I had an idea come to me during Biology class and I immediately asked my teacher, but she couldn't really answer the question, so I'll ask it here.

What are the limiting factors in the production of synthetic red blood cells with no antigens? I mean, we do have the human genome mapped, but am I naive to think that we have genetic technology capable of doing this?

If red blood cells are too complex to manufacture, is it feasible to manufacture much smaller particles of just hemoglobin inside small spheres of cell membrane and use that as a temporary replacement for red blood cells?

(I was at a medical research talk a while ago and one professor was explaining that there are many other proteins bound onto a red blood cell that aren't of the ABO or RH system. Normally this isn't a problem for recipients who only occasionally received transfusions but for people who need a long-term supply of blood, their bodies do get sensitized to the foreign proteins and will eventually start attacking the foreign red blood cells).


Actually there are such particles. It is estimated that about 20% of the hemoglobin (HGB hereafter) is in HGB vesicles (HbV hereafter) formed by RBCs. So sure, it is possible to use small particles instead of RBCs, but these vesicles have major and minor antigens on their surface. According to some of the articles they cause other complications too by blood transfusions and they are destroyed by the immune system within 3 to 7 days. So they don't solve the problem.

HGB vesicles without major and minor antigens are not a perfect solution either (I think), because the immune system tends to attack such things. For example by viral infections the MHC1 levels are low (in cells with nucleus) to avoid T cell response and the NK cells does not like that, so they destroy such cells. I am almost sure something similar would happen with this kind of vesicles as well. At least afaik. the immune system checks not just the presence of these antigens, but their composition as well. So if a RBC is under stress, then it changes the antigen composition on its surface and the leukocytes destroy it if necessary. According to some of the experiments PEG can cover HbV antigens and increase immune compatibility, so having less surface antigens seems to be a better choice than having more.

HGB vesicles have another problem. The HGB inactivates in them without reduction (metHb formation). Only Fe2+ HGB can carry oxygen. This can be solved with methylene blue according to this study.

We cannot use free HGB either, because it would decrease the NO levels and lead to endothelial dysfunction. I think to small particles would have the same effect because of increased surface.

According to other studies RHSA-heme (serum albumin bound to synthetic heme) is another option. It seems to be safe if you replace only 20% of blood volume (of rats). I think a complete transfusion is not safe, because it would reduce the NO levels as we already discussed. I have not found an experiment which does complete transfusion.

So there is ongoing research in the topic. There is progress, but none of the current solutions is perfect I think.


Artificial blood substitutes are being researched and developed as alternatives for replacing RBCs for oxygen carrying capacity. Regular human blood has a shelf life of only 42 days which limits their utilization over more extended periods. This necessitates the development of blood substitutes which can be stored for longer duration. In addition, blood substitutes have universal compatibility, and therefore their application is not restricted by typing and cross-matching. Blood substitutes are extremely necessary in case of acute and chronic blood loss from injuries and accidents where a shortage of oxygen to cells affects the survival of patient by inflicting permanent damage to tissues.

Blood substitutes market is categorized into two segments viz. Perfluorocarbon-based oxygen carriers (PFBOC), and Hemoglobin-based oxygen carriers (HBOC). PFBOCs are based on inert components which replace hydrogen with fluorine. HBOCs consists of hemoglobin derived products sourced from humans blood, bovine blood, microorganisms and transgenic animals.


Artificial blood Substitute is an artificially developed substitute for red blood cells which is use for transporting oxygen and nutrients to the body cells and transporting back carbon dioxide, ammonia and other waste products away from cells.

Six potential application markets have been identified based on the possibility of replacing donor blood in critical medical treatments-

Injuries, Cardiovascular diseases, Malignant neoplasms, Neonatal Conditions, Organ transplants, Maternal condition


Some of the information contained in this post requires additional references. Please edit to add citations to reliable sources that support the assertions made here. Unsourced material may be disputed or deleted.

  • $\begingroup$ Welcome - The question is on antigens in specific and hence your answer doesn't address the question. Further, your answer is not references or supported by credible web links. -1 $\endgroup$ – AliceD Oct 17 '18 at 7:58

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