Scientists have found a way to reliably grow large quantities of heart cells from human embryonic stem cells - a feat that marks a significant step toward generating replacement tissue for failing hearts.
Using a recipe of growth-factor proteins that mimics heart development in a fetus, researchers from Canada, the U.S. and England were able to transform embryonic stem cells into a crucial cardiovascular progenitor cell - the most immature heart cell identified to date.
In turn, the progenitor cells generated 20 to 30 million mature heart cells per experiment, yielding three of the major tissue types necessary for a healthy heart - endothelial cells, vascular smooth muscle cells that line blood vessels, and cardiomycocytes, the heart's hallmark cells that contract and beat in unison.
"With this approach ... we now have a renewable source of human heart cells," said Gordon Keller, director of the McEwen Centre for Regenerative Medicine in Toronto and senior author of the report published Wednesday in an online edition of the journal Nature. "The hope is that we can do some remarkable things with [them]"
The most immediate application is that researchers can use the cells to study how heart cells develop and function and how they will respond to drugs. Further down the road, the progenitor cells could be cryo-preserved and used as needed to patch scarred hearts, or perhaps grown into tissue implants.
"In the future, these cells may also be very effective in developing new strategies for repairing damaged hearts, following a heart attack," Dr. Keller said.
Researchers did transplant the progenitor cells into the hearts of specially bred mice and found the implanted cells grew into the different cell types and seemed to improve the function of the rodents' hearts.
Other researchers have coaxed heart cells to grow from human embryonic stem cells, which have the ability to grow infinitely and become any tissue type in the body. But numbers have not been highlighted in previous efforts, in which the cultures might also be contaminated by other cell types.
The concern, Dr. Keller explained, is that any implant that contains a "lingering stem cell ... could form a teratoma tumour in transplant." Teratoma tumours are growths that contain various tissue types, such as hair, teeth and bone.
While Dr. Keller stopped short of saying their cultures are "purified" heart cells, he said researchers could not detect any contaminating cells in their cultures and that they appear to be "highly, highly enriched" with cardiac cells alone.
"By capturing this progenitor we have ensured that we can pretty much get the same product at the end of the day."
Mick Bhatia, scientific director of the McMaster Stem Cell and Cancer Research Institute in Hamilton, said the report is significant because it describes for the first time the exact route, "the stop signs and signals" an embryonic stem cell takes to become a cardiac cell and the steps needed to direct it.
"It's helpful as we start thinking about using these cells toward therapies," Dr. Bhatia said. "We still don't know if that's going to give us what we want - which is to regenerate a heart in a human - but it is a step in the right direction."
The research team identified the progenitor cell by a protein marker, known as KDR, on the surface of the cells after they had been exposed to a sequence of particular growth factors, or proteins. Once the progenitors were identified, Dr. Keller said it took about five or six days for them to grow into the three types of mature heart cells in a special culture.
While the method produces high numbers of heart cells, he said it would still have to be "scaled up" from a Petri dish to generate enough heart cells for a tissue graft implant of some kind, he said.
The team relied on human embryonic stem cell lines from Singapore and the U.S. to do the work. Research on human embryonic stem cells remains controversial because, generally, embryos must be destroyed to harvest the cells.
But Dr. Keller noted that the cell lines used in the experiment were approved by both Canada's Stem Cell Oversight Committee and the U.S. National Institutes of Health.
However, Dr. Keller said efforts are now under way to reproduce their results with "reprogrammed" stem cells. Scientists from the U.S. and Japan announced last fall that they had managed to "reprogram" ordinary human cells to behave like embryonic stem cells with the addition of four genes.
Research into the potential and safety of the reprogrammed cells is ongoing. But they are considered ethically acceptable in contrast to stem cells from human embryos, and more valuable for medical treatments. This is because a cell could be taken from a patient, reprogrammed and, theoretically, used to produce a stem cell therapy or tissue transplant that would perfectly match the cells of the patient in need.
"The important test will be whether the reprogrammed cells will behave the same way [in producing the heart progenitor cells]" Dr. Keller said.