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November 17, 2010

Can stem cells end the need for blood donors?

by Paul Krzyzanowski

In a previous post, Chris Kamel recently reviewed the Nature article about direct creation of blood progenitors from skin fibroblasts as discovered by Mick Bhatia's research group. The fascinating thing about this article is the potential for enabling autologous cell treatments with a reduced risk of iPS-cell-induced cancer.

Certainly, no one can deny that creating a clinically usable substitute for matched bone marrow from a person's own skin cells would be a phenomenal accomplishment. In my view, what this advance can really accelerate is work to produce methods of culturing human hematopoietic stem cells with the goal of producing artificial whole blood. Bioreactors are routinely used to expand hematopoietic stem cells and producing whole blood is only a (large) step away.

The demand for blood and blood substitutes is large and growing. According to the American Red Cross, approximately 15 million litres of blood were used in transfusions in 2006, and that's only taking the United States into account. This amount is expected to grow in the future, and with the individual components of whole blood having short shelf lives -- six weeks for red blood cells and only one week for platelets -- a constant supply of blood from donors is needed.  

Dr. Dana Devine, Vice-President of Medical, Scientific and Research Affairs at Canadian Blood Services said that cultured blood products might someday help part of this need. "There is a lot of transfusion research science currently ongoing worldwide " she said, noting that the use of skin derived stem cells to replace autologous blood cell collection might be possible for patients with adequate time to wait for cell culture (for example those undergoing elective surgery or chemotherapy), however “the tissue engineering and scale-up issues in turning these kinds of research scale studies into a cost-effective product remain a challenge.”  

The volume of blood required for some procedures is surprising: a liver transplant procedure might use up to one hundred units (45 litres) of blood, according to the Canadian Blood Services website. As less than 40% of the population is eligible to donate blood, those in need of rarer blood types may be out of luck if an appropriate donor hasn't recently come forward within the same geographical location.  

As well known medical procedures, blood transfusions serve two major purposes. One is to replenish volume from blood loss after trauma or during surgery, while the other is to restore the oxygen carrying capacity of the circulatory system. Most volume-expanding blood substitutes are more or less salt solutions, which don't restore the oxygen carrying capacity provided by red blood cells. The products that actually do restore this capacity are divided between perfluorocarbons and various hemoglobin solutions, the latter usually derived from bovine blood.

However, development of bovine hemoglobin products hasn't been easy. None are approved for general use, and those undergoing clinical trials today are in no way guaranteed to gain approval. Up until recently, Biopure was a company producing Oxyglobin, a viable oxygen-carrying product approved for veterinary use, but primarily pursuing approval for a similar product for use in humans called Hemopure. Failing to get approval, the company began to run out of funds in early 2009 and filed for bankruptcy soon thereafter. Some may also recall the Canadian company Hemosol (Now Hemosol BioPharma) formed in the 1980's to commericialize Hemolink, a human hemoglobin based oxygen carrier. Like Biopure, Hemosol filed for bankruptcy in 2005, and both were examples of firms developing their products over the span of two decades or more. Many other blood substitutes like these have been pulled from trials due to safety concerns, including vasoconstriction and pain accompanying their transfusion. 

Producing blood from stem cells may finally be the technology that becomes successful in this space, as erythrocytes (red blood cells) can be produced from human iPS cells. These laboratory studies are establishing principles to show that red blood cells can be generated on a larger scale, and raise the possibility that, in the future, problems of limited blood supplies being available may be reduced or nearly eliminated.  "Though we currently don't have ongoing shortages of blood products in first world blood systems" said Dr. Devine, "there are significant shortages in the developing world."

"However, for the foreseeable future, we still need blood donors to make the system work."

 

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