A Novel Defined Xenobiotic Free Substrate that Mimics Natural Extracellular Matrix

一种模仿天然细胞外基质的新颖定义的无异生物质底物

基本信息

批准号：
8833107
负责人：
Jae-Sung Lee
金额：
$ 17.95万
依托单位：
PRIMORIGEN BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8833107
关键词：
AFP gene Address Adherent Culture Adhesions Albumins Amino Acid Sequence Animals Binding Biological Sciences Cardiac Myocytes Cell Adhesion Cell Culture Techniques Cell Differentiation process Cell Line Cell Lineage Cell Maintenance Cell Therapy Cell-Cell Adhesion Cells Clinical Complex Mixtures Cost Savings Cyclic GMP Degenerative Disorder Differentiation Antigens Disadvantaged Ectoderm Endoderm Endogenous Factors Ensure Evaluation Extracellular Matrix Extracellular Matrix Proteins Funding Germ Layers Goals Government Growth Factor Heparin Binding Hepatocyte Human Individual Karyotype Libraries Ligand Binding Ligands Maintenance Mesoderm Morphology Mus Output Peptides Performance Persons Phase Pluripotent Stem Cells Polystyrenes Preclinical Drug Evaluation Process Protocols documentation Regenerative Medicine Research Research Personnel Safety Small Business Innovation Research Grant Stem cells Surface Technology Testing Translations Work Xenobiotics abstracting cGMP production cell growth cost culture plates design induced pluripotent stem cell interest large scale production matrigel nerve stem cell nestin protein novel pathogen phase 1 study phase 2 study pluripotency public health relevance sarcoma self-renewal stage-specific embryonic antigen 4 stem cell therapy surface coating tissue culture

项目摘要

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 customers' unique needs.

描述（由申请人提供）：Primorigen Biosciences SBIR提案摘要Primorigen Biosciences将开发一个定义的，无Xenobiotic的合成细胞培养矩阵，该基质充分支持维护并指示人类诱导的多能干细胞（HIPSC）的分化，使所有三个细菌层（HIPSC）降低了所有三个细胞和巨大的干细胞成本的成本。当前，最常用的矩阵要么会产生重大的可靠性和安全性问题，要么仅在某些细胞系中有效，因为它们的CEL粘附机制有限。为了解决这些弊端，原始生成将开发出一种新的合成细胞培养矩阵，该基质通过呈现自然细胞外基质的关键属性，通过呈现多样化的合成配体，这些配体提供了多种机制，可为细胞粘附提供多种机制，并促进内源性因素的序列，从而减少了使用外来生长因素的需求和成本。第一阶段的研究将证明（a）创建合成细胞粘附和内源性因子隔离配体的库，（b）优化配体混合物在聚苯乙烯表面上的涂层条件，以及（c）验证新的合成细胞培养基质以维持HIPSC维护和指导性分化各种层次。 II期目标将通过扩展合成配体混合方法来验证其在大规模生产和HIPSC分化中的使用来建立这项工作。商业产量将包括（i）广泛适用的合成矩阵更换，由合成模块化配体的混合物组成，优化用于干细胞维持和分化的混合物，（ii）聚苯乙烯组织培养平台（例如，Petri Dish Dish Dish Dish Dish，Multiwell Plate和Microcarrier）与合成模块化模构模构成Ligant ligant ligand ligand ligant a，以及（III IIIII），以及（IIIII）。按订单进行，可以根据各个客户的独特需求来组装定制的混合物。