stem cells to form endothelium
(green), then blood cells (red)
Credit: Irina Elcheva
and Akhilesh Kumar
Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.
The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.
This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.
“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.
He and his colleagues described this method in Nature Communications.
During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.
Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.
These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.
“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.
Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.
The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.
This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.
“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.
He added that his group is still working on a method for producing hematopoietic stem cells in the lab.
“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”
