| 项目编号: | 1351241
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| 项目名称: | CAREER: Biophysical Control of Cardiac Differentiation in Patient Specific Cardiac Stem Cells |
| 作者: | Lauren Black
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| 承担单位: | Tufts University
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| 批准年: | 2013
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| 开始日期: | 2014-04-15
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| 结束日期: | 2019-03-31
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| 资助金额: | USD431718
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| 资助来源: | US-NSF
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| 项目类别: | Continuing 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: | cardiac differentiation
; cell
; cpc
; cardiac muscle cell
; patient-specific
; differentiation
; functional differentiation
; pediatric patient
; patient-specific stem cell
; biophysical control
; major cell type
; differentiation protocol
; cardiac progenitor cell
; resident stem cell
; patient specific cardiac stem cellscurrent method
; stem cell
; differentiation pathway
; muscle cell endothelial cell
; cardiac extracellular matrix
; ckit
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| 英文摘要: | PI: Black, Lauren D.
Proposal Number: 1351241
Title: CAREER: Biophysical Control of Cardiac Differentiation in Patient Specific Cardiac Stem Cells
Current methods for deriving functional cardiac muscle cells from patient-specific stem cells have resulted in low efficiency in part because they only mimic the chemical signaling aspect of the environment of the cell present in the body. The studies described in this proposal seek to enhance our understanding of how patient-specific stem cells can be influenced to differentiate to cardiac muscle cells by understanding how the biophysical and biochemical environment external to the cells affects the ability of resident stem cells in the heart to turn into cardiac muscle. This work is particularly relevant because many of the current methods for differentiation of stem cells to cardiac muscle cells involve the use of growth factors and are highly inefficient. If successful, the proposed studies will be impactful in terms of advancing fundamental science, and for having significant potential in bringing medical applications closer to the clinic. Education and outreach activities are well integrated with the proposed research and involve local and inner city high schools as well as curriculum development for undergraduate and graduate students.
Recently, ckit+ cardiac progenitor cells (CPCs) have been singled out as one of the most promising sources of cells for cardiac repair because of their relative abundance, ease of isolation and their ability to differentiate into the three major cells types in the heart: smooth muscle cells endothelial cells and cardiomyocytes (CMs). The efficiency of differentiation of CPCs to functional CMs with standard soluble factor-based protocols has been low, but co-culture with native CMs or implantation in vivo have demonstrated an enhanced effect, indicating that other factors in the tissue microenvironment may be important for promoting cardiac differentiation of CPCs. The overall hypothesis of this proposal is that integrating substrate properties and bioelectric signaling will lead to enhancements in functional differentiation of pediatric patient derived CPCs. This hypothesis will be tested by: 1) establishing a baseline of cardiac differentiation of clonal populations of ckit+ CPCs derived from pediatric patients using growth factor or small molecule based differentiation protocols; 2) assessing the individual effects of substrate stiffness, substrate composition and resting membrane potential on cardiac differentiation of CPC clones and elucidate the specific mechanotransductive and differentiation pathways involved; and 3) determining the interactive effects of biophysical and bioelectric signaling in promoting the development of functional CMs from ckit+ CPCs. To carry out these aims, techniques previously developed in the PI's lab will be used to isolate/ characterize cardiac extracellular matrix, create substrates with different mechanical properties, and control resting membrane potential of cells. Functional differentiation of cells will be assessed via gene and protein expression, as well as calcium transient imaging and contraction force measurements via dynamic traction force microscopy. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/97072
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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: | |
Lauren Black. CAREER: Biophysical Control of Cardiac Differentiation in Patient Specific Cardiac Stem Cells. 2013-01-01.
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