Scientists skip embryonic stem cells to turn skin into beating heart cells
Researchers have found a way reprogram skin cells directly into beating heart cells.
The scientists say the technology used to change skin cells directly into heart cells could help treat a wide range of conditions that occur from tissue loss including Alzheimer's, heart disease and Parkinson's disease, bypassing technical and safety issues associated with reprogramming embryonic stem cells.
Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study says, "We hope it helps overcome major safety and other technical hurdles currently associated with some types of stem cell therapies." The work is a major shift in reprogramming stem cells because it bypasses the need to use embryonic stem cells and instead uses mature cells that can be turned directly into brain, heart or pancreatic cells.
Because there are multiple hurdles working with embryonic stem cells, the researchers have been trying to find ways to bypass the process.
They explain that as cells mature from an embryonic state into adult cells, their ability to generate new cells is lost. The goal of scientists has been to reprogram adult cells back into a pluripotent, or embryonic state and turn them into the types of cells needed to repair damaged tissue.
A 2006 Japanese study showed researchers were able to reprogram mouse skin cells by inserting four genes,
“It takes a long time to generate iPS cells and then differentiate them into tissue-specific functional cell types," said Ding, "and it’s a tedious process. Also, what you generate is not ideal.” He explains it takes weeks to transform induced pluripotent stem (iPS) cells into other types of cells - when it happens only one cell out of thousands might make the transformation.
When the researchers use iPS cells, many of the original type cells linger. The scientists fear injecting iPS cells back into a patient could cause cancer, something that happens in mice.
The scientists turned skin cells directly into beating heart cells by switching off gene activity after a few days in skin fibroblast cells, rather than allowing them to remain continuously active. After the genes were switched off the scientists gave the cells a signal that turned them into heart cells.
“In 11 days, we went from skin cells to beating heart cells in a dish,” said Ding. “It was phenomenal to see.” The researchers now have a better understanding of how to generate new cells, bypassing the need, technology hurdles and time it takes to use embryonic cells to regenerate tissue.
He adds, “It is like launching a rocket," he said. "Until now, people thought you needed to first land the rocket on the moon and then from there you could go to other planets. But here we show that just after the launch you can redirect the rocket to another planet without having to first go to the moon. This is a totally new paradigm.”
They hope to be able to avoid injecting the four genes needed to reprogram cells that could generate tumors and shown in mouse studies.
Scientists could then turn adult cells directly into whatever type of cells are needed to repair damaged tissue, without safety and technical hurdles. In the current study, the scientists took skin cells and turned them directly into beating heart cells in 11 days, an accomplishment they say, "presents a new paradigm in stem cell reprogramming."
Nature Cell Biology: doi:10.1038/ncb2164
"Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy"
Jem A. Efe,Simon Hilcove,Janghwan Kim,Hongyan Zhou &Sheng Ding