There seems to be a trend developing around faster and cheaper means of producing human cells with therapeutic value from stem cells (post). In the newest research, cardiomyocytes, the workhorse cells that make up the beating heart, can now be made cheaply and abundantly in the laboratory.
The new technique transforms human stem cells — both embryonic and induced pluripotent stem cells — into these critical heart muscle cells by simple manipulation of one key developmental pathway. It promises a uniform, inexpensive and far more efficient alternative to the complex bath of serum or growth factors now used to nudge blank slate stem cells to become specialized heart cells.
"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," said Sean Palecek, University of Wisconsin-Madison professor of chemical and biological engineering.
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.
Researchers 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," said 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," says Xiaojun Lian, a UW-Madison graduate student. The beating cells made using the technique he devised have, so far, been maintained in culture in the lab for six months and remain as viable and stable as the day they were created.
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 just 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," said Kamp.
"The biggest advantage of our method is that it uses small molecule chemicals to regulate biological signals," said Palecek. "It is completely defined, and therefore more reproducible. And the small molecules are much less expensive than protein growth factors."
Adapted from the University of Wisconsin-Madison announcement.
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