BRIGE: Engineering a BioMatrix Library Derived from Induced Pluripotent Stem Cells

BRIGE：工程化源自诱导多能干细胞的 BioMatrix 文库

• 批准号: 1342192
• 负责人: Yan Li
• 金额: $ 17.47万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1342192&HistoricalAwards=false
• 关键词: BRIGE; Engineering; BioMatrix; Library; Derived

Technical Description:Human Induced Pluripotent Stem Cells (hiPSC) are adult cells (for example, skin cells derived from a biopsy) that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. They have great potential for drug screening, disease modeling, and eventually cell therapy for humans. Induced pluripotent stem cells (iPSCs) have great potential to understand diseases and develop therapeutics. Current matrices that are used for iPSC self-renewal and differentiation fail to recapitulate the complex signaling network during lineage specification. To address this issue, a novel Biomatrix Library will be generated in the proposed research to study the complex signaling during stem cell development. The unique feature of the proposed Biomatrix Library is the maintenance of the broad signaling capacity and preservation of signaling network during tissue development and morphogenesis. The specific tasks in the proposed study include: 1) generation and high-content characterization of a Biomatrix Library with various biochemical and biological properties; 2) high-throughput screening and validation of the Biomatrix Library for self-renewal and neural differentiation of iPSCs. The Biomatrix-based functional neural differentiation will be translated into a bioreactor to confirm the predicative effect from the screening. The long-term objective of this research is to obtain comprehensive understanding of cell-biomatrix interactions in regulating lineage-specific differentiation of iPSCs.Broader Significance and Importance:Induced pluripotent stem cells that are artificially derived from adult cells (e.g., skin cells) provide an alternative to embryonic stem cells for research. This 2012 Nobel Prize winning discovery represents an important advance in scientific research as they allow researchers to obtain pluripotent stem cells, which have the ability to become any cell type in the body, without the controversial use of embryos. Using well-established iPSC cell lines, the proposed study will identify the key interactions of cells, matrices and growth factors that could regulate cell fate decision. The research outcome will guide the biomimetic material design and the large scale generation of functional tissue cells for drug screening, disease modeling, and eventually cell therapy. This proposal details a transformative research plan to achieve highly efficient differentiation of iPSCs, regulated by the engineered Biomatrix that will be identified through innovative high content characterization, high-throughput screening, and functional analysis. The gained knowledge can be directly transformed to technology commercialization in the biopharmaceutical and biotechnology industries. Broadening Participation of Underrepresented Groups in EngineeringThe target populations of broadening participation activities in the proposed efforts include the African-American, Hispanic, and women students in Florida A&M University, a historically black college, Florida State University, a major research university with a large female enrollment, and Tallahassee community. Globally, the PI will provide mentoring and leadership training for Turkish women students using Global Educational Outreach in Science, Engineering and Technology portal. The PI will incorporate the skills required in industry such as current Good Manufacturing Practices and Quality by Design in the curriculum. These activities will bridge the gap between education and application, and also attract the students from under-represented groups to stay in science and engineering. The results from the proposed research and education efforts will be disseminated to K-12 students in Leon County School District and in Challenger Learning Center, to undergraduates in Biomedical Engineering Society, and to students in National Society of Black Engineers. In particular, the mentoring activities will broaden the participation of women in science and engineering locally and globally, especially in Tallahassee and Turkey.This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.

技术描述：人类诱导多能干细胞 (hiPSC) 是成体细胞（例如，来自活组织检查的皮肤细胞），通过被迫表达对维持多能干细胞重要的基因和因子，已被基因重编程为胚胎干细胞样状态。定义胚胎干细胞的特性。 它们在药物筛选、疾病建模以及最终的人类细胞治疗方面具有巨大的潜力。诱导多能干细胞 (iPSC) 在了解疾病和开发治疗方法方面具有巨大潜力。 当前用于 iPSC 自我更新和分化的基质无法概括谱系规范过程中的复杂信号网络。 为了解决这个问题，在拟议的研究中将生成一个新的生物基质库，以研究干细胞发育过程中的复杂信号传导。 所提出的生物基质库的独特之处在于在组织发育和形态发生过程中维持广泛的信号传导能力并保存信号网络。 本研究的具体任务包括：1）具有各种生化和生物特性的生物基质库的生成和高内涵表征； 2) 对 iPSC 自我更新和神经分化的 Biomatrix 库进行高通量筛选和验证。 基于生物基质的功能性神经分化将被转化为生物反应器，以确认筛选的预测效果。 这项研究的长期目标是全面了解细胞-生物基质相互作用在调节 iPSC 谱系特异性分化方面的作用。更广泛的意义和重要性：人工衍生自成体细胞（例如皮肤细胞）的诱导多能干细胞提供用于研究的胚胎干细胞的替代品。 这项荣获 2012 年诺贝尔奖的发现代表了科学研究的一项重要进步，因为它们使研究人员能够获得多能干细胞，这种干细胞有能力成为体内的任何细胞类型，而无需使用有争议的胚胎。 使用成熟的 iPSC 细胞系，拟议的研究将确定细胞、基质和生长因子之间可以调节细胞命运决定的关键相互作用。 研究成果将指导仿生材料设计和功能组织细胞的大规模生成，用于药物筛选、疾病建模和最终的细胞治疗。 该提案详细介绍了一项变革性研究计划，以实现 iPSC 的高效分化，由工程化生物基质调节，该生物基质将通过创新的高内涵表征、高通量筛选和功能分析进行鉴定。 所获得的知识可以直接转化为生物制药和生物技术行业的技术商业化。 扩大工程领域代表性不足群体的参与拟议工作中扩大参与活动的目标人群包括佛罗里达农工大学（一所历史悠久的黑人学院）的非裔美国人、西班牙裔学生和女学生、佛罗里达州立大学（一所拥有大量女性学生的主要研究型大学）招生和塔拉哈西社区。 在全球范围内，PI 将利用科学、工程和技术领域的全球教育外展门户为土耳其女学生提供指导和领导力培训。 PI 将在课程中纳入行业所需的技能，例如当前的良好制造规范和质量源于设计。 这些活动将弥合教育和应用之间的差距，并吸引弱势群体的学生留在科学和工程领域。 拟议的研究和教育工作的结果将传播给莱昂县学区和挑战者学习中心的 K-12 学生、生物医学工程学会的本科生以及国家黑人工程师协会的学生。 特别是，指导活动将扩大女性在本地和全球科学和工程领域的参与，特别是在塔拉哈西和土耳其。这项研究是通过工程征集扩大参与研究启动赠款资助的，该赠款是扩大参与工程的一部分工程教育和中心部门的工程计划。