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Researchers develop artificial red blood cells for potential transfusion alternative
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SAN DIEGO — ErythroMer, a nanotechnology-based artificial red blood cell product, emulated normal red blood cell interactions with oxygen and nitric oxide, according to results of a proof-of-concept study presented at the ASH Annual Meeting and Exposition.
Once validated in human studies, this product could provide a life-saving alternative to blood transfusions for situations in which donated blood is scarce.
“One key goal is to advance field resuscitation of civilian trauma victims in remote settings and soldiers who are wounded in austere environments without access to timely evacuation,” Allan Doctor, MD, director of pediatric critical care medicine, professor of pediatrics and associate professor of biochemistry and molecular biophysics at Washington University in Saint Louis, said in a press release. “ErythroMer would be a blood substitute that a medic can carry in his or her pack and literally take it out, add water and inject it. There are currently no simple, practical means to bring transfusion to most trauma victims outside of hospitals. Delays in resuscitation significantly impact outcomes; it is our goal to push timely, effective care to field settings.”
Previous efforts to develop hemoglobin-based oxygen carriers for transfusion alternatives have failed due to two major flaws, Doctor said in a press conference.
These include “poor oxygen delivery to tissue, despite being able to improve oxygen content in the blood, and a problem with vasoconstriction, where the blood cells vasospasm, preventing traverse flow of normal red cells to tissue,” Doctor said. “Because of major improvements in synthetic chemistry and nanomedicine, we’ve been able to encapsulate normal human hemoglobin with a suite of small molecules that encode ‘wet wear’ that coordinate normal, or innovative, behavior for the particle that simulates red blood cells.”
Doctor and colleagues designed ErythroMer to encapsulate hemoglobin, control oxygen capture and release with a novel 2,3–DPG shuttle, and attenuate nitric oxide uptake through shell properties. The cells are designed to be freeze dried, stored at ambient temperatures and reconstituted with water when needed.
After 3 months of storage, researchers observe less than 10% change in size, zeta potential or polydispersity of the product.
Researchers tested the product in a hemorrhagic shock model in which 40% of blood volume was removed. One hour after resuscitation with an equal volume of ErythroMer or normal saline, models that received the experimental product achieved greater resolution of lactic acidosis (ErythroMer, 3.2 ± 1.5 mM vs. normal saline, 8.2 ± 2.1 mM), elevated arterial-venous oxygen difference (24 ± 11% vs. 67 ± 23%), and improved brain partial pressure oxygen (30.5 ± 1.4 Torr vs. 17.2 ± 1.3 Torr; P < .05 for all).
Researchers then conducted hemodilution models with pentastarch, fresh blood or ErythroMer. To detect whole body luciferase expression, researchers injected 50 mg/kg D-luciferin and obtained serial images. Results showed HIF–bioluminescence radiance was significantly greater in the pentastarch group than the fresh blood and ErythroMer groups (P < .01).
Based on these results, researchers next plan to evaluate formulation scaling, pharmacokinetics, biodistribution and safety, as well as conduct hemorrhagic shock models in larger animals.
ErythroMer could be ready to be used by field medics and emergency responders within 10 to 12 years, according to the researchers.
“We envision several opportunities for ErythroMer use outside the resuscitation of wounded soldiers and trauma victims,” Doctor said during the press conference. “ErythroMer possibly could be used for short term in the operating room, or to deliver oxygen in vascular obstruction, or to preserve viability of explanted organs prior to transplant.” – by Alexandra Todak
Reference:
Pan D, et al. Abstract 1027. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: Doctor reports equity ownership in KaloCyte and research funding from Children’s Discovery Institute and NIH. Please see the abstract for a list of all other researchers’ relevant financial disclosures.