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Review
. 2024 May 1;31(3):115-121.
doi: 10.1097/MOH.0000000000000810. Epub 2024 Feb 13.

Generation of red blood cells from induced pluripotent stem cells

Affiliations
Review

Generation of red blood cells from induced pluripotent stem cells

Naomi Gunawardena et al. Curr Opin Hematol. .

Abstract

Purpose of review: Human induced pluripotent stem cells (iPSCs) are an attractive source to generate in-vitro-derived blood for use as transfusable and reagent red cells. We review recent advancements in the field and the remaining limitations for clinical use.

Recent findings: For iPSC-derived red blood cell (RBC) generation, recent work has optimized culture conditions to omit feeder cells, enhance red cell maturation, and produce cells that mimic fetal or adult-type RBCs. Genome editing provides novel strategies to improve cell yield and create designer RBCs with customized antigen phenotypes.

Summary: Current protocols support red cell production that mimics embryonic and fetal hematopoiesis and cell yield sufficient for diagnostic RBC reagents. Ongoing challenges to generate RBCs for transfusion include recapitulating definitive erythropoiesis to produce functional adult-type cells, increasing scalability of culture conditions, and optimizing high-density manufacturing capacity.

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Conflict of interest statement

Conflict of Interest: U.S. Patent Application No. 16/757,815, entitled “Engineered Red Blood Cells Having Rare Antigen Phenotypes” by Stella Chou and Connie Westhoff in the name of The Children’s Hospital of Philadelphia and New York Blood Center, Inc. (national stage entry of International Application No. PCT/US2018/057932); manuscript describes engineered red blood cells covered in patent application. The authors have no other competing interests to declare.

Figures

Figure 1.
Figure 1.. Current goals in producing iPSC-derived RBCs.
Ongoing research in the field includes increasing cell yield and cost efficiency (A), improving erythroid maturation (B), and studying in vivo maturation and survival of in vitro-derived RBCs from iPSCs (C).

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