Stem cell pioneer's major multinational discovery may speed research

There's a new class of stem cell that's exciting researchers around the world – and it was discovered by an international  team of almost 50 scientists on four continents, led by U of T researchers.

Headed by Professor Andras Nagy of obstetrics and gynaecology and the Institute of Medical Sciences, the team conducted the first high-resolution characterization of molecular events required for the formation of stem cells from specialized cells – a process called cellular reprogramming. And it identified a new type of stem cell, called F-class. 

It's an advance that opens fresh avenues for generating designer cells that could be safer and more efficiently used in therapy. 

The discoveries, dubbed Project Grandiose for the massive scale of the scientists' undertaking, were heralded by the simultaneous publication of five scientific articles in the journals Nature and Nature Communications and grabbed headlines around the world. (See the CBC coverage; read the Toronto Star article; read the TIME magazine article; read The Australian's coverage.)

“It was an enormously enlightening feeling that a single scientific question was able to transcend geographical distances, time zones, international borders and cultural differences,” said Professor Nagy, also of Mount Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute. “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.”

Stem cells hold enormous promise for the treatment of currently incurable diseases. The molecular changes that lead to stem cells during reprogramming are starting to be uncovered. The detailed analyses of the data generated and now reported in the five papers will help to better understand this process which is critical to generating safe and highly-efficient sources for therapeutic cell production. 

“We are incredibly proud of Dr. Nagy's leadership of this extraordinary team,” said Professor Jim Woodgett, Lunenfeld's director and a professor in U of T's department of medical biophysics. “Every one of the researchers involved in this historic effort is driven by their desire to improve therapies for patients. These papers reinforce how strategic investment in the best scientific research can truly transform our understanding and lead to new therapeutic possibilities.” 

The extremely in-depth analysis of the process of reprogramming specialized cells to stem cells focused on learning how to control the path to either the new F-class stem cell versus “traditional”, embryonic-like stem cells. Comparing the two cell types revealed that the new class of stem cells is easier, less expensive and faster to grow compared with the embryonic-like stem cells. Because of these properties, the new F-class stem cells can be produced more economically in very large quantities, which will speed up drug-screening efforts, disease modeling and eventually the development of treatments for different illnesses.
 
The Nagy Laboratory at the Lunenfeld is historically a stem cell laboratory. It was the first to report a method of producing stem cells without the need for viruses that could harm the genetic material. This work was published in 2009, also in the journal Nature. For this discovery Dr. Nagy was selected for the first annual Scientific American Top 10 Honor Roll in 2009, a list that included such leaders as  U.S. President Barack Obama, Bill Gates and Michael Bloomberg.

In 2010, Professor Nagy received financial support from the Ministry of Science and Innovation of Ontario, his industry partner Pfizer, the Canadian Institutes of Health Research and the McEwen Centre for Regenerative Medicine to carry out the research that resulted in the current five publications.This support allowed his group to engage with other stem cell research experts from laboratories in Australia, South Korea and The Netherlands. The resulting consortium generated and analyzed an unprecedented dataset, uncovering the molecular events underlying biological processes of cell fate change toward stem cells.