US scientists have developed an efficient way to make mature red blood cells on a large scale using human embryonic stem cells to make young red blood cells and then maturing them in the lab. The development opens the possibility of making almost unlimited amounts of transfusion blood in the lab although experts caution there are still many hurdles to overcome.

The research was the work of scientists at Advanced Cell Technology in Worcester, Massachusetts, the University of Illinois at Chicago and the Mayo Clinic in Rochester, Minnesota and was prepublished online as a First Edition Paper in the journal Blood on 19 August 2008.

Human erythropoiesis, the process by which red blood cells (erythrocytes) are made in the human body, is complicated. In an adult, red blood cells are made in bone marrow, but in an an early embryo they are made in the mesodermal cells of the yolk sac, then the process moves to the spleen and liver and later to the bone marrow. There are also several differentiation stages from stem cell to red blood cell.

In this paper the researchers said they were able to differentiate and mature human embryonic stem cells into functional oxygen-carrying red blood cells on a large scale.

Red blood cells are important because they carry life-essential oxygen to every cell of the body. One way to assess whether red blood cells are fully functional is to measure their oxygen-carrying capacity and stability, by monitoring what hematologists call oxygen equilibrium curves.

The researchers said they demonstrated that the oxygen equilibrium curves of the red blood cells they derived from human embryonic stem cells were comparable to normal red blood cells and responded to changes in pH and 2,3-diphosphoglycerate, key tests of ability to carry and release oxygen.

Although the stem-cell originated red blood cells were more like fetal and embryonic blood cells than adult cells, they did show some adult cell characteristics after maturing in vitro. The maturing process increased the beta-globin count from 0 to over 16 per cent. Beta-globin is the most common type of the blood protein hemoglobin in adult blood.

The scientists said that most important of all, was that the cells went through several stages of maturation, including progressively getting smaller, and gradually displaying more adult cell characteristics such as expression of other important proteins and nuclear condensation, with over 60 per cent of the cells showing the right kind of ageing process in the nucleus.

The researchers concluded that:

“The results show that it is feasible to differentiate and mature [human embryonic stem cells] into functional oxygen-carrying erythrocytes [red blood cells] on a large scale.”

The researchers hope this will one day lead to a universal donor supply of O-type negative red cells for transfusion, reported the Associated Press.

Deputy director of the National Heart, Lung and Blood Institute in the US, Susan Shurin, described the results as an “important first step”. She told Scientific American that:

“They’ve grown these in the test tubes and been able to get them to mature so that many aspects of these cells look like [red blood cells] that you make and I make.”

“But they haven’t given them to people and see if they survive,” added Shurin.

One big problem will be the immune system, which will pick up things like the wrong kind of sugars on the surface of the red blood cells. If they don’t match what it is expecting, it will treat the red blood cells as unwanted foreign agents and kill them. There’s a lot of work to do, said Shuring, but “it’s a significant step in the right direction”.

“Biological properties and enucleation of red blood cells from human embryonic stem cells.”
Shi-Jiang Lu, Qiang Feng, Jennifer S. Park, Loyda Vida, Bao-Shiang Lee, Michael Strausbauch, Peter J. Wettstein, George R. Honig, and Robert Lanza.
Blood First Edition Paper, prepublished online August 19, 2008.
DOI 10.1182/blood-2008-05-157198.

Click here for Abstract.

Source: Journal abstract, AP, wikipedia, Scientific American.

Written by: Catharine Paddock, PhD