| 项目编号: | 1604677
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| 项目名称: | Biomimetic Materials to Elucidate the Role of Microenvironment in Glioblastoma Stem Cell Maintenance In Vitro |
| 作者: | Yonghyun Kim
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| 承担单位: | University of Alabama Tuscaloosa
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| 批准年: | 2016
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| 开始日期: | 2016-09-01
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| 结束日期: | 2019-08-31
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| 资助金额: | 425000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | role
; system
; microenvironmental influence
; glioblastoma stem cell
; cell
; gbm
; brain microenvironment
; microenvironmental signal
; glioblastoma multiforme
; gsc cell model
; year
; cell behavior
; established glioblastoma multiforme
; gsc phenotype
; high school student
; novel therapeutic evaluation system
; cell line
; native gsc microenvironment
; culture system
; proposed system
; biomimetic hyaluronic acid
; brain
; novel 3d culture system
; important role
; gsc
; 3d microenvironment
; cellular phenotype
|
| 英文摘要: | #1604677-Kim
This project focuses on developing and characterizing hyaluronic acid-based hydrogel 3D matrices as an in vitro test bed for studying glioblastoma stem cells (GSCs or brain tumor initiating cells), which play an important role in tumor formation and tumor recurrence in glioblastoma multiforme (GBM), one of the deadliest forms of human cancer. The matrices will be used to investigate the role of microenvironmental influences, particularly the role of mechanical and chemical signals on GSC phenotype and examine its utility in measuring therapy response. The system has the potential to provide a controllable and tunable environment closely mimicking the in vivo brain. The proposed system could lead to improved therapeutic options for patients (over 22,000/year) suffering from GBM. The system developed could be broadly utilized in understanding the role of microenvironmental signals in multiple types of cancer, particularly those that metastasize to the brain as well as in fundamental studies of neural development. Educational impact is achieved through development of an "Engineering Day" for high school students, providing research opportunities for under-represented female and African-American Students, integration of research related principles into existing courses and providing summer bioengineering workshops for high school students and teachers.
This project will combine biomaterials engineering strategies with current understanding of glioblastoma stem cell (GSC; also known as brain tumor initiating cell) biology to design a novel 3D culture system mimicking the native GSC microenvironment that would improve in vitro prediction of therapeutic response by allowing investigation of GSC-matrix interactions. GSCs cell models are superior to established glioblastoma multiforme (GBM) cell lines that are routinely employed in the drug development pipeline. GSCs freshly-derived from GBM patients are known to better recapitulate GBM biology. Though it is well-known that cell behavior is drastically altered when exposed to 3D microenvironments, GSCs are currently mainly cultured in artificial, 2D, and matrix-free environments (i.e., stiff tissue culture polystyrene) that do not appropriately capture the brain microenvironment. Furthermore, softer tissue-like biomaterials afford the ability to present the optimal combination of cues to provide more physiologically relevant environments, which can induce cellular phenotypes typically observed in vivo. For an improved fundamental understanding of microenvironmental influences on GSC phenotype, biomaterials mimicking the in vivo mechanical and chemical cues found in the brain microenvironment must be employed. In the planned studies, the investigators will use biomimetic hyaluronic acid (HA) hydrogels to establish the role of mechanical and chemical signals in maintenance of the GSC phenotype. Furthermore, they will utilize their culture system to quantify therapy response in vitro. Thus the main goal of the project is to create a novel enabling technology that will advance studies of GSC biology and aid future GBM drug development pipelines. GBM is among the deadliest forms of human cancer with an average survival of approximately one year. The proposed work is poised to provide a novel therapeutic evaluation system that can better predict clinical outcomes, thus could lead to improved therapeutic options affecting the lives of over 22,000 individuals per year. The system developed could be broadly utilized in understanding the role of microenvironmental signals in multiple types of cancer, particularly those that metastasize to the brain as well as in fundamental studies of neural development. Outreach activities include: 1) developing "Engineering Day" in high schools of rural Alabama's socioeconomically disadvantaged locality where the students are predominantly African-Americans, 2) providing engineering research opportunities to traditionally under-represented female and African-American students, 3) integrating various biology, materials science, and engineering principles into new and existing undergraduate and graduate level chemical engineering courses, and 4) providing annual summer bioengineering workshops for high school students and teachers. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/91015
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Yonghyun Kim. Biomimetic Materials to Elucidate the Role of Microenvironment in Glioblastoma Stem Cell Maintenance In Vitro. 2016-01-01.
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