Heart tissue
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Advances in Heart Tissue Engineering
Introduction to Cardiac Tissue Engineering
Cardiac tissue engineering is a rapidly evolving field aimed at developing functional heart tissues for therapeutic applications, disease modeling, and drug testing. The primary goal is to create engineered heart tissues (EHTs) that closely mimic the structure and function of native myocardium. This article synthesizes recent research advancements in the field, highlighting key methodologies and findings.
Engineered Heart Tissue (EHT) Constructs
Differentiation and Structural Properties
Recent studies have demonstrated the successful creation of EHTs using various cell sources and scaffolding materials. For instance, cardiac myocytes from neonatal rats, when combined with collagen I and subjected to mechanical stretch, form ring-shaped EHTs that exhibit characteristics of mature myocardium, including organized sarcomeres, gap junctions, and a well-developed T-tubular system. These constructs display contractile properties similar to native heart tissue, making them promising for in vitro studies and potential therapeutic applications.
Vascularization and Cell Survival
One of the significant challenges in cardiac tissue engineering is ensuring adequate vascularization to support cell survival and function. A study using human embryonic stem cells (hESCs) successfully created vascularized cardiac tissues containing endothelial cells and embryonic fibroblasts. These tissues demonstrated synchronous contraction and the presence of cardiac-specific molecular and functional properties, highlighting the importance of endothelial-cardiomyocyte interactions in promoting cell survival and proliferation.
3D Bioprinting and Functional Cardiac Tissues
Bioprinting Techniques
Three-dimensional (3D) bioprinting has emerged as a powerful technique for creating organized and scalable cardiac tissues. By using a fibrin-based bioink and primary cardiomyocytes, researchers have developed bioprinted cardiac constructs that exhibit spontaneous synchronous contraction and respond to cardiac drugs, indicating their potential for in vitro cardiac tissue development and maturation. This approach offers precise control over tissue architecture, which is crucial for replicating the complex structure of native myocardium.
Disease Modeling and Drug Testing
Combining human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with extracellular matrix (ECM) hydrogels has led to the creation of EHTs that can be used for disease modeling and drug testing. These constructs exhibit mature cardiac properties and can be used to study electrophysiological and calcium-handling characteristics, making them valuable for assessing drug-induced changes and modeling inherited cardiac disorders.
In Vivo Applications and Regenerative Medicine
Vascularized Tissue-Engineering Chambers
In vivo studies have shown the potential of using vascularized tissue-engineering chambers to create thick, beating cardiac tissues. By implanting neonatal rat cardiomyocytes in a Matrigel scaffold with an arteriovenous loop, researchers have generated vascularized cardiac tissues that contract spontaneously and exhibit typical cardiac muscle properties. This approach could pave the way for developing replacement tissues for heart defects.
Integration and Survival
Initial implantation studies using EHTs in animal models have demonstrated the survival and integration of these constructs in vivo. For example, collagen/matrigel-based cardiac muscle constructs have shown functional and morphological properties of differentiated heart muscle and have survived implantation in syngeneic rats. These findings suggest that EHTs could be a viable option for myocardial regeneration and repair.
Conclusion
Cardiac tissue engineering has made significant strides in developing functional heart tissues that mimic native myocardium. Advances in cell sourcing, scaffold materials, and bioprinting techniques have enabled the creation of EHTs with potential applications in disease modeling, drug testing, and regenerative medicine. Continued research and development in this field hold promise for addressing the challenges of heart disease and improving patient outcomes.
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