CAREER: Production of Therapeutic T Cells from Mouse Embryonic Stem Cells: A Bioengineering Approach

该奖项的目标是开发有效的生物工程工具，将小鼠胚胎干细胞（ES）转化为造血祖细胞（HPCs），并最终转化为适合免疫治疗和移植的抗原特异性T细胞。特别是，3D支架结构和各种生物反应器培养对胚胎干细胞造血分化的影响将被研究。人工胸腺样环境将使用基于微珠的信号传导（合成胸腺基质细胞）和四聚体定向抗原呈递（人工抗原呈递细胞）来引导ES细胞衍生的HPCs进入功能性T细胞。研究目标，如果成功，将导致开发可扩展的方法产生造血干细胞和T细胞从胚胎干细胞。这可能最终为各种复杂的临床疾病，特别是癌症的治疗细胞的按需管理提供一个容易获得的来源。教育目标包括面向九年级和十年级学生的社区拓展项目，包括研究生和本科生生物医学工程专业的学生、德克萨斯大学的学习科学家以及地区高中的科学教师。PI还将通过让高中科学教师和学生参加的定期研讨会，开发基于人们如何学习（HPL）概念的以挑战为中心的教学模块。

Roy0547252The objective of this CAREER award is to develop efficient bioengineering tools to direct mouse embryonic stem (ES) cells to hematopoietic progenitor cells (HPCs) and ultimately to therapeutic, antigen-specific T cells suitable for immunotherapy and transplantation. In particular, the effects of 3D scaffold structures and various bioreactor cultures on hematopoietic differentiation of ES cells will be studied. Artificial thymus-like environments will be created using microbead-based signaling (synthetic thymic stromal cell) and tetramer-directed antigen presentation (artificial antigen presenting cell) to direct ES cell-derived HPCs into functional T cells. The research objectives, if successful, would lead to the development of scalable methods for generation of hematopoietic stem cells and T cells from ES cells. This could ultimately provide a readily available source for on demandadministration of therapeutic cells in a variety of complex clinical disorders, especially cancers. The educational objectives include community outreach programs for 9th and 10th graders, involving graduate and undergraduate biomedical engineering students and learning scientists from the University of Texas as well as science teachers from area high schools. The PI will also develop challenge-centered teaching modules based on how people learn (HPL) concepts through regular workshops involving high school science teachers and their students.