AI Article Synopsis
- Red blood cell (RBC) production from human pluripotent stem cells (PSCs) shows promise for new therapies and research but faces challenges with low efficiency and proper maturation in culture.
- A new two-dimensional culture system using ferric citrate treatment enhances the generation of erythroblasts with high β-globin expression—crucial for functional RBCs.
- The mature erythroblasts demonstrate effective growth potential when injected in vivo, suggesting that ferric citrate facilitates better cell maturation and could lead to stable protocols for generating clinically useful RBCs.
Article Abstract
Red blood cell (RBC) generation from human pluripotent stem cells (PSCs) offers potential for innovative cell therapy in regenerative medicine as well as developmental studies. Ex vivo erythropoiesis from PSCs is currently limited by the low efficiency of functional RBCs with β-globin expression in culture systems. During induction of β-globin expression, the absence of a physiological microenvironment, such as a bone marrow niche, may impair cell maturation and lineage specification. Here, we describe a simple and reproducible culture system that can be used to generate erythroblasts with β-globin expression. We prepared a two-dimensional defined culture with ferric citrate treatment based on definitive hemogenic endothelium (HE). Floating erythroblasts derived from HE cells were primarily CD45CD71CD235a cells, and their number increased remarkably upon Fe treatment. Upon maturation, the erythroblasts cultured in the presence of ferric citrate showed high transcriptional levels of β-globin and enrichment of genes associated with heme synthesis and cell cycle regulation, indicating functionality. The rapid maturation of these erythroblasts into RBCs was observed when injected in vivo, suggesting the development of RBCs that were ready to grow. Hence, induction of β-globin expression may be explained by the effects of ferric citrate that promote cell maturation by binding with soluble transferrin and entering the cells.Taken together, upon treatment with Fe, erythroblasts showed advanced maturity with a high transcription of β-globin. These findings can help devise a stable protocol for the generation of clinically applicable RBCs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457393 | PMC |
| http://dx.doi.org/10.1038/s41536-023-00320-4 | DOI Listing |
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