Artificial Accessory Cell Platform for Stem Cell Culture

用于干细胞培养的人工辅助细胞平台

• 批准号: 8251861
• 负责人: TODD A MCADAMS
• 金额: $ 21.73万
• 依托单位: RESODYN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-10 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251861
• 关键词: Antigen-Presenting Cells; Antigens; Binding; Biological; Biological Assay; Biological Preservation; Blood Circulation; Caliber; Cell Culture System; Cell Culture Techniques; Cells; Chemistry; Clinic; Cytoskeleton; Development; EGF gene; Effector Cell; Employee Strikes; Equilibrium; Erythrocyte Transfusion; Excision; Goals; Growth; Growth Factor; Growth Factor Receptors; Hematopoietic stem cells; Immobilization; Individual; Knowledge; Length; Life; Membrane; Methods; Microspheres; Mono-S; Particle Size; Pathway interactions; Peptides; Perfusion; Phagocytosis; Phase; Polymers; Polystyrenes; Preservation Technique; Production; Proteins; Protocols documentation; Reagent; Reporting; Research Personnel; Scientist; Signal Transduction; Signaling Molecule; Small Business Innovation Research Grant; Stem cells; Surface; Suspension Culture; System; Technology; Testing; Therapeutic; Time; Variant; Vision; Work; base; cell growth; cell type; cost; cytokine; density; feeding; in vivo; interest; large scale production; practical application; prevent; programs; protocol development; prototype; receptor; response; scale up; small molecule; stem cell differentiation; stem cell therapy

DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project will develop and demonstrate a broad-application prototype Artificial Accessory Cell that can be used as a supplement and/or replacement for cytokines for the directed differentiation of stem cells into desired lineages. While the technology is applicable to all types of stem cells for which some information on its biological niche is available, the initial technology demonstration and suite of products will be focused on hematopoietic stem cells (HSCs) because of the extensive knowledge and range of cytokines available for this well-studied system. Immobilization of biologically active factors is essential to achieving the goal of efficiently directing stem cells along desired pathways for therapeutic aims. In vivo, many important cytokines are presented in membrane-bound, or extra-cellular matrix (ECM)- bound forms[1]. Presentation in this format often induces a unique biological response on the effectors cell that cannot be duplicated using soluble forms of the molecule. In addition, this strategy may be effective for limiting the quantity of expensive signaling molecules necessary for large-scale production of differentiated cells, such as the production of red blood cells for transfusion in an ex vivo format. While other investigators have developed much alternative chemistry for the covalent binding of cytokines to various types of substrates, the focus of this project is to develop and validate a stable, consistent, and commercializable microsphere-based system that can be applied as easily as soluble cytokines. PUBLIC HEALTH RELEVANCE: This Small Business Innovation Research Phase I project will develop and demonstrate the use of Artificial Accessory Cells (AACs) to help guide and control the differentiation of stem cells for therapeutic applications. In order to effectively scale-up and reduce the costs of bringing stem cell therapies to the clinic, more efficient means of providing the growth factors needed to guide stem cells are needed. Use of the proposed AACs has the potential to increase the efficacy and stability of these factors while reducing the costs for large-scale stem cell differentiation.

描述（由申请人提供）：该小型企业创新研究I期项目将开发和展示一种广泛应用的原型人工辅助细胞，可用作细胞因子的补充和/或替代，用于干细胞定向分化为所需谱系。虽然该技术适用于所有类型的干细胞，其中一些关于其生物学生态位的信息是可用的，但最初的技术演示和产品套件将集中在造血干细胞（HSC）上，因为广泛的知识和细胞因子的范围可用于这个经过充分研究的系统。生物活性因子的固定化对于实现有效地引导干细胞沿着用于治疗目的的所需途径的目标是必不可少的。在体内，许多重要的细胞因子以膜结合或细胞外基质（ECM）结合形式存在[1]。以这种形式呈现通常在效应细胞上诱导独特的生物学应答，其不能使用分子的可溶形式复制。此外，这种策略可以有效地限制分化细胞的大规模生产所需的昂贵信号分子的量，例如以离体形式生产用于输血的红细胞。虽然其他研究人员已经开发了许多替代化学方法用于细胞因子与各种类型的底物的共价结合，但该项目的重点是开发和验证一种稳定，一致和可商业化的基于微球的系统，该系统可以像可溶性细胞因子一样容易地应用。 公共卫生关系：这个小企业创新研究第一阶段项目将开发和展示人工辅助细胞（AAC）的使用，以帮助指导和控制干细胞的分化用于治疗应用。为了有效地扩大规模并降低将干细胞疗法引入临床的成本，需要更有效的手段来提供引导干细胞所需的生长因子。使用所提出的AAC有可能增加这些因子的功效和稳定性，同时降低大规模干细胞分化的成本。