Stem Cell Differentiation for Myocardial Therapy

心肌治疗的干细胞分化

基本信息

项目摘要

DESCRIPTION (provided by applicant): Cell replacement therapy for damaged myocardium has been an important yet elusive goal in the treatment of heart failure. Our laboratory's overall goal is to understand the regulation of muscle cell proliferation and differentiation, and how such processes mediate myocardial development and disease. Our current approaches are to identify and characterize myocardial cells derived from human embryonic stem cells (hESCs), and to use these to both model myocardial development and explore cell therapies for myocardial diseases. Our goals for this proposal are to determine subpopulations of hESCs that develop into different cardiomyocyte types, identify the developmental stage at which hESC-derived myocardial cells most effectively engraft into host tissue, and demonstrate that hESC-derived cells can be used to improve cardiac function following myocardial injury. These relate directly to the long-range goal of PA-05-043 (Directed Stem Cell Differentiation for Cell-Based Therapies for Heart, Lung, And Blood, and Aging Diseases). The specific aims of this proposal are to: 1) identify specific subpopulations of proliferating hESCs that preferentially differentiate into cardiomyocytes; we will accomplish this by differentiating specific hESC subpopulations into cardiomyocytes in vitro, and characterizing developmental- and chamber-specific gene expression and action potential propagation; 2) determine the developmental stage at which hESC-derived myocardial cells most effectively engraft in vivo and the role of the tissue environment in cardiomyocyte subspecialization; we will accomplish this by developing reporter hESC lines and "molecular beacon" strategies for isolating myocardial cells at specific developmental time points, and determining their engraftment and differentiation in mouse myocardium in vivo; and 3) demonstrate the effects of cell therapy with hESC-derived myocardial cells in a mouse model of myocardial infarction; we will accomplish this by evaluating cardiac function and electrical conduction in a mouse model of myocardial infarction following transplant with hESC-derived myocardial cells. The proposed studies will provide new insight into human cardiac myogenesis, and offer novel approaches to myocardial regeneration.
描述(由申请人提供):针对受损心肌的细胞替代疗法一直是心力衰竭治疗中的一个重要但难以捉摸的目标。我们实验室的总体目标是了解肌细胞增殖和分化的调节,以及这些过程如何介导心肌发育和疾病。我们目前的方法是识别和表征源自人类胚胎干细胞(hESC)的心肌细胞,并利用它们来模拟心肌发育并探索心肌疾病的细胞疗法。我们此提案的目标是确定发育成不同心肌细胞类型的 hESC 亚群,确定 hESC 衍生的心肌细胞最有效地植入宿主组织的发育阶段,并证明 hESC 衍生的细胞可用于改善心肌损伤后的心脏功能。这些与 PA-05-043(针对心脏、肺、血液和衰老疾病的细胞疗法的定向干细胞分化)的长期目标直接相关。该提案的具体目标是:1)确定优先分化为心肌细胞的增殖 hESC 的特定亚群;我们将通过在体外将特定 hESC 亚群分化为心肌细胞,并表征发育和室特异性基因表达和动作电位传播来实现这一目标; 2) 确定 hESC 衍生的心肌细胞在体内最有效移植的发育阶段以及组织环境在心肌细胞亚特化中的作用;我们将通过开发报告 hESC 系和“分子信标”策略来实现这一目标,以在特定的发育时间点分离心肌细胞,并确定它们在体内小鼠心肌中的植入和分化; 3) 在小鼠心肌梗塞模型中证明 hESC 衍生心肌细胞的细胞治疗效果;我们将通过评估移植 hESC 来源的心肌细胞后的心肌梗塞小鼠模型的心脏功能和电传导来实现这一目标。拟议的研究将为人类心肌生成提供新的见解,并提供心肌再生的新方法。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Myocardial improvement with human embryonic stem cell-derived cardiomyocytes enriched by p38MAPK inhibition.
  • DOI:
    10.3109/14653249.2011.623690
  • 发表时间:
    2012-02
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
    Yeghiazarians Y;Gaur M;Zhang Y;Sievers RE;Ritner C;Prasad M;Boyle A;Bernstein HS
  • 通讯作者:
    Bernstein HS
The promise of human embryonic stem cells in aging-associated diseases.
  • DOI:
    10.18632/aging.100328
  • 发表时间:
    2011-05
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yabut O;Bernstein HS
  • 通讯作者:
    Bernstein HS
Labeling human embryonic stem cell-derived cardiomyocytes with indocyanine green for noninvasive tracking with optical imaging: an FDA-compatible alternative to firefly luciferase.
用吲哚菁绿标记人类胚胎干细胞衍生的心肌细胞,用于光学成像无创追踪:一种与 FDA 兼容的萤火虫荧光素酶替代品。
  • DOI:
    10.3727/096368909x478579
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Boddington,SophieE;Henning,TobiasD;Jha,Priyanka;Schlieve,ChristopherR;Mandrussow,Lydia;DeNardo,David;Bernstein,HaroldS;Ritner,Carissa;Golovko,Daniel;Lu,Ying;Zhao,Shoujun;Daldrup-Link,HeikeE
  • 通讯作者:
    Daldrup-Link,HeikeE
An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
  • DOI:
    10.1371/journal.pone.0016004
  • 发表时间:
    2011-01-04
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Ritner C;Wong SS;King FW;Mihardja SS;Liszewski W;Erle DJ;Lee RJ;Bernstein HS
  • 通讯作者:
    Bernstein HS
Subpopulations of human embryonic stem cells with distinct tissue-specific fates can be selected from pluripotent cultures.
  • DOI:
    10.1089/scd.2009.0012
  • 发表时间:
    2009-12
  • 期刊:
  • 影响因子:
    4
  • 作者:
    King FW;Ritner C;Liszewski W;Kwan HC;Pedersen A;Leavitt AD;Bernstein HS
  • 通讯作者:
    Bernstein HS
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HAROLD S BERNSTEIN其他文献

