| 项目编号: | 1603524
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| 项目名称: | Identification and Characterization of Matrikines for Cardiac Differentiation and Regeneration |
| 作者: | Lauren Black
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| 承担单位: | Tufts University
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| 批准年: | 2016
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| 开始日期: | 2016-07-01
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| 结束日期: | 2019-06-30
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| 资助金额: | 424607
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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: | matrikine
; cecm
; cardiac differentiation
; stem cell
; proliferation
; cardiac regeneration
; identification
; treatment
; disease
; singular protein
; technique
; ecm
; cardiac injury
; ipsc-cm
; number
; investigator
; differentiation response
; hypothesis
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| 英文摘要: | PI: Black, Lauren D.
Proposal #: 1603524
There is great need for improved materials and techniques that can be used for the treatment of cardiac injury or disease. Investigators have shown that a variety of singular proteins derived from the cardiac extracellular matrix (cECM) promote cardiomyocyte (CM) proliferation or cardiac differentiation of stem cells, but little work has been done to identify the short peptide sequences on those proteins, termed matrikines, that are the active ingredients leading to the altered cellular responses. Based on preliminary data that indicates that cardiac cells respond differently to cECM obtained from fetal compared to adult hearts, the investigators of this 3 year project are going to test the hypothesis that there exists a number of matrikines in the developing heart ECM that could be useful in strategies for cardiac regeneration and repair, via enhancement of CM proliferation and survival and the cardiac differentiation of stem cells. Identification of these matrikines would be significant for understanding the importance of cECM remodeling during cardiac growth as well as for the potential development of therapeutics for the treatment of cardiac injury or disease. Educational impact will be made at the undergraduate and graduate levels through integration of techniques and results in courses and laboratories; impact at the high school level will be made through seminars at local high schools and as part of the Biomedical Engineering department's summer research program for high school students.
The composition of the extracellular matrix (ECM) is a powerful regulator of a number of cellular processes. In the heart, a variety of singular proteins derived from the cardiac ECM (cECM) promote cardiomyocyte (CM) proliferation or cardiac differentiation of stem cells. Most investigations to date have examined only singular ECM proteins as binding sites for the cells, even though the ECM in vivo is a complex mixture of proteins that is organ/ tissue and life stage specific. Furthermore, the emphasis has been on singular proteins rather than on the short peptide segments/matrkines that are likely to be the bioactive region leading to altered cellular responses. The investigators' lab has shown that cECM derived from fetal hearts promotes cardiomyocyte proliferation as compared to ECM derived from adult hearts and that cardiac progenitor cells have altered differentiation responses to cECM derived from different developmental stages. Thus, the goal of this project is to test the hypothesis that there exists a number of matrikines in the developing heart ECM that could be useful in strategies for cardiac regeneration and repair, via enhancement of CM proliferation and survival and the cardiac differentiation of stem cells. The hypothesis will be tested by carrying out two aims: 1) Identify and characterize matrikines derived from fetal and adult cECM (pigs at 3rd trimester and 3-6 months) that promote induced pluripotent stem cell (iPSC) differentiation to cardiac cells and/or enhance proliferation or maturation of iPSC-derived CMs (iPSC-CMs) and 2) Assess the efficacy of the matrikines derived from cECM in promoting human iPSC-CM survival, proliferation and function in 3-D engineered cardiac tissue models of healthy and diseased myocardium. Identification of these matrikines would be significant for understanding the importance of cECM remodeling during cardiac growth as well as for the potential development of therapeutics for the treatment of cardiac injury or disease. Educational impact will be made at the undergraduate and graduate levels through integration of techniques and results in courses and laboratories; impact at the high school level will be made through seminars at local high schools and as part of the BME department's summer research program for high school students. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/91963
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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: | |
Lauren Black. Identification and Characterization of Matrikines for Cardiac Differentiation and Regeneration. 2016-01-01.
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