Microfluidic Cell Separation for Tissue Engineering and Regenerative Medicine

用于组织工程和再生医学的微流控细胞分离

• 批准号: 7882991
• 负责人: Shashi Murthy
• 金额: $ 66.87万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882991
• 关键词: 3-Dimensional; Adhesions; Adhesives; Adult; Affinity; Alginates; Area; Arts; Blood; Blood Vessels; Burn injury; Cardiac; Cardiac Myocytes; Cell Culture Techniques; Cell Separation; Cells; Characteristics; Clinical; Collaborations; Complex; Devices; Engineering; Equipment; Gel; Goals; Hair follicle structure; Harvest; Heart; Histocompatibility Testing; In Vitro; Intestines; Laboratories; Ligands; Methods; Microfluidic Microchips; Microfluidics; Mus; Muscle Cells; Natural regeneration; Play; Population; Rattus; Regenerative Medicine; Research; Role; Sales; Sampling; Sebaceous Glands; Site; Skin; Skin Tissue; Stem cells; Structure; Suspension substance; Suspensions; Sweat Glands; System; Techniques; Tissue Donors; Tissue Engineering; Tissues; Work; Wound Healing; base; cell type; cost; design; gastrointestinal; in vivo Model; novel; public health relevance; regenerative; repaired; scaffold; stem; tool

DESCRIPTION (provided by applicant): The major goal of this proposal is to create microfluidic cell separation systems to isolate or enrich key cell types for tissue engineering and regenerative medicine. In conventional tissue engineering, functional cell types must be enriched prior to seeding onto scaffolds. In cell-based approaches to tissue repair and regeneration, stem and progenitor cells resident in different tissue types must be isolated and characterized prior to their use. The design and fabrication of microfluidic cell separation systems for these applications is motivated by the following observations. First, in functional cell enrichment, microfluidic techniques are more systematic compared to state of the art methods such as pre-plating and using cell strainers. Second, microfluidic systems can handle small (microliter-order) sample volumes, enabling effective cell separation from small quantities of donor tissue. These systems can be incorporated with in-vitro cell culture equipment and furthermore, they are low-cost and easily operated on-site in clinical settings. Third, recent work in the PI's laboratory has demonstrated the ability of microfluidic devices to separate cell subpopulations based on size and affinity. This proposal will focus on the creation of microfluidic cell separation technologies for tissue engineering applications in four areas: cardiac tissue, skin, gastrointestinal tissue, and vascular tissue. The proposed work will be carried out in collaboration with experts in tissue engineering: Drs. Milica Radisic (cardiac), Rebecca Carrier (intestinal), Virna Sales & John Mayer (vascular), and Yaakov Nahmias & Martin Yarmush (skin/burns). During the 3-year project period, the following aims will be pursued along independent tracks: (1) design and fabricate size- and adhesion-based microfluidic separation devices to separate cell populations in cardiac and intestinal tissue; (2) design an adhesion-based microfluidic separation approach to isolate endothelial progenitor cells and skin stem cells by positive selection for regenerative applications; and (3) design an adhesion-based microfluidic separation approach to isolate cardiac progenitor cells and intestinal stem cells by negative selection. PUBLIC HEALTH RELEVANCE: The ability to grow sections of certain tissue types from a small sample of donor tissue, tissue engineering has grown tremendously in recent years. Recent work has also demonstrated how stem and progenitor cells resident in adult tissue can play a role in repairing tissue. A key component of either of these approaches is the requirement to isolate or harvest certain cell types prior to utilizing them for repair and regenerative applications and this proposal aims to create novel tools for this purpose.

描述（由申请人提供）：该提案的主要目标是创建微流体分离系统，以隔离或丰富组织工程和再生医学的关键细胞类型。在常规的组织工程中，必须在播种到支架上之前将功能性细胞类型富集。在基于细胞的组织修复和再生的方法中，必须在使用之前隔离和表征居住在不同组织类型中的茎和祖细胞。这些应用的微流体细胞分离系统的设计和制造是由以下观察结果激励的。首先，在功能性细胞富集中，与最先进的方法（例如预镀和使用细胞滤网）相比，微流体技术更有系统性。其次，微流体系统可以处理小（微级）样品体积，从而使有效的细胞与少量供体组织分离。这些系统可以与维特罗细胞培养设备合并，此外，它们是低成本且在临床环境中易于现场操作的。第三，PI实验室的最新工作证明了微流体设备根据大小和亲和力分离细胞亚群的能力。该建议将集中于在四个区域的组织工程应用中创建微流体细胞分离技术：心脏组织，皮肤，胃肠道组织和血管组织。拟议的工作将与组织工程专家合作进行：Drs。 Milica Radisic（心脏），Rebecca Carrier（肠道），Virna Sales＆John Mayer（血管）以及Yaakov Nahmias＆Martin Yarmush（Skin/Burns）。在三年的项目期间，将沿着独立的轨道追求以下目标：（1）设计和制造基于尺寸和粘附的微流体分离设备，以分离心脏和肠道组织中的细胞群体； （2）设计一种基于粘附的微流体分离方法，通过对再生应用的阳性选择来隔离内皮祖细胞和皮肤干细胞； （3）设计一种基于粘附的微流体分离方法，以通过阴性选择分离心脏祖细胞和肠干细胞。 公共卫生相关性：近年来组织工程从一小部分供体组织中种植某些组织类型的部分的能力。最近的工作还证明了居住在成人组织中的茎和祖细胞如何在修复组织中发挥作用。这两种方法中的任何一种的关键组成部分是在利用它们进行维修和再生应用之前隔离或收集某些细胞类型的要求，该建议旨在为此目的创建新颖的工具。