Department of Pharmacology, University Medical Center Göttingen and Heart Research Center Göttingen, Germany.
Cells Tissues Organs. 2012;195(1-2):82-93. doi: 10.1159/000331407. Epub 2011 Oct 13.
Cardiac muscle engineering is evolving rapidly, aiming at the provision of innovative models for drug development and therapeutic myocardium. The progress in this field will depend crucially on the proper exploitation of stem cell technologies. Understanding the processes governing stem cell differentiation towards a desired phenotype and subsequent maturation in an organotypic manner will be key to ultimately providing realistic tissue models or therapeutics. Cardiogenesis is controlled by milieu factors that collectively constitute a so-called cardiogenic niche. The components of the cardiogenic niche are not yet fully defined but include paracrine factors and instructive extracellular matrix. Both are provided by supportive stromal cells under strict spatial and temporal control. Detailed knowledge on the exact composition and functionality of the dynamic cardiogenic niche during development will likely be instrumental to further advance cardiac muscle engineering. This review will discuss the concept of myocardial tissue engineering from the stem cell/developmental biology perspective and put forward the hypothesis of the cardiogenic niche as a fundamental building block of tissue-engineered myocardium.
心肌工程学正在迅速发展,旨在为药物开发和治疗性心肌提供创新模型。该领域的进展将取决于对干细胞技术的正确利用。理解控制干细胞向所需表型分化并随后以器官样方式成熟的过程将是最终提供现实组织模型或治疗方法的关键。心肌发生受微环境因素的控制,这些因素共同构成了所谓的心脏发生龛。心脏发生龛的组成部分尚未完全定义,但包括旁分泌因子和指导细胞外基质。两者均由支持性基质细胞在严格的时空控制下提供。在发育过程中,详细了解动态心脏发生龛的确切组成和功能可能有助于进一步推进心肌工程学。这篇综述将从干细胞/发育生物学的角度讨论心肌组织工程学的概念,并提出心脏发生龛作为组织工程化心肌的基本构建块的假说。