Combating Blood Shortage: In vitro Red Blood Cells

Combating Blood Shortage: In vitro Red Blood Cells

By Sharon Washio

At any given time, or more exactly every 2 seconds, blood transfusions are needed for complicated surgeries, treatments, accident victims, sickle patients, pregnancy complications, severely anemic children, and more. While blood can be donated even concurrently with the use of medications like aspirin, and in the U.S. approximately 38% of the population is able to donate, less than 10% do, according to the Red Cross. Even donated blood does not last forever and there is a constant shortage problem that, unless donors increase, is projected to rise due to longer lifespans, the limited shelf life of blood, blood requirements, and the specificity of blood types. The scarcity of blood supplies often prevents necessary surgeries and treatments from reaching a loved one.

The appeals of in vitro blood, or blood made in a laboratory setting, is that it is more reliable and safe than in vivo blood, which must undergo screenings prior to use. Recently, researchers K. Trakarnsanga, R. Griffiths, M. Wilson et al. developed the Bristol Erythroid Line Adult (BEL-A), the first human immortalized blood line that successfully undergoes erythrocyte reproduction. Prior to this, efforts to cultivate blood in vitro through means such as pluripotent stem cells, adult peripheral blood, and umbilical cord blood had encountered the problem of producing cells with nuclei, which is problematic because normally red blood cells do not contain nuclei as that would diminish their functionality.

In this study, cells were immortalized by the integration of the Human Papilloma Virus (HPV) gene. This was done by using a Tet-inducible HPV16-E6/E7 expression system on adult bone marrow, which is the location of blood cell production. Immortalized cells are mutated in a way that they engage in constant cell cycles, though they do not overpopulate in the way that cancer cells do. Throughout the experiment, the researchers froze the cells periodically and the cells were shown to maintain function after thawing. Over 100 days, the cells were very stable, exhibiting no change in shape or quality. Centrifuging the samples demonstrated their ability to carry oxygen through the production of red pellets, which indicated the presence of the protein hemoglobin. The cultures were then exposed to the antibiotic doxycycline for six days to enucleate them and make them mature, with a 30% of the samples effectively losing their nucleus and the rest filtered out for future use. The successful mature cells also lost the HPV gene after being treated with doxycycline.

The researchers compared their samples to cells made from adult peripheral blood, and found the size and the shape of the immature and mature cells of the two samples to be similar, even during replication. The blood type of the sample corresponded to that of the donor whose bone marrow they used. As for the immature red blood cells or reticulocytes, they are often used in tests of bone marrow conditions. The reticulocytes produced in this experiment were found to have the same types of proteins as normally produced reticulocytes in adults. When reintroduced into the human body, the reticulocytes matured as expected and carried out red blood cell functions.

Yet, even though this is undoubtedly a huge turning point in medicine in progress, the regular use of artificial blood in clinical settings is still a far reality and an increase in blood donations is still essential.

Even in a continuously stirred system, the growth of the BEL-A line remained stagnant, which is a factor to be considered for large-scale production. Future investigations include successfully enucleating more of the samples and working on more efficient ways of separating the blood into mature and immature cells. Apart from that however, not only is BEL-A a viable adult cell line, but it also allows for meticulous testing to be done on related diseases such as anemia, leukemia, sickle cell disease, parasites and more. It is exciting to think of the possibility of needing only a few donors of every blood type to sustain the different lines, and of the prospects of being able to donate blood to developing countries that do not have access to a safe supply. Yet, even though this is undoubtedly a huge turning point in medicine in progress, the regular use of artificial blood in clinical settings is still a far reality and an increase in blood donations is still essential.


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