An Optimized Human Erythroblast Differentiation System Reveals Cholesterol-Dependency of Robust Production of Cultured Red Blood Cells Ex Vivo

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2024 Mar 14

PMID 38481061

Authors

Enyu Wang

Senquan Liu

Xinye Zhang

Qingyou Peng

Huijuan Yu

Lei Gao

An Xie

Ding Ma

Gang Zhao

Linzhao Cheng

Affiliations

Soon will be listed here.

Abstract

The generation of cultured red blood cells (cRBCs) ex vivo represents a potentially unlimited source for RBC transfusion and other cell therapies. Human cRBCs can be generated from the terminal differentiation of proliferating erythroblasts derived from hematopoietic stem/progenitor cells or erythroid precursors in peripheral blood mononuclear cells. Efficient differentiation and maturation into cRBCs highly depend on replenishing human plasma, which exhibits variable potency across donors or batches and complicates the consistent cRBC production required for clinical translation. Hence, the role of human plasma in erythroblast terminal maturation is investigated and uncovered that 1) a newly developed cell culture basal medium mimicking the metabolic profile of human plasma enhances cell growth and increases cRBC yield upon erythroblast terminal differentiation and 2) LDL-carried cholesterol, as a substitute for human plasma, is sufficient to support erythroid survival and terminal differentiation ex vivo. Consequently, a chemically-defined optimized medium (COM) is developed, enabling robust generation of cRBCs from erythroblasts of multiple origins, with improved enucleation efficiency and higher reticulocyte yield, without the need for supplementing human plasma or serum. In addition, the results reveal the crucial role of lipid metabolism during human terminal erythropoiesis.

Citing Articles

Differentiating erythroblasts adapt to mechanical stimulation by upregulation of cholesterol biosynthesis via S1P/SREBP-induced HMGCR expression.

Iacono G, Abay A, Murillo J, Aglialoro F, Yagci N, Varga E Sci Rep. 2024; 14(1):30157.

PMID: 39627481 PMC: 11615233. DOI: 10.1038/s41598-024-81746-8.

An Optimized Human Erythroblast Differentiation System Reveals Cholesterol-Dependency of Robust Production of Cultured Red Blood Cells Ex Vivo.

Wang E, Liu S, Zhang X, Peng Q, Yu H, Gao L Adv Sci (Weinh). 2024; 11(22):e2303471.

PMID: 38481061 PMC: 11165465. DOI: 10.1002/advs.202303471.

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