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A Pint of Hope: Developing a Shelf-Stable Blood Substitute

The accessibility and supply of blood is critical for trauma care and a range of life-threatening medical intervention scenarios — but what happens when someone needs blood and they’re nowhere near a blood bank?

Researchers at the Johns Hopkins Applied Physics Laboratory (APL) in Laurel, Maryland, are attacking that question with Human Erythrocytes Available for Reconstitution and Transfusion (HEART), a research initiative leveraging lab-made, stem-cell-derived red blood cells to investigate the viability and scalability of shelf-stable, lyophilized — or “freeze-dried” — red blood cells.

“We’re focusing our research around the idea that the best substitute for red blood cells is, well, red blood cells,” said Claire Bell, a senior molecular biologist at APL. “Our goal is to get there without blood donors.”

The accessibility of life-saving blood is a persistent concern for military leaders in considering care for the nation’s warfighters when they’re far from home.

“As we prepare for potential engagements anywhere in the world, a secure blood supply is a critical component of force readiness and resilience,” said Suzy Kennedy, APL’s program area manager for Warfighter Health and Readiness.

Blood Supply Challenges

From deployed military units to hospitals in rural communities or remote parts of the world, the potential for a shelf-stable and transfusion-safe blood substitute has far-reaching implications.

A pint of donated blood has a shelf life of about 42 days when stored at the right temperature, which means maintaining a supply of blood through a pipeline of continuous donations. Donors, significant medical infrastructure, and trained medical professionals are among the necessities to keep blood flowing to patients via blood banks.

In remote or austere environments, however, warfighters currently depend on walking blood banks — or their fellow troops — when there’s a need for immediate and life-saving transfusions. But even walking blood banks present logistical challenges, like requiring medical supplies, individuals trained in blood donation and transfusion, records of warfighter blood types, and infrastructure to safely store blood.

Military ships at sea, for example, may have adequate medical staff and cold storage but would constantly need to resupply blood from the warfighters onboard. And depending on the donor, providing a unit of blood can require rest and rehydration, potentially impacting the readiness of a critical team member.

But for small teams on covert orders or mass-casualty situations, maintaining a blood supply and transfusion infrastructure is untenable, potentially leaving injured service members without access to lifesaving trauma care on the front lines.

Taking a New Approach

APL’s researchers recognize the necessity of a blood substitute that can be safely and readily transfused anywhere, anytime, and with minimal supplies. After seeing multiple military agencies list “blood substitutes” among their top research priorities, Bell was ready to attack this challenge from a new angle.

“I saw all the interest in solving this problem, but few of the ideas were taking a predominantly biological approach,” she said. “So many before us took an engineering approach, some of which were not proven to be safe or effective.”

Bell secured initial funding for HEART through the Laboratory’s fiscal year 2024 Independent Research and Development (IRAD) program. That’s when biomedical engineer Corrine Fuller joined the effort — later securing financial investment to continue the team’s progress during fiscal year 2025.

Leveraging Stem Cells

Bell and Fuller’s biological approach to developing a blood substitute leverages O-negative stem cells and organoids — clumps of cells that behave like an organ. In this case, a bone-marrow-like organoid is developed to produce a supply of red blood cells.

The pair opted to use lab-produced red blood cells because of the hurdles associated with collecting red blood cells from humans.

“We want to be able to do this from start to finish inside a lab,” said Fuller.

Once red blood cells are produced in the lab, they’re packed with cryopreservatives and dehydrated, resulting in a powdery substance.

“What’s unique about this work is we are developing a specialized process for lyophilizing, or essentially ‘freeze-drying,’ the cells so that they don’t require continuous refrigeration,” said Fuller. “Our goal is to develop a product that’s shelf-stable and usable in an austere or remote environment.”

The powdery red blood cells, which still contain the proteins and sugars found naturally in blood, can later be rehydrated with sterile saline solution. The goal is to make this shelf-stable blood substitute safe and effective for universal donorship, or the equivalent to receiving a unit of O-negative blood from a blood bank.

Ultimately the HEART blood substitute would require only that warfighters or medical teams carry a small container of freeze-dried cells and saline solution to have the materials necessary for a life-saving blood transfusion.

“APL has the unique ability to look at problems differently and attack them with novel solutions,” said Paul Velez, chief scientist in APL’s Asymmetric Operations Sector. “To break through a challenge that historically has seemed impossible to solve but is of critical importance for our warfighters — that’s a sweet spot for APL.”

Scaling the Process

During the next phase of development, APL researchers will work on proving the scalability of HEART. Early results from the initial effort led to follow-on funding to fabricate, test, and characterize a bioreactor capable of producing erythrocyte-like cells from human stem cells.

Building on this process, the team has already designed a prototype bioreactor that demonstrates how the process could enable larger-scale production.

Efforts like HEART directly support the Department of War’s goal of strengthening biomanufacturing capabilities while reducing reliance on vulnerable supply chains.

“Blood is a precious resource in a combat environment and there is never enough of it. The survivability of trauma patients dramatically increases when they can receive a transfusion within 24 hours,” said Kennedy. “The work of HEART, if successful, would solve many of the logistical challenges with maintaining a viable blood supply anywhere the U.S. deploys its warfighters. It would be an absolute game changer.”