Harvard Scientists report Progress in Stem Cell Production
Boston scientists have pioneered a fast and efficient new technique for turning adult cells into stem cells that is already changing laboratory practice and eliminates a major safety hurdle of eventually using such cells to treat patients.
- The discovery 4 years ago that ordinary skin cells can be transformed into powerful stem cells capable of developing into any type of cell in the body was a major breakthrough for scientists who have sought to harness the natural regenerative capacity of the body to heal patients;
- But the breakthrough came with a number of caveats: the method used to reprogram stem cells involved viruses and genes that modify the genome and could cause cancer.
The new technique, published online 9/30/10 in the journal, Cell Stem Cell, offers major improvements.
- The method does not involve dangerous genetic alterations, and is almost twice as fast as and up to 100 times more efficient than the standard method used to turn cells back to an embryonic-like state;
- The induced pluripotent stem cells, or iPS cells, that are formed more closely resemble embryonic stem cells than those made using standard methods;
“When we set about this project, we didn’t intend to tackle all these issues,” said Derrick Rossi, a stem cell biologist at Children’s Hospital Boston and the Harvard Stem Cell Institute who led the research. “Several of the major hurdles toward clinical translation of iPS cells are addressed by this technology, and that’s what we’re excited about.”
The Harvard Stem Cell Institute has already adopted the technique to make stem cells from patients, according to Douglas Melton, a stem cell biologist and co-director of the institute.
- Such cells allow scientists to study in a dish how a disease develops, while also holding the long-term promise of being used as treatments;
- Separately, the technology researchers developed might also offer a useful way to treat patients who suffer from genetic diseases in which their bodies lack crucial proteins, and a startup company called ModeRNA Therapeutics has been formed to explore that possibility.
In the stem cell technique first developed 4 years ago, scientists use a cocktail of viruses carrying genes to reprogram adult cells into stem cells. There have been various alternative approaches that have been developed since then, with limitations that made them impractical, Melton said.
- In the new work, scientists use messenger RNA, a molecule that carries instructions from the genome, allowing cells to translate the DNA blueprint into proteins;
- The scientists made a synthetic, modified messenger RNA and administered it to the cells daily, transforming them into stem cells;
- Daily dosing was necessary to maintain the correct amount of proteins needed to reprogram the cells;
- Since the RNA doesn’t modify the genome, cells can be reprogrammed without genetic modifications;
- They then used the same technique to cause the stem cells to turn into muscle cells, proving that the technology could also be used to help guide cells to develop into specialized types of tissue.
“This approach could have good potential of becoming a winner,” said Dr. Marius Wernig, an assistant professor of pathology at Stanford’s Institute for Stem Cell Biology and Regenerative Medicine who was not involved in the research. He said while it is impossible to tell which of the techniques now being worked on will ultimately succeed, this one has great promise. One area that will require further investigation is whether cells may be stressed since they need to receive RNA each day.
- Other scientists are continuing to work on alternate methods for making iPS cells;
- A team of scientists at McLean Hospital and a joint venture of Advanced Cell Technology, a stem cell company based in California and CHA Biotech of Korea, recently received a $1.9 M grant from the National Institutes of Health to pursue 1 such approach.
Scientists also said the new technique does not negate the need for human embryonic stem cell research. A federal court said Tuesday that such research could continue to be supported by federal funds while an injunction calling for a halt to the work is being appealed.
“Does this mean we’re done with human embryonic stem cells?
- I think all of us would like to find the day, as soon as possible” that we are done, Melton said. “Our goal is to make cells that are identical to embryonic stem cells. … [Rossi] wouldn’t even know if he were getting close to the goal unless he could use embryonic stem cells as the standard.” (HWM and C y Johnson, Boston Globe)