Artificial Accessory Cell Platform for Stem Cell Culture

描述（由申请人提供）：这个小型企业创新研究第一阶段项目将开发和展示一个广泛应用的人工辅助细胞原型，可作为细胞因子的补充和/或替代，用于干细胞定向分化为所需的谱系。虽然这项技术适用于所有类型的干细胞，但其生物利基的一些信息是可用的，但最初的技术演示和产品套件将集中在造血干细胞（hsc）上，因为造血干细胞系统具有广泛的知识和细胞因子范围。生物活性因子的固定化对于实现有效地引导干细胞沿着预期的治疗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[1]呈现。这种形式的呈现通常会在效应细胞上引起一种独特的生物反应，这种反应不能用分子的可溶性形式复制。此外，这种策略可能有效地限制大规模生产分化细胞所需的昂贵信号分子的数量，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为细胞因子与各种底物的共价结合开发了许多替代化学方法，但本项目的重点是开发和验证一种稳定、一致且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应用。

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.