Does the Future Rest on Stem Cells?

In an article that appeared in the January 2005 edition of Nature Biotechnology, Dr. Narla Mohandas, the Vice President for Research and Lab Head at the New York Blood Center, wrote a review article indicating the use of stem cells as a means of producing an alternate source of transfusable blood. Dr. Mohandas first introduces the long term dream of scientists to produce red blood cells ex-vivo, in the lab. After all, there is indeed no better substitute for blood than red blood cells themselves. Dr. Mohandas then points to a study done by Giarratana et. al., which might be the first significant steps towards making this dream a reality.

In their study, Giarratana describe a large-scale ex-vivo production of mature human blood cells using hematopoietic stem cells of diverse origins through a complex culture process. Moreover, Dr. Mohandas highlights the fact that these blood cells produced in culture possess the same hemoglobin content and morphology as do native red blood cells. In addition, the authors of the study contend that the red blood cells they produced have a near-normal lifespan, when compared to native red blood cells – an important characteristic that hemoglobin-based blood substitutes fail miserably short on.

The major obstacle with this method of producing red blood cells, according to Dr. Mohandas, is cost. At the moment, the complex three step method of producing the cells would make a unit of these red blood cells too expensive. However, Dr. Mohandas stresses the significance of this protocol as the first of its kind that has made the production of red blood cells which closely resemble native red blood cells possible on a large scale. It is a discovery that signifies how far the scientific community has come in its search for an alternate source of transfusable blood, and it gives tremendous hope for the future. Indeed as technology progresses, this method of producing red blood cells may very well come to fruition as a commercial product – and sooner than we think.

Interview with Dr. Narla

1. Your review article entitled "Banking on red blood cells" in Nature Biotechnology is over a year old now. Has any significant progress been made with the production of red blood cells from stem cells?

To my knowledge there have not been any follow-up papers on this subject. I was hoping that publications from other laboratories would have reported replication of these interesting findings. My own view is that significant advances in our ability to manipulate embryonic stem cells and in biotechnology are needed to make this interesting laboratory exercise into a practical product. My own view is that this is not likely to happen in the next decade due to technical hurdles that need to be overcome and prohibitive cost of such a product.

2.Are you familiar with some of the new developments being made with hemoglobin based oxygen transporters (namely, Dr. Robert Winslow and Sanagart’s work with Hemospan and Dr. Steven Kaganov's work with dendrimeres at Dendritech)? If so, do think any of these products could be successful? Or, in your mind, has the window of oppurtunity for hemoglobin based oxygen transporters passed unto the use of stem cells?

There are on going clinical trials by Sangart with hemoglobin based oxygen transporters. My view is that this product which appears to have solved some of the earlier problems with other formulations continues to prove to be safe and efficacious, and will likely make a significant contribution in severe trauma situations. My only hesitation for not being more enthusiastic is that many previous formulations encountered problems during Phase III trials. We should know more about this product in the next year or two. I am not familiar with the Dendritech product.

In terms of window of opportunity, because of our detailed understanding of hemoglobin structure and function, I think hemoglobin based oxygen transporters are still very much in play. Stem cell based blood products are in very early stages of development and a lot of research and development needs to take place before they can become viable products.

3.Our research shows that a unit of blood costs a hospital around $500, when you take into account the regulatory procedures and tests which all donated blood is subjected to. Can you estimate how expensive a unit of red blood cells produced by stem cells would be? How expensive a unit of hemoglobin based oxygen transporters would be currently?

My own estimate is that production of a unit of red cells from stem cells at this stage will be prohibitively expensive because of the complex three stage culture system that needs to be deployed. While it is difficult to project the cost of manufacture, a reasonable guess on my part will be $5000 to 10,000 at a minimum. I do not know the current cost of hemoglobin based oxygen transporters but the process of making them is much less complex. However, the price charged in health care has no real bearing to cost of manufacture in my view.

4.) What would you say to the scientific community who would like to put the search for blood substitutes on the "back burner" and allocate research and resources elsewhere? How important is it that we find a substitute that could be used commercially?

I still think there is a great need for an effective blood substitute in trauma centers. A rationally thought out investment in developing effective products is still worth while.

5. Finally, where do you see this field going in the next 5-25 years?

I think there will be continued development of hemoglobin based oxygen transporters during the coming decade. In terms of stem cells I think a great deal of basic science developments and improvements in cell processing technology have to be made to derive a viable commercial product. I do not foresee such a product in the next decade.