Cardiac muscle cells derived from stem cells could eventually be used to treat heart diseases in children or adults, reshaping hearts with congenital defects or repairing damaged tissue.
Cardiomyocytes produced with the help of simulated microgravity. Red represents the cardiac muscle marker troponin, and green is cadherin, which helps cells stick to each other. Blue = cell nuclei. From Jha et al SciRep (2016).
Using the right growth factors and conditions, it is possible to direct pluripotent stem cells into becoming cardiac muscle cells, which form spheres that beat spontaneously. Researchers led by Chunhui Xu, PhD, director of the Cardiomyocyte Stem Cell Laboratory in Emory’s Department of Pediatrics, are figuring out how to grow lots of these muscle cells and keep them healthy and adaptable.
As part of this effort, Xu and her team discovered that growing stem cells under “simulated microgravity” for a few days stimulates the production of cardiac muscle cells, several times more effectively than regular conditions. The results were published on Friday, Aug. 5 in Scientific Reports. The first author of the paper is postdoctoral fellow Rajneesh Jha, PhD.
Xu and her lab are in the Children’s Heart Research and Outcomes Center, part of the Emory-Children’s-Georgia Tech Pediatric Research Alliance. Xu is also part of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. Co-authors include Hee Cheol Cho, PhD, Hanjoong Jo, PhD, Kevin Maher, MD and Mary Wagner, PhD.
Most mammalian or human cells that researchers culture in the laboratory grow on plastic plates. That means gravity is pulling on and flattening the cells constantly. To cancel out the effects of gravity, scientists could send their cells on rockets into Earth orbit. But that could get expensive, and expose cells to even stronger acceleration. Instead, scientists use a device called a “random positioning machine.” It rotates cells so that they don’t get used to gravity being applied in one direction.
Random positioning machine in operation. Photos courtesy of Rajneesh Jha.
A stream of recent research probes the effects of simulated microgravity on cells, both to model what it would be like in space, and to assess whether it can help to grow cells under conditions that are more like being part of an three-dimensional organ.
Jha and colleagues keep the period of microgravity short – just three days – and note that exposing stem cells to microgravity for longer times (two weeks) was previously shown to inhibit their differentiation.
“This culture system increases proliferation and viability of cardiac progenitors, which could improve the application of these cells in regenerative medicine,” they write.
The use of stem-cell-derived cardiac muscle cells to treat heart disease is still experimental, but looks like it is getting closer. Encouraging results have been observed in non-human primates and a clinical trial is underway in France.
In their experiments, the Emory researchers used both induced pluripotent stem cells, generated from lung cells, and human embryonic stem cells, originally derived by Thomson and colleagues in the 1990s and approved for research by the National Institutes of Health.
The research was supported by the Center for the Advancement of Science in Space (GA-2014-126) and the National Heart Lung and Blood Institute (R21HL118454).
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