PRIMORIGEN BIOSCIENCES INC. — Department of Health and Human Services SBIR Phase I: 200

Description

DESCRIPTION provided by applicant Primorigen Biosciences SBIR Proposal Abstract Primorigen Biosciences will develop a defined xenobiotic free synthetic cell culture matrix that fully supports maintenance and directed differentiation of human induced pluripotent stem cells hiPSCs down all three germ layers and dramatically reduces the costs of stem cell culture processes The current most commonly used matrices either create significant reliability and safety issues or are effective only with certain cell lines given their limited mechanisms for cel adhesion To address these drawbacks Primorigen will develop a new synthetic cell culture matrix that recapitulates key attributes of natural extracellular matrix by presenting diverse synthetic ligands that offer numerous mechanisms for cell adhesion and facilitate sequestration of endogenous factors thereby reducing the need for and costs of using exogenous growth factors Phase I studies will demonstrate feasibility by a creating a library of synthetic cell adhesion and endogenous factor sequestering ligands b optimizing the coating conditions of ligand mixtures onto polystyrene surfaces and c validating the new synthetic cell culture matrix for hiPSC maintenance and directed differentiation into various lineages Phase II objectives will build on this work by expanding the synthetic ligand mixture approach to validate their use in large scale production and differentiation of hiPSCs Commercial outputs will include i a broadly applicable synthetic Matrigel replacement comprised of synthetic modular ligand mixtures optimized for stem cell maintenance and differentiation ii polystyrene tissue culture platforms e g Petri dish multiwell plate and microcarrier pre coated with the synthetic modular ligand mixtures and iii a library of synthetic modular ligands from which made to order customized mixtures can be assembled according to individual customersandapos unique needs PUBLIC HEALTH RELEVANCE Primorigen Biosciences SBIR Proposal Narrative The self renewal and differentiation capacity of genetically stable human pluripotent stem cells create enormous potential for advancing drug screening and creating new cell therapies for a wide variety of tragic degenerative diseases Current protocols for maintenance and differentiation of pluripotent cells use undefined cell culture matrices of animal origin which present lot to lot variability and safety issues Defined xenobiotic free matrices have been developed that address these problems but their use is limited to fewer cell lines than observed with undefined matrices To address these combined shortcomings Primorigen will develop a synthetic defined xenobiotic free cell culture matrix from peptide mimics of several key ECM components and growth factors to provide multiple adhesion ligands to the cells and facilitate binding and temporal release of growth factors The resulting product will ensure broad applications across a wider diversity of cell lines and facilitate differentiation down all three grm layers while reducing the need for exogenous growth factors to drive down costs of stem cell culture processes The xenobiotic free attributes of the matrix will facilitate cell therapy applications and the substantial costs savings resulting from lower exogenous growth factor use will be compounded in cGMP production greatly increasing the affordability of new stem cell therapies