Key Barriers To Development of Artificial Red Blood Cells Overcome Interview with:

Allan Doctor, MD Pediatric Critical Care Medicine Professor of Pediatrics and (Associate) Biochemistry Washington University School of Medicine & Saint Louis Children’s Hospital St. Louis, Missouri

Dr. Allan Doctor

Allan Doctor, MD
Pediatric Critical Care Medicine
Professor of Pediatrics and (Associate) Biochemistry
Washington University School of Medicine &
Saint Louis Children’s Hospital
St. Louis, Missouri What is the background for this study? What are the main findings?

Response: Our research team has developed the first nanoscale artificial cells designed to emulate vital functions of natural red blood cells. If ultimately confirmed safe for use in humans, this nanotechnology-based product, called ‘ErythroMer’, could represent a new and innovative alternative to blood transfusions that would be especially valuable in situations where stored blood is needed, but difficult to obtain or use, such as in pre-hospital or battlefield settings. The artificial cells are designed to be freeze-dried, stored for extended periods at ambient temperatures, and simply reconstituted with water for immediate use.

This year, the National Academy of Sciences estimated that 30,000 civilian trauma deaths/year are preventable and of these, two-thirds arise from hemorrhage in the pre-hospital phase of care. One key goal for our team is to advance treatment for trauma victims or soldiers in austere environments by initiating resuscitation in the field, particularly when transport is prolonged. ErythroMer could be a blood substitute that medics carry in their pack and literally take it out, add water, and inject. 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.

Proof-of-concept studies in mice, conducted in partnership with Greg Hare, MD, PhD, an expert in rodent transfusion models at the University of Toronto, demonstrate that the ‘nano-cytes’ capture oxygen in the lungs and release it to tissues — the main function of red blood cells — in a pattern indistinguishable from that seen in a control group of mice injected with their own blood. In rats, ErythroMer effectively resuscitated animals in shock from controlled, acute loss of 40 percent of their blood volume.

The donut-shaped artificial cells are formulated with bio-synthetic nanotechnology in partnership with Dipanjan Pan, PhD, a synthetic chemist and bioengineer at the University of Illinois at Urbana-Champaign, and are about one-fiftieth the size of human red blood cells. A specifically crafted polymer lining encodes a control system that links ErythroMer’s oxygen binding behavior to tissue-specific changes in pH that blood cells encounter during circulation, thus enabling the ‘nano-cytes’ to effectively capture oxygen in the lungs (high pH) and then release it where most needed: in tissues with the greatest oxygen debt from shock (low pH). Tests show ErythroMer matches the oxygen capture/release characteristics of human red blood cells within 10 percent, a level the researchers say should be sufficient to stabilize bleeding patients until a blood transfusion can be obtained. What should readers take away from your report?

Response: So far, tests suggest ErythroMer has overcome key barriers that halted development of previous blood substitutes, including unintentional vasodilator molecule trapping, which restricts flow by narrowing blood vessels. Our team’s next steps are testing in larger animals, optimizing circulation time, metabolism and safety, scaling efficient production, and ultimately conducting in-human clinical trials.

If further testing goes well, we estimate ErythroMer could be ready for use by field medics and emergency responders within 10-12 years. What recommendations do you have for future research as a result of this study?

Response: It appears that a technical and design barrier thwarting blood substitute development may have been surmounted, primarily due significant lessons learned by the outstanding prior work in this field as well as the opportunity to apply recent advances in nano-fabrication and improved understanding of normal red blood cell physiology and oxygen transport. We are looking forward to other innovative ‘next-generation’ approaches to artificial cells that take a similar approach. Thank you for your contribution to the community.

Citation: Abstract presented at the 2016 ASH meeting December 2016

Erythromer (EM), a Nanoscale Bio-Synthetic Artificial Red Cell: Proof of Concept and In Vivo Efficacy Results

Dipanjan Pan, PhD1*, Stephen Rogers, PhD2*, Santosh Misra, PhD1*, Gururaja Vulugundam, PhD1*, Lisa Gazdzinski, MS3*, Albert Tsui, PhD3*, Nikhil Mistry, MS3*, Ahmed Said, MD, PhD2*, Philip Spinella, MD2*, Greg Hare, MD, PhD3,4*, Greg Lanza, MD, PhD5* and Allan Doctor, MD6*

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on December 5, 2016 by Marie Benz MD FAAD