Oct. 15, 2013
In vitro production of red blood cells from iPS cells
RIKEN No.: 08054
Inventors
Yukio Nakamura and Ryo Kurita (RIKEN BRC Cell Bank)
Background
In vitro production of red blood cells (RBCs) offers a potential means to overcome a shortage of transfusable RBCs and also to provide a source of cells free from possible infection or contamination by microorganisms.
Summary
We have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs.
Since the established cell line produces hemoglobin constantly and abundantly, the cell pellet is red. Photos in figure 2 indicate immunostaining (left) and bezidine stainings (right) of the enucleated RBCs. In the immunostaining the arrow indicates enucleated RBC which is stained with anti-Glycophorin A antibody (pink) but does not possess nucleus (green). Also, in the bezidine stainings, the arrows indicate enucleated RBC which is stained with benzidine (brown, left photo) but does not possess a nucleus (light blue, right photo). The established cell line can produce hemoglobin with oxygen binding and dissociation abilities equivalent to RBCs produced in vivo.

Fig.1: Cell pellet of immortalized cell line (left), and
oxygen-carrying capacity of the immortalized cell line (right)

Fig.2: Immunostaining (left) and Bezidine stainings (right) of the enucleated RBCs
Merits
Immortalized human erythroid progenitor cell lines can proliferate vigorously and eternally. Furthermore, they can produce enucleated RBCs in a few days. Of note, enucleated cells will never form any tumor after transfusion.
Applications
If we could establish an immortalized cell line able to produce O/RhD(-) RBCs, the RBCs produced from such cell line could be transfused to the vast majority of people around the world.
References
- 1.Japanese Patent No.62886152, US patent 8975072
- 2.Kurita, R., Suda, N., Sudo, K., Miharada, K., Hiroyama, T., Miyoshi, H., Tani, K., and Nakamura, Y. PLoS ONE 8: e59890 (2013)