Videos: Christopher Toepfer/Seidman lab
The human heart beats an estimated 2 to 3 billion times over a 70-year lifespan. Powering each beat are muscle cells’ individual units of contraction, called sarcomeres.
Above, sarcomeres beat in human heart cells in a lab dish.
The cells were made by turning back the developmental clock on adult skin cells and reprogramming them to become heart muscle cells, or cardiomyocytes.
A new technology from the lab of Christine and Jonathan Seidman in the Blavatnik Institute at Harvard Medical School tracks and measures the complex behavior of sarcomeres in these cells with much greater accuracy than has been possible before.
The tool, called SarcTrack—“a bad pun on Star Trek,” said Christopher Toepfer, a Sir Henry Wellcome postdoctoral fellow in the Seidman lab—allows researchers to study changes in sarcomere composition, beat rate and multiple contraction and relaxation properties caused by various diseases.
For instance, hypertrophic cardiomyopathy, a thickening of heart muscle that affects an estimated 1 in 500 people, causes heart cells to beat too hard and not relax enough between beats. This can lead to irregular heart rhythms, heart failure and sudden cardiac death.
Conversely, in dilated cardiomyopathy, an enlargement and thinning of the heart that affects an estimated 1 in 2,500 people, heart cells aren’t able to beat hard enough. The heart’s struggle to pump blood can cause heart failure, abnormal rhythms and problems with heart valves.
Scientists recently discovered how to edit the DNA of stem cell-derived heart cells so they contain the same mutations as in patients with these and other cardiovascular diseases.
Now researchers can use these cells rather than animal cells to study how sarcomere abnormalities arise from mutations, more quickly identify which mutations cause disease in patients where the source isn't clear and investigate drugs that might correct the problems.
The advance represents “the final frontier” in research efforts to understand and treat heart muscle diseases, said Toepfer.
Authorship and funding
SarcTrack was reported online Jan. 31 in Circulation Research. Toepfer and Arun Sharma, a research fellow in the Seidman lab, were co-first authors. Christine and Jonathan Seidman were co-senior authors.
Additional authors are affiliated with HMS, Brigham and Women's Hospital, Boston University, the Wyss Institute for Biologically Inspired Engineering, the Harvard Stem Cell Institute, the Max Delbrück Center for Molecular Medicine in Berlin, the German Centre for Cardiovascular Research in Berlin, Charité-Universitätsmedizin in Berlin, Hannover Medical School in Hannover, Germany, and Technische Universität München in Munich.
Support for this study was provided in part by the Fondation Leducq, the German Academic Scholarship Foundation, the Konrad Adenauer Foundation, the National Science Foundation (Engineering Research Centers Program, EEC-1647837) and the National Institutes of Health (grants 5R01HD085121, 5R01HL080494, 5R01HL084553 and U01HL098166). Christine Seidman is a Howard Hughes Medical Institute Investigator.
The Seidmans are founders of and own shares in MyoKardia Inc., a start-up developing therapeutics that target the sarcomere. MyoKardia was not involved in any aspect of the study.