A recent conference presentation on the artificial blood product ErythroMer has been doing the rounds in the press in the past few days. It sounds like the researchers involved have made meaningful progress towards overcoming many of the practical hurdles that have halted similar lines of work. You might take a look back in the Fight Aging! archives for a good open access review that covers many of the attempts to create nanoparticles and cell-like entities that can usefully augment the principal activities of red blood cells. There have been many more challenges in this line of work than might immediately spring to mind, and it makes for interesting reading. ErythroMer is a nanoparticle rather than cell based approach, which is the side of the house that I see as having the greatest potential to exceed present capabilities of our evolved blood and oxygen transport systems. So it is good to see progress on this front; it is most likely from blood substitute nanoparticles that future oxygenation enhancement technologies will arise, offering greater physical robustness and resilience to injury.
There are many lines of research that aim to produce some form of artificial blood, whether built on existing biochemistry and the mass production of cells or cell-like entities, or constructed from first principles as an oxygen-bearing nanoparticle of some form. Even narrowly effective forms of artificial blood with limited uses might nonetheless offer sizable benefits. For example, consider a form of nanoparticle that cannot be used in the long term, but can nonetheless efficiently carry oxygen: this can form the basis for a cost-effective substitute for the large amounts of blood used in trauma cases. Alternatively, a way to mass produce normal red blood cells with specific blood groups would do away with the need for the infrastructure of blood donation and thus make the whole business of banking blood much cheaper. Alternatively again, nanoparticles are much smaller than red blood cells, yet can be engineered to carry more oxygen than those blood cells. In cases of stroke, heart attack, or other ischemic injuries nanoparticles can delivery oxygen to areas that blood cells cannot reach, as well as increase the levels of oxygen reaching all tissues in the body. It isn't just a matter of therapies for the damaged, either. When thinking about enhancement of healthy physiology, something that is a little further out in the future, if today's best oxygen-carrying nanoparticles could be made safe for the long term, then when fully oxygenated an individual could undertake activity for thirty minutes or more without needing to breathe. Food for thought.
Researchers have developed the first artificial red blood cells designed to emulate vital functions of natural red blood cells. If confirmed safe for use in humans, the nanotechnology-based product could represent an innovative alternative to blood transfusions. The artificial cells, called ErythroMer, are designed to be freeze-dried, stored at ambient temperatures, and simply reconstituted with water when needed. Proof-of-concept studies in mice demonstrate that the artificial cells capture oxygen in the lungs and release it to tissues - the main functions of red blood cells - in a pattern that is indistinguishable from that seen in a control group of mice injected with their own blood. In rats, ErythroMer effectively resuscitated animals in shock following acute loss of 40 percent of their blood volume.
The donut-shaped artificial cells are formulated with nanotechnology and are about one-fiftieth the size of human red blood cells. A special lining encodes a control system that links ErythroMer oxygen binding to changes in blood pH, thus enhancing oxygen acquisition in the lungs and then dispensing oxygen in tissues with the greatest need. Tests show ErythroMer matches this vital oxygen binding feature of human red blood cells within 10 percent, a level the researchers say should be sufficient to stabilize a bleeding patient until a blood transfusion can be obtained. So far, tests suggest ErythroMer has overcome key barriers that halted development of previous blood substitutes, including efficacy and blood vessel narrowing. The team's next steps are testing in larger animals, ongoing safety assessment, optimizing pharmacokinetics, and ultimately conducting in-human clinical trials. The researchers are also pursuing methods for scaling up production. If further testing goes well, they estimate ErythroMer could be ready for use within 10-12 years.
4.5 million Americans receive blood transfusions each year, but human blood is limited by its supply and availability. under development, including Perfluorocarbon-Based Oxygen Carriers (PBOC) and Cell-Free Hemoglobin Based Carriers (HBOC), have mostly failed to preserve key physiologic functions of human blood cells. An effective artificial blood substitute will likely create and fulfill market demands for applications including hemorrhagic shock and emergency blood supplies. ErythroMer is a novel blood substitute composed of a patented nanobialys nanoparticle. Existing blood substitutes under development often trap nitric oxide unintentionally and fail to release oxygen in a context-specific manner. ErythroMer has multiple unique advantages by design: (1) Toroidal morphology resembling red blood cells; (2) Physiologic oxygen binding and release; (3) Simple system to inhibit hemoglobin auto-oxidation; (4) Limited nitric oxide sequestration; (5) Amenability to freeze-drying (lyophilization) and reconstitution. As a validation of these advantages, ErythroMer has been shown to demonstrate superior performance than other blood substitutes in a rodent model.
There is need for an artificial oxygen (O2) carrier for use when stored blood is unavailable or undesirable. To date, efforts to develop hemoglobin (Hb) based oxygen carriers (HBOCs) have failed, because of design flaws which do not preserve physiologic interactions of Hb with: O2 (they capture O2 in lungs, but do not release O2 effectively to tissue) and nitric oxide (NO) (they trap NO, causing vasoconstriction). ErythroMer design surmounts these weaknesses by: encapsulating Hb, controlling O2 capture/release with a novel 2,3-DPG shuttle and attenuating NO uptake through shell properties. The ErythroMer prototype has passed rigorous initial ex vivo and in vivo "proof of concept" testing and bench testing, which suggests this design surmounts prior challenges (by HBOCs) in emulating normal RBC physiologic interactions with O2 and NO. In models of major bleeding/anemia, ErythroMer reconstitutes normal hemodynamics and O2 delivery, observed at the system, tissue, and cellular level. ErythroMer potential for extended ambient dry storage has significant implications for portability and use. Next steps include formulation scaling, detailed study of pharmacokinetics, biodistribution and safety, as well as evaluation in large animal models of hemorrhagic shock.
View the full article at FightAging
