Growing Human Hearts That Beat In The Lab

Scientists Grow Full-Sized, Beating Human Hearts from Stem Cells

It's the closest we've come to growing transplantable hearts in the lab

Alexandra Ossola | March 16, 2016

Of the 4,000 Americans waiting for heart transplants, only 2,500 will receive new hearts in the next year. Even for those lucky enough to get a transplant, the biggest risk is the their bodies will reject the new heart and launch a massive immune reaction against the foreign cells. To combat the problems of organ shortage and decrease the chance that a patient’s body will reject it, researchers have been working to create synthetic organs from patients’ own cells. Now a team of scientists from Massachusetts General Hospital and Harvard Medical School has gotten one step closer, using adult skin cells to regenerate functional human heart tissue, according to a study published recently in the journal Circulation Research.

Miniature, Beating Hearts Grown Using Stem Cells. Source: http://news.discovery.com/tech/biotechnology/miniature-beating-hearts-grown-using-stem-cells-150715.htm

<more at http://www.popsci.com/scientists-grow-transplantable-hearts-with-stem-cells; related links and articles: http://news.discovery.com/tech/biotechnology/miniature-beating-hearts-grown-using-stem-cells-150715.htm (Miniature, Beating Hearts Grown Using Stem Cells. July 15, 2015) and http://circres.ahajournals.org/content/118/1/56 (Bioengineering Human Myocardium on Native Extracellular Matrix. Jacques P. Guyette, Jonathan M. Charest, Robert W. Mills, Bernhard J. Jank, Philipp T. Moser, Sarah E. Gilpin, Joshua R. Gershlak, Tatsuya Okamoto, Gabriel Gonzalez, David J. Milan, Glenn R. Gaudette, and Harald C. Ott. Circulation Research. 2016; 118: 56-72. Published online before print October 26, 2015, doi: 10.1161/CIRCRESAHA.115.306874. [Abstract: Rationale: More than 25 million individuals have heart failure worldwide, with ≈4000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only ≈2500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective: The objective of this study is to translate previous work to human scale and clinically relevant cells for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human induced pluripotent stem cell–derived cardiomyocytes. Methods and Results: To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiomyocytes derived from nontransgenic human induced pluripotent stem cells and generated tissues of increasing 3-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole-heart scaffolds with human induced pluripotent stem cell–derived cardiomyocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions: Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human induced pluripotent stem cell–derived cardiomyocytes and enable the bioengineering of functional human myocardial-like tissue of multiple complexities.])>