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

ECM Shrink Wrapped Human Cardiomyocytes and Endothelial Cells to Accelerate Myocardial Regeneration

ECM 收缩包裹人心肌细胞和内皮细胞以加速心肌再生

基本信息

批准号：
9924688
负责人：
Adam Walter Feinberg
金额：
$ 17.67万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9924688
关键词：
3-Dimensional Action Potentials Acute Address Alginates Animal Model Architecture Arrhythmia Autologous Basal lamina Biological Models Biomimetics Blood Vessels Calcium Caliber Cardiac Cardiac Myocytes Cardiovascular Diseases Cardiovascular system Cause of Death Cell Survival Cell Therapy Cell membrane Cell-Cell Adhesion Cells Cessation of life Chronic Clinical Treatment Collagen Collagen Type IV Confocal Microscopy Congestive Heart Failure Corneal Endothelium Coupling Cytoskeleton EFRAC Embryo Endothelial Cells Engineering Environment Event Extracellular Matrix Extracellular Matrix Proteins Eye Fibrin Fibroblasts Fibronectins Frequencies Future Gap Junctions Gel Gene Expression Goals Growth Growth Factor Heart Heart Diseases Heart Injuries Heart failure Human In Vitro Individual Injectable Injections Instruction Integrin Binding Laminin Mechanics Mitotic Morbidity - disease rate Muscle Muscle satellite cell Myocardial Myocardial Infarction Myocardium Nanostructures Natural regeneration Patients Performance Population Positioning Attribute Process Proliferating Proteins Risk Rodent Model Role Seminal Shapes Source Stroke Structure Surface Techniques Technology Therapeutic Thick Tissue Engineering Tissues Vascularization Work angiogenesis base cardiac regeneration cardiac repair clinical application clinically relevant cost density embryonic stem cell experimental study human embryonic stem cell improved in vitro Model in vivo in vivo regeneration induced pluripotent stem cell innovation matrigel mechanotransduction mortality multiphoton microscopy myogenesis nano nanoengineering nanofabrication nonhuman primate novel novel strategies paracrine regenerative therapy repaired scaffold stem stem cells tissue regeneration transdifferentiation

项目摘要

Myocardial infarction (MI) is a major cause of cardiac-related death in the US and those fortunate to survive the acute event suffer from chronic risk of arrhythmia, stroke and congestive heart failure. Repairing the heart is difficult because cardiomyocytes are post-mitotic and cannot proliferate in order to regenerate damaged tissue. Recent work has demonstrated that human cardiomyocytes can be derived from embryonic stem (ES) and induced pluripotent stem (iPS) cells, as well as transdifferentiated from other cells. However, survival and functional integration of these cardiomyocytes into stereotypical vascularized myocardium is still a major and unresolved challenge. This proposal describes a breakthrough towards therapeutic cell delivery by wrapping each cell in a nanostructured extracellular matrix (ECM) scaffold tailor made for enhancing survival, myogenesis and integration into infarcted myocardium. The key innovation in our approach is the ability to engineer 50-100 nm thick sheets of ECM with defined protein composition and shape and wrap this around individual cells or small cell ensembles. This is an improvement over current encapsulation technology because we can build the ECM around cardiomyocytes and endothelial cells to mimic the ECM that naturally surrounds these cells in the healthy heart. This is critical, because the ECM is a primary regulator of integrin binding, growth factor sequestration and mechanotransduction. Our preliminary results demonstrate that our novel surface-initiated assembly technique can build an ECM nano-scaffold from a range of matrix proteins and shrink wrap cardiomyocytes and endothelials cells. Further, we have shown using corneal endothelial cells that we can effectively delivery cells in vivo. This proposal will build upon these results by achieving three primary aims. One, develop the ECM nano-scaffold technology to shrink wrap cardiomyocytes and endothelial cells in engineered layers of fibronectin, laminin and collagen type IV that match the matrix in the native myocardium. Two, interrogate the role of ECM nano-scaffold composition, size and cell population on maximizing muscle formation, pre-vascularization and contractility in 3D tissue. Looking forward, achieving these aims will result in an injectable cell delivery technology that has enhanced capability to promote the retention, survival, integration, myogenesis and vascularization of cardiomyocytes and endothelial cells into the injured heart. This would have profound consequences by leading towards clinically-relevant therapeutic strategies to decrease morbidity and mortality in MI and cardiovascular disease patients

在美国，心肌梗死（MI）是导致心脏相关死亡的主要原因