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Stem cells could boost supply of red blood cells
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Researchers have developed a method through which stem cells can be used to increase the production of red blood cells.
The discovery could significantly increase the blood supply needed for transfusions, according to the researchers.
“The ability of scientists to grow large quantities of red blood cells at an industrial scale could revolutionize the field of transfusion medicine,” Eric E. Bouhassira, PhD, a professor in the department of cell biology at Albert Einstein College of Medicine, said in a press release. “Collecting blood through a donation-based system is serving us well but it is expensive, vulnerable to disruption and insufficient to meet the needs of some people who need ongoing transfusions. This could be a viable long-term alternative.”
Blood transfusions are crucial to surgical procedures and blood cancer therapies. Donations currently are the only way to obtain blood. In addition to the expense and supply disruptions, the donation method also is inefficient for patients who require red blood cells expressing rare blood groups, according to background information in the study.
In vitro production of cultured red blood cells has emerged as a potential long-term alternative to donation-based methods. Several of the methods used to produce cultured red blood cells are based on the expansion of progenitors obtained from peripheral blood or cord blood.
“These methods could theoretically increase the blood supply because expansion of the progenitors from one unit of blood can yield multiple units of cultured red blood cells that could be used for production,” the researchers wrote.
To determine whether hematopoietic stem cell (HSC) expansion could be used to improve the yield of cultured red blood cells, the researchers compared cultured red blood cell yields with erythroid expansion (E-expansion) protocol.
Bouhassira and colleagues combined cell-expansion protocols into a “cocktail” that significantly increased the number of cells produced.
More than 10¹⁰ of cultured red blood cells can be generated using a single plate of embryonic stem cells. Combining HSC-expansion and E-expansion protocols significantly increased the yield of cultured red blood cells, according to researchers.
Researchers tested CD34+ cells derived from human embryonic stem cells, two 6- to 8-week yolk sacs, three 16- to 18-week fetal livers, three cord blood samples and two peripheral blood samples.
They found that the same in vitro conditions can be used to expand all of the cells.
Overall, fetal liver-derived cells had the highest proliferation potential. The three livers tested had a fold expansion of 3 x 10⁷, 2.5 x 10⁶ and 0.6 x 10⁶ in O2 conditions.
Using basic HSC-expansion for 1 week increased cell yield by approximately 10-fold, according to study results.
The combination of HSC and E-expansion in high-steroid conditions could lead to an additional one to two order-of-magnitude increases in the number of cells that can be produced from a single plate of human embryonic stem cells, the researchers said.
Large-scale production will require bioreactors to expand and differentiate the CD34+ cells into cultured red blood cells, Bouhassira and colleagues concluded.
“Being able to produce red blood cells from stem cells has the potential to overcome many difficulties of the current system, including sporadic shortages,” Anthony J. Atala, MD, director of the Wake Forest Institute for Regenerative Medicine and editor of the journal Stem Cells Translational Medicine, said in a press release. “This team has made a significant contribution to scientists’ quest to produce red blood cells in the lab.”
Perspective
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Jed Gorlin, MD
This is great science, and it is important to pursue the potential for “synthetic blood.” However, while it may be useful to be able to produce research quantities of very specific red blood cell antigen combinations to test various hypotheses, that is a long and distant way from being able to commercially produce red cells for transfusion to compete with a donated product. Simply put, just because you can do something doesn’t mean you ought to do something! It is significant that the first recombinant products were hormones, like growth factors or insulin, which require only microgram amounts to be active. This was followed by enzymes like coagulation factors, which work in milligram amounts. However, we transfuse red blood cells in gram amounts — specifically, there are more than 60 grams of hemoglobin in a standard red cell unit. Simply adding up the cost of all the cell culture reagents required to synthesize this amount of protein would greatly exceed the current real cost of about $200 per red cell. Therefore, this makes great science but a very dubious business plan. Caveat emptor!
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