权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Cellular Cardiomyoplasty in Vitro: Host-Donor Cell Interactions

体外细胞心肌成形术：宿主-供体细胞相互作用

基本信息

批准号：
7244031
负责人：
Nenad Bursac
金额：
$ 18.93万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-15 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7244031
关键词：
Affect Animal Experiments Arrhythmia Autologous Bone Marrow Bone Marrow Cells Calcium Cardiac Cardiac Myocytes Cardiomyoplasty Cell Communication Cell Transplants Cell membrane Cells Cicatrix Classification Clinical Coculture Techniques Complex Congenital Abnormality Coupling Cultured Cells Development Differentiation Inducer Evaluation Factor Analysis Future Gene Proteins Goals Growth Factor Heart Heart Injuries Implant In Vitro Infarction Ischemia Maps Mechanics Membrane Potentials Mesenchymal Stem Cells Methodology Microscopic Modeling Molecular Motion Myocardial Myofibroblast Numbers Optics Play Reporting Research Research Personnel Role Skeletal Myoblasts Staging Staining method Stains Stem cells Testing Tissues Up-Regulation Ventricular Remodeling base cell type design heart function implantation improved in vitro Assay injured intercellular communication programs repaired

项目摘要

DESCRIPTION (provided by applicant): Implantation of exogenous donor cells into the heart (cellular cardiomyoplasty) is an emerging methodology for the treatment of post-ischemic ventricular remodeling. While initial clinical implantations of autologous skeletal myoblasts and bone marrow cells have been promising, the intrinsic potential of these cells to affect electro-mechanical function of surrounding heart tissue has still not been elucidated. Therefore, the main goal of this proposal is to systematically study the ability of different donor cells (i.e. skeletal myoblasts and mesenchymal stem cells, as compared to control cardiac myofibroblasts) to propagate electro-mechanical activity through a host cardiac network in vitro. We hypothesize that: 1) propagation of electrical activity through donor cells depends on their type and stage of differentiation, as well as the presence of not only electrical but also mechanical junctions between the donor-donor and host-donor cell pairs, and 2) electro- mechanical propagation in the donor cell implant can be improved through upregulation of the intercellular communication by specific growth factors. To test these hypotheses we propose to study electrical conduction through donor cells using a geometrically simplified, reproducible one-dimensional setting, i.e. the micropatterned cardiomyocyte strands with inserts made of donor cells. The propagation of cell membrane potentials and intracellular calcium transients in donor cells will be optically mapped in the presence of various differentiation agents and growth factors. Obtained results will be correlated with those from immunohistochemical and molecular analyses. The findings from this proposal are expected to elucidate potential of different donor cells to functionally integrate in the heart. Eventually, the proposed experimental framework will allow us to perform high throughput in vitro analysis of the factors that can improve electromechanical propagation of different donor cells. The final aim is to aid in the development of efficient and safe cell-based approaches for the treatment of regional heart injury due to ischemia, infarction, or congenital defects.

描述（由申请方提供）：将外源性供体细胞植入心脏（细胞心肌成形术）是一种治疗缺血后心室重塑的新兴方法。虽然自体骨骼肌成肌细胞和骨髓细胞的初步临床应用已经很有希望，但这些细胞影响周围心脏组织的电机械功能的内在潜力仍然没有得到阐明。因此，本提案的主要目标是系统地研究不同供体细胞（即骨骼肌成肌细胞和间充质干细胞，与对照心脏肌成纤维细胞相比）通过体外宿主心脏网络传播电机械活动的能力。我们假设：1）电活性通过供体细胞的传播取决于它们的类型和分化阶段，以及供体-供体和宿主-供体细胞对之间不仅存在电连接而且存在机械连接，和2）供体细胞植入物中的机电传播可以通过特异性生长因子上调细胞间通讯来改善。为了验证这些假设，我们建议使用几何简化的、可再现的一维设置来研究通过供体细胞的电传导，即具有由供体细胞制成的插入物的微图案化心肌细胞链。供体细胞中细胞膜电位和细胞内钙瞬变的传播将在各种分化剂和生长因子的存在下进行光学映射。所得结果将与免疫组化和分子分析结果相关联。该提案的发现有望阐明不同供体细胞在心脏中功能整合的潜力。最终，所提出的实验框架将使我们能够进行高通量的体外分析的因素，可以提高不同的供体细胞的机电传播。最终目的是帮助开发有效和安全的基于细胞的方法，用于治疗局部心脏损伤，由于缺血，梗死或先天性缺陷。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Generation and customization of biosynthetic excitable tissues for electrophysiological studies and cell-based therapies.

用于电生理学研究和细胞疗法的生物合成兴奋组织的生成和定制。

DOI：
10.1038/nprot.2018.016
发表时间：
2018
期刊：
Nature protocols
影响因子：
14.8
作者：
Nguyen,HungX;Kirkton,RobertD;Bursac,Nenad
通讯作者：
Bursac,Nenad

Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

DOI：
10.1371/journal.pone.0011536
发表时间：
2010-07-12
期刊：
PloS one
影响因子：
3.7
作者：
Christoforou N;Oskouei BN;Esteso P;Hill CM;Zimmet JM;Bian W;Bursac N;Leong KW;Hare JM;Gearhart JD
通讯作者：
Gearhart JD

Stem cell therapies for heart disease: why do we need bioengineers?

心脏病的干细胞疗法：为什么我们需要生物工程师？