By combining tissue engineering techniques with human-induced pluripotent stem cell (hiPSC) technology, human-derived engineered cardiac tissues (ECTs) have been developed using several cell lineage compositions and 3-dimensional geometries. Although hiPSC ECTs are relatively immature compared with native adult heart tissues, they have promising potential as a platform technology for drug-screening and disease modeling, and as grafts for hiPSC-based regenerative heart therapy. This chapter provides the focused overview of the current status of cardiac tissue engineering technology and its possible application.

Stem Cells in Clinical Practice and Tissue Engineering is a concise book on applied methods of stem cell differentiation and optimization using tissue engineering methods. These methods offer immediate use in clinical regenerative medicine. The present volume will serve the purpose of applied stem cell differentiation optimization methods in clinical research projects, as well as be useful to relatively experienced stem cell scientists and clinicians who might wish to develop their stem cell clinical centers or research labs further. Chapters are arranged in the order of basic concepts of stem cell differentiation, clinical applications of pluripotent stem cells in skin, cardiac, bone, dental, obesity centers, followed by tissue engineering, new materials used, and overall evaluation with their permitted legal status.

Cardiac tissue engineering enables the generation of functional human cardiac tissue using cells in combination with biocompatible materials. Human pluripotent stem cell (hPSC)-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electrical pacing on the maturation of hPSC-derived cardiac tissues. In the first part of the study, cardiomyocytes derived from human induced pluripotent stem cells (hIPSCs) were used to generate collagen-based bioengineered human cardiac tissue. Engineered tissue constructs were subject to different stress and electrical pacing conditions. This engineered human myocardium exhibits Frank-Starling curve-type force-length relationships. After 2 weeks of static stress conditioning, the engineered myocardium demonstrated at least 10-fold increase in contractility and tensile stiffness, greater cell alignment, and a 1.5-fold increase in cell size and cell volume fraction within the constructs. Stress conditioning also increased sarco-endoplasmic reticulum calcium transport ATPase 2 (SERCA2) expression. When electrical pacing was combined with static stress conditioning, the tissues showed an additional 2-fold increase in force production, tensile stiffness, and contractility, with no change in cell alignment or cell size, suggesting maturation of excitation-contraction coupling. Supporting this notion, we found expression of RYR2 and SERCA2 further increased by combined static stress and electrical stimulation. These studies demonstrate that electrical pacing and mechanical stimulation promote both the structural and functional maturation of hiPSC-derived cardiac tissues. In the second part of the study, cardiovascular progenitor (CVP) cells derived from hPSC were used as the input cell population to generate engineered tissues. The effects of a 3-D microenvironment and mechanical stress on differentiation and maturation of human cardiovascular progenitors into myocardial tissue were evaluated. Compared to 2-D culture, the unstressed 3-D environment increased cardiomyocyte numbers and decreased smooth muscle numbers. Additionally, 3-D culture suppressed smooth muscle cell maturation. Mechanical stress conditioning further improved cardiomyocyte maturation. Cyclic stress-conditioning increased expression of several cardiac markers, like beta-myosin and cTnT, and the tissue showed enhanced force production. This 3-D system has facilitated understanding of the effect of mechanical stress on the differentiation and morphogenesis of distinct cardiovascular cell populations into organized, functional human cardiovascular tissues. In conclusion, we were able to create a complex engineered human cardiac tissue with both stem cell-derived cardiomyocytes and CVP cells. We showed that how environmental stimulations like mechanical stress, electrical pacing, and 3-D culturing can affect the maturation and specification of cells within the engineered cardiac tissues. The study paves our way to further apply these engineered cardiac tissues to other in vitro and in vivo usages like drug testing, clinical translation, and disease modeling.

This open access book focuses on the molecular mechanism of congenital heart disease and pulmonary hypertension, offering new insights into the development of pulmonary circulation and the ductus arteriosus. It describes in detail the molecular mechanisms involved in the development and morphogenesis of the heart, lungs and ductus arteriosus, covering a range of topics such as gene functions, growth factors, transcription factors and cellular interactions, as well as stem cell engineering technologies. The book also presents recent advances in our understanding of the molecular mechanism of lung development, pulmonary hypertension and molecular regulation of the ductus arteriosus. As such, it is an ideal resource for physicians, scientists and investigators interested in the latest findings on the origins of congenital heart disease and potential future therapies involving pulmonary circulation/hypertension and the ductus arteriosus.

​This book reviews the latest biotechnological advances with pluripotent stem cells, exploring their application in tissue engineering and medicinal chemistry. Chapters from expert contributors cover topics such as the production of transgene-free induced pluripotent stem cells (iPSCs), expansion, controlled differentiation and programming of pluripotent stem cells, and their genetic instability. Particular attention is given to the application of the pluripotent stem cells for vascularision of engineered tissue and for drug screening. This book will appeal to researchers working in regenerative medicine and drug discovery, and to bioengineers and professionals interested in stem cell research.

This book is a comprehensive and up-to-date resource on the use of regenerative medicine for the treatment of cardiovascular disease. It provides a much-needed review of the rapid development and evolution of bio-fabrication techniques to engineer cardiovascular tissues as well as their use in clinical settings. The book incorporates recent advances in the biology, biomaterial design, and manufacturing of bioengineered cardiovascular tissue with their clinical applications to bridge the basic sciences to current and future cardiovascular treatment. The book begins with an examination of state-of-the-art cellular, biomaterial, and macromolecular technologies for the repair and regeneration of diseased heart tissue. It discusses advances in nanotechnology and bioengineering of cardiac microtissues using acoustic assembly. Subsequent chapters explore the clinical applications and translational potential of current technologies such as cardiac patch-based treatments, cell-based regenerative therapies, and injectable hydrogels. The book examines how these methodologies are used to treat a variety of cardiovascular diseases including myocardial infarction, congenital heart disease, and ischemic heart injuries. Finally, the volume concludes with a summary of the most prominent challenges and perspectives on the field of cardiovascular tissue engineering and clinical cardiovascular regenerative medicine. Cardiovascular Regenerative Medicine is an essential resource for physicians, residents, fellows, and medical students in cardiology and cardiovascular regeneration as well as clinical and basic researchers in bioengineering, nanomaterial and technology, and cardiovascular biology.