Issue No. 2012
Imagine the Possibilities
Valerie Matthews Mehl
Date: December 20, 2011
Blood Cells Become Beating Heart Cells
With one look through the microscope, these cells are immediately and unquestionably identifiable. Though silent in this microscopic form, the rhythmic and continuing up and down motion causes the mind to think it hears the iconic thump thump--thump thump--thump thump of a beating heart. What appears beneath the lens of the microscope are single heart cells, no bigger than the tip of a needle, but as they beat, they are like tiny microcosms of the life-sustaining organ.
Watch a video of the beating heart cells
Still, more amazing than the cells themselves is the story of their origin. Days earlier they were human blood cells, like those that course through our veins and arteries, until researchers Elias Zambidis and Paul Burridge altered their destiny and transformed them into living, functioning heart cells. Now, instead of cells that are pumped out by the heart, they are part of the heart.
In a collaboration between the Kimmel Cancer Center, Institute for Cell Engineering, and Department of Biomedical Engineering, Zambidis, Burridge, and team successfully turned blood stem cells into functional, beating heart cells.
Their methodical two-year study, resulted in a simple, straight-forward recipe for changing blood stem cells into heart cells and called upon the expertise of basic scientists, stem cell engineers, and biomedical engineers. What they accomplished was previously considered impossible by international leaders in the field of regenerative medicine, and provided more evidence of the ingenuity, collaboration, and the relentless pursuit of answers that allow Johns Hopkins scientists to do what others cannot.
“Many scientists previously thought that a nonviral method like the one we used to induce blood cells to turn into highly functioning cardiac cells was not within reach, but we found a way to do it very efficiently,” says Zambidis.
For Zambidis, whose research interests are in pediatric oncology and cancers of the blood, the special “plasticity” of the blood stem cell that allows them to be transformed to a heart cell, holds important clues about how leukemia and other blood diseases develop and how they can be controlled. Burridge, who plans to specialize in cardiology, will focus his continued research on refining the technique in hope that, one day, a patient’s blood cells can be directly turned into heart cells to therapeutically repair hearts damaged by heart attack and other diseases.
To take cells from one source, in this case blood, and transform them into a heart or other cell type, scientists typically use viruses to deliver genes that will cause the cells to revert back to stem cells with open-slate potential to give rise to virtually any type of cell. Viruses, however, can mutate genes and initiate cancers in newly transformed cells. As a result, Zambidis, a cancer researcher, chose to use plasmids, rings of DNA that replicate briefly inside cells and eventually degrade, to deliver the genes.
To cause the actual transformation from one cell type to another, newly-reverted stem cells are placed in a controlled environment and bathed in a broth of growth factors and nutrients. The recipe for this “broth” varies from lab to lab and cell line to cell line, but Zambidis, Burridge and team created a universal recipe that, in their studies, worked consistently on nearly a dozen cell lines, and worked as well in transforming adult stem cells as it did in embryonic stem cells. To augment the cell transformation, the researchers created an oxygen-deprived environment that mimicked the natural human environment of these primitive cells.
Once transformed, the team set out to validate that the cells didn’t just look like heart cells but functioned like them as well. For this, they solicited the expertise of bioengineers, who developed and applied a miniversion of an electrocardiograph to the cells and proved that the cells were behaving like a normal human heart.
The discovery was only possible because Burridge was willing to do what scientists before him were not—his homework. For two years, he undertook the admittedly tedious job of combing through dozens of journal articles citing the varied techniques used to create cardiac cells. Next he made charts to analyze the wide range of techniques. Finally, after testing more than 100 combinations, Burridge was able to narrow the choices down to four to nine essential ingredients for each stage of cardiac development.
“We took the recipe for this process from a complex minestrone to a simple miso soup,” says Zambidis.
He cautions that the cells are not ready for human testing, but says the team continues to develop their methods, most recently turning blood cells into retinal, neural, and vascular cells. He is eager for other scientists to test the method in their own laboratories.