Writing this week (May 28, 2012) in the Proceedings of the National Academy of Sciences , a team of Wisconsin scientists describes a way to transform humanstem cells — both embryonic and induced pluripotent stem cells –into the critical heart muscle cells by simple manipulation of onekey developmental pathway. The technique promises a uniform,inexpensive and far more efficient alternative to the complex bathof serum or growth factors now used to nudge blank slate stem cellsto become specialized heart cells. “Our protocol is more efficient and robust,” explainsSean Palecek, the senior author of the new report and a Universityof Wisconsin-Madison professor of chemical and biologicalengineering. “We have been able to reliably generate greaterthan 80 percent cardiomyocytes in the final population while othermethods produce about 30 percent cardiomyocytes with highbatch-to-batch variability.” The ability to make the key heart cells in abundance and in aprecisely defined way is important because it shows the potentialto make the production of large, uniform batches of cardiomyocytesroutine, according to Palecek. The cells are in great demand forresearch, and increasingly for the high throughput screens used bythe pharmaceutical industry to test drugs and potential drugs fortoxic effects. Smart Car Turbocharger
The capacity to make the heart cells using induced pluripotent stemcells, which can come from adult patients with diseased hearts,means scientists will be able to more readily model those diseasesin the laboratory. Such cells contain the genetic profile of thepatient, and so can be used to recreate the disease in the lab dishfor study. Cardiomyocytes are difficult or impossible to obtaindirectly from the hearts of patients and, when obtained, surviveonly briefly in the lab. Scientists also have high hopes that one day healthy lab-grownheart cells can be used to replace the cardiomyocytes that die as aresult of heart disease, the leading cause of death in the UnitedStates. China Mitsubishi Turbo Kits
“Many forms of heart disease are due to the loss or death offunctioning cardiomyocytes, so strategies to replace heart cells inthe diseased heart continue to be of interest,” notes TimothyKamp, another senior author of the new PNAS report and a professor of cardiology in the UW School of Medicineand Public Health. “For example, in a large heart attack up to1 billion cardiomyocytes die. The heart has a limited ability torepair itself, so being able to supply large numbers of potentiallypatient-matched cardiomyocytes could help.” “These cells will have many applications,” says XiaojunLian, a UW-Madison graduate student and the lead author of the newstudy. The beating cells made using the technique he devised have,so far, been maintained in culture in the lab for six months andremain as viable and stable as the day they were created. Turbocharger Repair Kit
Lian and his colleagues found that manipulating a major signalingpathway known as Wnt — turning it on and off at prescribed pointsin time using just two off-the-shelf small molecule chemicals — isenough to efficiently direct stem cell differentiation tocardiomyocytes. “The fact that turning on and then off one master signalingpathway in the cells can orchestrate the complex developmentaldance completely is a remarkable finding as there are many othersignaling pathways and molecules involved,” says Kamp. “The biggest advantage of our method is that it uses smallmolecule chemicals to regulate biological signals,” saysPalecek. “It is completely defined, and therefore morereproducible.
And the small molecules are much less expensive thanprotein growth factors.” Also contributing to the Wisconsin study, which was supported bythe National Institutes of Health and the National ScienceFoundation, were Cheston Hsiao, Gisela Wilson, Kexian Zhu, LaurieHazeltine, Samira M. Azarin, Kunil K. Raval and Jianhua Zhang, allof UW-Madison.