Artificial Accessory Cell Platform for Stem Cell Culture

描述(由申请者提供)：这个小型企业创新研究第一阶段项目将开发和展示一种广泛应用的人工辅助细胞原型，它可以用作细胞因子的补充和/或替代，用于定向将干细胞分化为所需的谱系。虽然这项技术适用于所有类型的干细胞，但对其生物学定位有一些信息，最初的技术演示和一系列产品将集中在造血干细胞(HSCs)上，因为这个经过充分研究的系统拥有广泛的知识和一系列细胞因子。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途径达到治疗目的是至关重要的。在体内，许多重要的细胞因子以膜结合或细胞外基质(ECM)结合的形式存在[1]。这种形式的呈现通常会在效应器细胞上诱导一种独特的生物反应，而这种反应是不能用可溶性分子形式复制的。此外，这一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，例如以体外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不同类型的底物的共价结合开发了许多替代化学，但该项目的重点是开发和验证一种稳定、一致和可商业化的微球系统，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.