# Generation of cultured RBCs with rare phenotypes for transfusion from sources usually discarded during regular blood donations

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $423,750

## Abstract

Abstract
In developed countries, blood with rare phenotypes for alloimmunized patients is often unavailable. The use of
cultured RBCs (cRBCs) to address these clinical needs gained momentum when our laboratory, among others,
developed conditions for large scale production of cRBCs. Presently, several laboratories, including ours, are
addressing the numerous barriers to establish cRBCs as clinical product.
In 2011, the Douay laboratory demonstrated that 2.5x1010 autologous cRBCs (5 mL of blood) generated from
mobilized CD34pos cells have normal survival in vivo. However, this ground breaking study has four caveats: 1)
mobilization is unlikely to be accepted as procedure to generate cRBCs for clinical or diagnostic use, 2) the
amount of cRBCs generated (~5 mL of blood) is one-log lower than the minimal dose required to transfuse a
child (50 mL or 2.5x1011 RBCs), 3) normal volunteers are not ideal recipients for the first clinical trial to assess
efficacy, and 4) the high costs to produce the cRBC limit their clinical use as product.
This proposal will address these caveats by providing proof-of-principle that clinically useful doses of cRBCs
can be generated from discarded stem cell sources and used for transfusion of alloimmunized patients with
rare phenotypes for whom, having no alternatives, the costs to produce cRBCs is considered reasonable.
This proposal is based on a close collaboration among basic scientists (Drs. Migliaccio and Bieker, Icahn
School of Medicine and Mount Sinai) and clinicians (Drs. Klein and Flegel, Transfusion Medicine Department
of the NIH). These investigators will perform experiments aimed to establish whether leukoreduction by-
products currently discarded from regular blood donations with rare phenotypes are suitable to generate
2.5x1011 cRBCs (Aim 1) using novel culture strategies based on “gene editing” that will increase yields while
reducing production costs (Aim 2).
We believe that the documented previous colloboration between Drs Migliaccio and Bieker, as well as the two
new collaborators (Drs. Funnel and Zon), on scientific questions related to this application and the long
standing interest of Drs Klein and Flegel in clinical management of Sickle Cell Anemia patients, including those
with rare phenotypes, assures the synergistic development of scientific and clinical aspects of this proposal.
This is necessary to maximize the likelihood of efficiently producing adequate numbers of cRBCs well-suited
for the first-in-man allogenic transfusion.

## Key facts

- **NIH application ID:** 10188596
- **Project number:** 5R01HL134684-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** JAMES J BIEKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188596

## Citation

> US National Institutes of Health, RePORTER application 10188596, Generation of cultured RBCs with rare phenotypes for transfusion from sources usually discarded during regular blood donations (5R01HL134684-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10188596. Licensed CC0.

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