A Toronto-led team has mapped the process of making a stem cell for the first time, opening new opportunities for future stem-cell research.
In the process, they discovered that a kind of stem cell they had previously believed was useless is, in fact, easier to grow than some others and could transform future therapies in regenerative medicine and the search for new drugs.
Andras Nagy of the Lunenfeld-Tanenbaum Research Institute at Toronto's Mount Sinai Hospital headed the study, which looked in unprecedented molecular detail at how a stem cell develops. The result is a detailed account of all 17,000 genes in the cell studied, and the molecules they produce during the three weeks it takes for a stem cell to develop in a laboratory dish. The data, published on Wednesday in the journal Nature, are publicly available on the web-based portal Stemformatics.
"The data sets emanating from the project will be a gold mine for the stem-cell field, and are likely to yield new and exciting revelations on many molecular aspects of the 'reprogramming' process," said Nadia Rosenthal of the Australian Regenerative Medicine Institute, who was not involved in the study.
"Reprogramming" is a process by which adult cells, such as those found in the skin, are turned into stem cells. It was discovered eight years ago by Kyoto University's Shinya Yamanaka, who won the Nobel prize for it in 2012. In 2009, Dr. Nagy improved the technology by eliminating the need to use viruses that could harm the cell's genetic material.
Using the new technology, Dr. Nagy's lab grew billions of cells for the current study, which were then collected, at precise time intervals, as snapshots of a cell's trajectory towards becoming a stem cell. An international team of scientists did the molecular analysis of the snapshots. Scientists in South Korea measured the activity in each of the 17,000 genes; gene products, such as RNA and proteins, were measured in Australia and the Netherlands, respectively.
Because of the scope and detail of the study, those involved called it "project grandiose."
"It was an enormously enlightening feeling that a single scientific question was able to transcend geographical distances, time zones, international borders and cultural differences. Each of the close to 50 scientists with unique expertise contributed to a unified product which none of us as individuals could even get close to," Dr. Nagy said.
Stem cells hold great therapeutic potential because they are pluripotent, meaning that they can turn into any cell type in the body. Scientists believe degenerative diseases, such as kidney disease and Parkinson's, might be cured by replacing the damaged cells with new ones grown from stem cells.
Sourcing these cells directly from the patients prevents rejection of the resulting transplant tissue.
One surprising finding was that cells, previously dismissed as "junk" because they did not look like the other stem cells are in fact a new kind.
"Everybody thought it was just rubbish. They discarded those cells," says Dr. Nagy.
These new stem cells, called F-class for their "fuzzy" appearance, might be better suited than others for industrial and clinical application because they grow faster and thrive in cheaper media.
One safety issue with stem cell therapy is the fact that stem cells rapidly divide and could cause cancer after being transplanted and it has been challenging to derive transplant tissue free of any remaining stem cells.
"Fuzzy" stem cells can be readily transformed into cells like neurons, leaving no stem cells behind in the dish. This raises the possibility of a safer, cancer-free therapeutic application.
Ian Rogers of Mount Sinai hospital, one of the authors of the study, is using the data to make kidney cells more efficiently to repair kidney damage.
"We would be very happy if others are going to start to analyze and mine this data. This is probably just the tip of the iceberg. And we would like to continue the mining of the 90 per cent of it that is below the water but we hope others will also do it," Dr. Nagy said.
Dr. Nagy initiated the project in 2010 with a $4.5-million grant from the Ontario ministry for research and innovation.