AABB2026: Turning One Donation Into Multiple Red Blood Cell Units

How would your practice change if antigen-defined red blood cells with consistent characteristics were available on demand? What if you could produce dozens of units from a single donation by a well-matched donor?

Long a blood banker’s dream, manufactured red blood cells are moving closer to U.S. clinical trials.

At Sunday’s “Key Advances in Biotherapies” Oral Abstract Session, Kyle Meetze, BS, MBA, chief operating officer of Safi Biotherapeutics Inc., shared how his team is working to make manufactured red blood cells a viable option for transfusion. Getting there, however, will require scaling up production, controlling costs and moving from preclinical research to human studies.

Scaling Up Production

Safi’s manufacturing process starts with hematopoietic progenitor cells from mobilized peripheral blood or cord blood. The team expands the cells and then differentiates them into red blood cells over approximately 21 days. Induced pluripotent stem cells could offer another source in the future.

The resulting product has a defined antigen profile, is free of pathogens and immune cells, and consists of uniformly young red blood cells. Just as importantly, the donor’s antigen profile carries through the manufacturing process.

To increase production, Safi is focusing on cell density rather than simply building bigger bioreactors. The company currently achieves cell densities of approximately 100 million cells per milliliter, yielding one to two units from a 10-liter bioreactor. The goal is to reach 500 million cells per milliliter and eventually produce one to two units per liter of bioreactor volume.

Meetze said the process has performed consistently across scales ranging from 50 milliliters to 10 liters. Safi has also transferred the process to a contract development and manufacturing organization.

The manufactured cells are predominantly reticulocytes, with approximately 85% achieving enucleation. The final product is filtered to remove cells that retain their nuclei.

Compared with donor red blood cells, the manufactured cells showed similar deformability and oxygen dissociation characteristics. They were somewhat stiffer, however, and contained approximately 20% more hemoglobin per cell.

Cryopreservation could offer another advantage. Meetze reported that more than 80% of manufactured cells could be recovered fully functional using a method that does not require dimethyl sulfoxide or glycerol. In preclinical in vivo studies conducted with collaborators at Emory University, refrigerated and cryopreserved manufactured cells performed broadly comparably to fresh donor cells.

A Match for Patients Who Need It Most

For patients who need repeated transfusions, finding compatible blood can be challenging. Manufactured red blood cells could help by making antigen-matched units available in larger quantities and maintaining a consistent antigen profile across transfusions, potentially reducing the risk of alloimmunization. Patients with sickle cell disease are among those who could benefit.

Cord blood-derived cells could also offer a source of red blood cells for neonatal transfusions. And because the manufactured cells can be cryopreserved, units could be stored for use when needed. Meetze also pointed to manufactured reagent red blood cells as a potential near-term application.

Next Steps

Turning that potential into a practical transfusion option will depend in part on cost. Safi’s model targets parity with donor blood, but that projection has not yet been validated in practice. Key cost drivers include cell density, culture media, expensive cytokines and growth factors, and the process of recovering cells after manufacturing.

The team also needs to determine the effective clinical dose. Meetze hypothesized that it could be smaller than a conventional unit of packed red blood cells, but clinical studies will be needed to establish the dose.

Safi hopes to initiate a clinical trial under an investigational new drug application in 2027. Meetze noted that the work has received substantial funding from the Defense Health Agency. Moving forward will also require reliable sources of mobilized peripheral blood and cord blood.