"Our protocol is more efficient and robust," explains Sean Palecek, the senior author of the report and a University of Wisconsin-Madison professor of chemical and biological engineering. "We have been able to reliably generate greater than 80 percent cardiomyocytes in the final population while other methods produce about 30 percent cardiomyocytes with high batch-to-batch variability."
The ability to make the key heart cells in abundance and in a precisely defined way is important because it shows the potential to make the production of large, uniform batches of cardiomyocytes routine, according to Palecek. The cells are in great demand for research, and increasingly for the high throughput screens used by the pharmaceutical industry to test drugs and potential drugs for toxic effects.
The capacity to make the heart cells using induced pluripotent stem cells, which can come from adult patients with diseased hearts, means scientists will be able to more readily model those diseases in the laboratory. Such cells contain the genetic profile of the patient, and so can be used to recreate the disease in the lab dish for study. Cardiomyocytes are difficult or impossible to obtain directly from the hearts of patients and, when obtained, survive only briefly in the lab.
Scientists also have high hopes that one day healthy lab-grown heart cells can be used to replace the cardiomyocytes that die as a result of heart disease, the leading cause of death in the United States.
"Many forms of heart disease are due to the loss or death of functioning cardiomyocytes, so strategies to replace heart cells in the diseased heart continue to be of interest," notes Timothy Kamp, another senior author of the new PNAS report and a professor of cardiology in the UW School of Medicine and Public Health. "For example, in a large heart attack up to 1 billion cardiomyocytes die. The heart has a limited ability to repair itself, so being able to supply large numbers of potentially patient-matched cardiomyocytes could help."
"These cells will have many applications,"
Lian and his colleagues found that manipulating a major signaling pathway known as Wnt — turning it on and off at prescribed points in time using two off-the-shelf small molecule chemicals — is enough to efficiently direct stem cell differentiation to cardiomyocytes.
"The fact that turning on and then off one master signaling pathway in the cells can orchestrate the complex developmental dance completely is a remarkable finding as there are many other signaling pathways and molecules involved," says Kamp.
"The biggest advantage of our method is that it uses small molecule chemicals to regulate biological signals," says Palecek. "It is completely defined, and therefore more reproducible. And the small molecules are much less expensive than protein growth factors."
According to Dennis Lox, MD, a sports, physical and regenerative medicine specialist in the Tampa Bay area, stem cells appear to hold great promise in treating a variety of diseases and conditions. Some conditions, such as joint, tendon and muscle injury, are treatable now with stem cells. Other conditions, such as ALS, diabetes, heart disease and MS, appear to be treatable with stem cell therapy, but widespread treatment is still in the near-future. Research into new ways of developing stem cells for any application adds greatly to the overall body of knowledge.
