Functional heart muscle regenerated in decellularized human hearts

News Brief by Dominic Kleinknecht

       Scientists at the Massachusetts General Hospital have made some initial steps towards creating new human hearts from donor heart scaffolds. In 2008, group leader Harald Ott developed a procedure to strip living cells from donor organs with a special detergent and repopulate the resulting cell-free organ scaffolds with corresponding cell types. Over the course of the following years, his team has used this method to create animal hearts, lungs, and kidneys, yielding the presented report that marks the first detailed analysis of both the remaining cardiac extracellular matrix scaffold after decellularization and recellularizing it.
         The study investigated a scaled-up version of Ott's method on 73 human hearts. They found that after the decellularization, the cardiac vasculature was neatly preserved and the extracellular matrix (non-cell tissue components) were highly retained while at the same time no traces of cardiac cells could be found. Most importantly, the decellularized heart showed an absence of human leukocyte antigens which are the main cause of organ rejection symptoms in transplantations. To repopulate this cell-free heart scaffold, the researchers used messenger RNA factors to reprogram skin cells into pluripotent stem cells and induced cardiac muscle cell differentiation. The cells passed crucial developmental genetic checkpoints and could be generated in sufficiently large quantities. These cells were then used to repopulate three different scaffolds: thin matrix slices, 15 mm matrix fibers (both yielded spontaneously contracting cardiac tissue formation ex-vivo) and whole decellularized human hearts. The whole hearts were treated in a special incubator mimicking physiological environmental stressors and providing a nutrient solution perfusion of the scaffold. The resulting tissue resembled immature cardiac tissue and contracted when externally stimulated.
        While this approach promises patient-specific disease treatment, therapies or organ regeneration, regenerating a whole heart is still years away. Hence, Ott's group will try to create cardiac 'patches' that could substitute damaged tissue in patients and aim to further improve their presented methods, which would constitute a major improvement in cardiac failure treatment.

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, Harald C. Ott. Bioengineering Human Myocardium on Native Extracellular  MatrixNovelty and Significance. Circulation Research, 2016; 118 (1): 56 DOI:  10.1161/CIRCRESAHA.115.306874