| 项目编号: | 1445650
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| 项目名称: | EAGER: Development-specific changes in ECM topography influence cardiac specification |
| 作者: | Brenda Ogle
|
| 承担单位: | University of Minnesota-Twin Cities
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| 批准年: | 2013
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| 开始日期: | 2014-07-15
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| 结束日期: | 2016-06-30
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| 资助金额: | USD106480
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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: | stem cell
; matrix
; cardiac cell type
; cell
; ecm protein
; cell-ecm interaction
; ecm architecture
; development-specific change
; ecm structure
; heart
|
| 英文摘要: | PI: Ogle, Brenda
Proposal Number: 1445650
Institution: University of Minnesota-Twin Cities
Title: EAGER: Development-specific changes in ECM topography influence cardiac specification
Stem cells have great potential to treat acute and chronic conditions, including cardiac disorders; however, the optimal methods of delivering these cells to patients have yet to be learned. Much of the difficulty lies in the disconnect between the tissue culture environments in which cells are typically grown, versus the complicated architecture of in vivo tissues. In the latter, tissues are encased in a network of nano and micoscale 3D fibers comprised of proteins such as collagen, laminin, and elastin that promote cell growth and synthesis of new tissue. This project aims to replicate the in vivo tissue structure, where the blueprint will be derived from microscopy data of cardiac tissues at various stages of development. Determining the stem cell response to the replicated tissue structure would have a significant and fundamental impact on how stem cells could be manipulated and delivered for both research and therapy. In addition, success of this proposal would have broad reaching utility for the study of cell-matrix interactions in other tissue types with health or disease.
A better understanding of stem cell-extracellular matrix (ECM) interactions could refine stem cell culture regimes and improve protocols to induce functional differentiation of cardiac cell types. Resultant differentiated cell types could be used for in vitro toxicity testing and to inform therapeutic delivery of stem cells or their progeny to the heart. It is hypothesized that 3D topographical features of the developing heart can guide differentiation of pluripotent stem cells or cardiac precursors into functional cardiac cell types. To test this hypothesis, methods to advance the differentiation and delivery of stem cells or their progeny will be developed by rigorous recapitulation of in vivo ECM architecture. Specifically multiphoton-excited (MPE) photochemistry will be used to create 3D matrices, one plane at a time, with sub-micron feature sizes, from templates derived from high resolution microscopy image data of the developing heart at well-defined timepoints. For this objective, matrices will be fabricated using BSA or methyl methacrylate to purposefully eliminate biochemical signals associated with ECM proteins (though it should be noted that the technology is capable of fabricating with ECM proteins). Ventricular progenitor cells (VPCs), capable of differentiating exclusively to mature cardiac cell types, will be seeded in the matrices. At weekly time points thereafter, cells in matrices will be tested for phenotypic and functional attributes of cardiac cell types. The primary comparator between matrices associated with developmental time points will be the percentage of cells with cardiomyocyte phenotype and function. The secondary comparator will be the relative percentage of each cardiac cell type. It is anticipated that a statistically significant increase in the percentage of functional cardiomyocytes will be detected in BSA or methacrylate-based structures derived from templates corresponding to late embryonic cardiac development relative to matrices corresponding to earlier and later time points. A successful stem cell response to ECM structure would have a significant and fundamental impact on how one can manipulate and deliver stem cells for both research and therapy, and would substantially impact research strategies for more generally understanding cell-ECM interactions in health and disease. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/96342
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Brenda Ogle. EAGER: Development-specific changes in ECM topography influence cardiac specification. 2013-01-01.
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