Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease1-6. However, the predictive power of these models is presently limited by the immature state of the cells1, 2, 5, 6. Here we show that this fundamental limitation can be overcome if cardiac tissues are formed from early-stage iPSC-derived cardiomyocytes soon after the initiation of spontaneous contractions and are subjected to physical conditioning with increasing intensity over time. After only four weeks of culture, for all iPSC lines studied, such tissues displayed adult-like gene expression profiles, remarkably organized ultrastructure, physiological sarcomere length (2.2 µm) and density of mitochondria (30%), the presence of transverse tubules, oxidative metabolism, a positive force-frequency relationship and functional calcium handling. Electromechanical properties developed more slowly and did not achieve the stage of maturity seen in adult human myocardium. Tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, supporting the utility of this tissue model for studies of cardiac development and disease.The authors acknowledge funding support from the National Institutes of Health of the USA (NIBIB and NCATS grant EB17103 (G.V.-N.); NIBIB, NCATS, NIAMS, NIDCR and NIEHS grant EB025765 (G.V.-N.); NHLBI grants HL076485 (G.V.-N.) and HL138486 (M.Y.); Columbia University MD/PhD program (S.P.M., T.C.); University of Minho MD/PhD program (D.T.); Japan Society for the Promotion of Science fellowship (K.M.); and Columbia University Stem Cell Initiative (D.S., L.S., M.Y.). We thank S. Duncan and B. Conklin for providing human iPSCs, M.B. Bouchard for assistance with image and video analysis, and L. Cohen-Gould for transmission electron microscopy services.info:eu-repo/semantics/publishedVersio

Vascularization in Oral and Maxillofacial Tissue Engineering

This book provides a thorough, up-to-date description of the scientific basis and concepts of tissue engineering in the oral and maxillofacial region. The opening chapters present an introduction to tissue engineering, describe the roles of biomaterials and stem cells, discuss the use of growth factors, and examine potential adverse reactions. The challenges of soft and hard tissue engineering for oral and maxillofacial reconstruction are then considered in detail. It is explained what has been achieved to date, and potential future perspectives are explored. The importance and the verification of adequate vascularization are discussed, and a further focus is the use of 3D printing, both in the planning and production of scaffolds and in the bioprinting of cells and biomaterials. Information is also included on safety, efficacy, and regulatory aspects. Tissue Engineering in Oral and Maxillofacial Surgery will be of interest to all researchers and practitioners who wish to learn more about the potential of tissue engineering to revolutionize practice in oral and maxillofacial surgery