| 项目编号: | 1706155
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| 项目名称: | A high throughput platform for the selective generation of neurons from stem cells |
| 作者: | Ethan Lippmann
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| 承担单位: | Vanderbilt University
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| 批准年: | 2017
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| 开始日期: | 2017-07-01
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| 结束日期: | 2020-06-30
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| 资助金额: | 300000
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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: | cell type
; ipsc
; neuron
; differentiation condition
; pluripotent stem cell
; cell replacement therapy
; heterogeneous cell mixture
; da neuron
; high purity a9 midbrain da neuron
; project
; nashville public school system
; unique microformulator platform
; model system
|
| 英文摘要: | Human induced pluripotent stem cells (iPSCs) can grow indefinitely in culture and be specified to almost any cell type found in the human body. As such, they represent an attractive avenue for tissue engineering and cell replacement therapy. However, it remains difficult to convert iPSCs into sspecific cell types, which hinders their applications. This project uses a unique engineered device to simultaneously examine the effects of many different chemical cues on iPSC specification. The model system to be studied involves the generation of a subtype of neurons whose loss causes Parkinson's Disease (PD). Thus, the immediate outcomes of this project will have positive impacts on PD patients, and potential long-term implications for using iPSCs to replace other diseased tissues. The project will also support research experiences for undergraduates and for high school students through an existing outreach program with the Nashville public school system.
Human induced pluripotent stem cells (iPSCs) have the potential to revolutionize personalized medicine by serving as an unlimited source of patient-derived material for disease modeling, drug screening, and tissue engineering. A key challenge remaining is the reproducible differentiation of individual iPSC lines to homogeneous populations of the desired cell type. A majority of iPSC differentiation procedures yield heterogeneous cell mixtures, and differentiation conditions identified for one iPSC line often do not translate to other lines. Whereas in vivo development relies on diverse spatiotemporal cues, where subtle differences in growth factor concentrations can alter lineage trajectories, standard iPSC differentiation procedures utilize static cultures with infrequent media changes that lack continuous control over soluble protein and small molecule concentrations. As such, the objective of this proposal is utilize a unique microformulator platform, which permits independent media delivery to each well of a standard 96-well plate, for iPSC differentiations. The proposal's specific aims will be focused on producing A9 midbrain dopaminergic (DA) neurons, which are the cell type lost in Parkinson's Disease (PD). DA neurons have been previously differentiated from iPSCs but with heterogeneous identity and line-to-line variability. Thus, the utility and significance of the microformulator will be demonstrated by: 1) iterative screening of differentiation conditions that yield highly pure midbrain DA progenitors from a single iPSC line; 2) iterative screening of differentiation conditions that favor high purity A9 midbrain DA neurons over other DA subtypes; and 3) demonstration of rapid optimization of differentiation conditions to multiple iPSC lines. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/89765
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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: | |
Ethan Lippmann. A high throughput platform for the selective generation of neurons from stem cells. 2017-01-01.
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