Scientists bring 'limitless blood supply' closer to reality

For the first time, scientists have generated blood-forming stem cells in the lab, an advance that brings them "tantalisingly close" to create a limitless supply of human blood to treat blood diseases.
Researchers, who used pluripotent stem cells that can make virtually every cell type in the body, said that the study may help create immune-matched blood cells, derived from patients' cells, for treatment purposes.
"We're tantalisingly close to generating bona fide human blood stem cells in a dish," said George Daley, from the Boston Children's Hospital in the US.
Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they are capable of generating multiple types of human blood cells when put into mice, researchers said.

"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 Ryohichi Sugimura, a postdoctoral fellow at the Daley Lab.
"This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions," Sugimura said.

Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells.

"This work is the culmination of over 20 years of striving," said Daley, who is also the dean of Harvard Medical School in the US.
In 2007, researchers generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming.
These cells were later used to generate multiple human cell types, such as neurons and heart cells - yet blood- forming stem cells remained elusive.
Researchers combined two previous approaches to successfully generate hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells.
They then added genetic regulatory factors to push the tissue toward a blood-forming state.

Researchers identified five candidates (RUNX1, ERG, LCOR, HOXA5, and HOXA9) that were both necessary and sufficient for creating blood stem cells.
They transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation.
These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets, and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination.
"We're now able to model human blood function in so- called humanised mice. This is a major step forward for our ability to investigate genetic blood disease," said Daley.