HAROLD S BERNSTEIN的其他文献

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{{ truncateString('HAROLD S BERNSTEIN', 18)}}的其他基金

PHOSPHORYLATION REGULATES HUMAN CDC5 FUNCTION
磷酸化调节人类 CDC5 功能
  • 批准号:
    7957368
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:
Stem Cell Differentiation for Myocardial Therapy
心肌治疗的干细胞分化
  • 批准号:
    7314264
  • 财政年份:
    2007
  • 资助金额:
    $ 19.31万
  • 项目类别:
STEM CELL ANTIGEN-1-INTERACTING PROTEINS
干细胞抗原 1 相互作用蛋白
  • 批准号:
    7180954
  • 财政年份:
    2005
  • 资助金额:
    $ 19.31万
  • 项目类别:
PHOSPHORYLATION REGULATES HUMAN CDC5 FUNCTION
磷酸化调节人类 CDC5 功能
  • 批准号:
    7180943
  • 财政年份:
    2005
  • 资助金额:
    $ 19.31万
  • 项目类别:
PHOSPHORYLATION REGULATES HUMAN CDC5 FUNCTION
磷酸化调节人类 CDC5 功能
  • 批准号:
    6976633
  • 财政年份:
    2004
  • 资助金额:
    $ 19.31万
  • 项目类别:
STEM CELL ANTIGEN-1-INTERACTING PROTEINS
干细胞抗原 1 相互作用蛋白
  • 批准号:
    6976645
  • 财政年份:
    2004
  • 资助金额:
    $ 19.31万
  • 项目类别:
CELL CYCLE REGULATION IN CARDIOVASCULAR BIOLOGY
心血管生物学中的细胞周期调节
  • 批准号:
    2806213
  • 财政年份:
    1999
  • 资助金额:
    $ 19.31万
  • 项目类别:
CELL CYCLE REGULATION IN CARDIOVASCULAR BIOLOGY
心血管生物学中的细胞周期调节
  • 批准号:
    6390248
  • 财政年份:
    1999
  • 资助金额:
    $ 19.31万
  • 项目类别:
CELL CYCLE REGULATION IN CARDIOVASCULAR BIOLOGY
心血管生物学中的细胞周期调节
  • 批准号:
    6537519
  • 财政年份:
    1999
  • 资助金额:
    $ 19.31万
  • 项目类别:
CELL CYCLE REGULATION IN CARDIOVASCULAR BIOLOGY
心血管生物学中的细胞周期调节
  • 批准号:
    6604668
  • 财政年份:
    1999
  • 资助金额:
    $ 19.31万
  • 项目类别:

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