After two decades of research, scientists are on the cusp of entering a new era in stem-cell research that may transform the landscape of genetics and disease therapy.
In a first-ever clinical trial, researchers from Harvard University have created “blood-forming stem cells,” which they hope can one day serve to ameliorate genetic blood disorders and other conditions.
“We’re tantalizingly close to generating bona fide human blood stem cells in a dish,” said senior investigator George Q. Daley, Dean of Harvard Medical School and head of a research lab in the Stem Cell Program at Boston Children’s Hospital. “This work is the culmination of over 20 years of striving.”
While scientists first isolated embryonic stem cells in 1998, they have found little success in the years since in using them to create legitimate blood-forming stem cells.
However, Daley tapped into years of work that had been done previously, including his team’s creation of the first induced pluripotent stem (iPS) cells in 2007. While the team previously was able to use the iPS cells to produce other kinds of human cells, including brain and heart cells, they had no luck in their pursuit of blood-forming cells.
That is, until now. And the breakthrough puts them on pace to make a tremendous impact on patients with genetic disease, according to the study authors.
“This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells,” said study author Ryohichi Sugimura, a postdoctoral fellow in the Daley lab.
Overcoming Key Challenges
Currently, the approach of the Harvard researchers includes using viruses to alter the genetic material within the blood-forming cells that they have created. But their “ultimate goal is to expand their ability to make true blood stem cells in a way that’s practice[sp] and safe, without the need for viruses” to signal genetic change.
Their new research may have cleared one long-standing barrier in the way of that realization.
“It’s proved challenging to ‘see’ these cells,” said Sugimura. “You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can’t go back and study it – it’s already gone.”
“A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona fide human blood stem cells,” added Sugimura.
To test the potency of their new approach, the Harvard team transplanted blood-forming cells into mice. After several weeks, some of the mice “carried multiple types of human blood cells in their bone marrow and circulating blood,” which means that the cells were actively working to create new blood cells within the animals’ bodies.
“We’re now able to model human blood function in so-called ‘humanized mice,’” said Daley. “This is a major step forward for our ability to investigate genetic blood disease.”
The study appears online in the journal Nature.