distribution and trapping and equalize shear stress exposure throughout the device PUBLIC HEALTH RELEVANCE Human platelets are presently derived exclusively from volunteer donors and have a shelf life of days making platelet unit inventory sensitive to depletion and putting platelet recipients particularly immune compromised patients at risk of sepsis and viruses during surgery pregnancy and birth cancer HIV burn treatment and transplant There are currently no licensed therapeutics that immediately increases platelet counts and insufficient platelet supply to meet projected demand for necessary treatments M platelet units unmet demand in Platelet BioGenesis has developed a microfluidic bioreactor that mimics key physiological triggers of the bone marrow microenvironment to rapidly produce human platelets and seeks funding to scale it to the volumes needed for clinical use