Researchers at the RIKEN BioResource Center in Tsukuba have established several cell lines that produce functional red blood cells (RBCs) from mouse embryonic stem cells. The technique may pave the way for production of human donor RBCs in vitro, lessening the need for blood donation.
The research team led by Yukio Nakamura initially induced hematopoiesis—that is, differentiation from the stem cell into more mature blood and immune system cells—in mouse embryonic stem cells by culturing the stem cells on a layer of so-called feeder cells in the presence of specific growth factors as well as the synthetic steroid drug dexamethasone.
The team reports they established a total of five cell lines by this method. Three cell lines exhibited characteristics of erythroid, or RBCs. The other two lines exhibited the characteristics of mast cells, a type of immune system cell.
Analysis of the three erythroid cell lines demonstrated that the cells expressed genes specific for erythroid cells. Furthermore, the cells expressed α and β globin chains, which are only expressed by adult erythroid cells. By altering the growth conditions, the team could induce cells to further differentiate in vitro into more mature erythroid cells, including RBCs.
Next, the researchers examined the ability of the erythroid cell lines to produce RBCs in vivo in mice suffering from acute anemia. The injection of the erythroid cell lines ameliorated the anemia, suggesting that differentiation of the injected cells occurred in vivo to produce RBCs similar to those produced naturally by the host mouse.
The researchers also evaluated the potential for the cell lines to form tumors in vivo as some stem cell lines have been associated with tumorigenicity. Mature RBCs lack a nucleus, and hence lack DNA, so carry little risk of tumorigenesis, but the less mature cells produced by the cell line do contain DNA. After transplanting the cell lines into mice, no tumors were observed for 6 months, suggesting that these cell lines were not tumorigenic.
Nakamura says it should be possible to use the same method to produce human erythroid cell lines capable of producing RBCs, platelets, and other useful blood cells, which could reduce dependence on volunteer blood donations.
“There is little doubt that RBCs, platelets, and neutrophils produced in vitro would be candidate materials to replace cells donated from such a large group of anonymous individuals,” he notes.
Illustration: Microsoft clipart.
RIKEN BioResource Center News Release (05/23/08)
The Post Chronicle (05/24/08)
Abstract (Public Library of Science ONE; 3(2) (02/06/08))