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诱导多能干细胞生成红细胞。

Generation of red blood cells from induced pluripotent stem cells.

机构信息

Division of Hematology, Department of Pediatrics.

Division of Transfusion Medicine, Department of Pathology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

出版信息

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

DOI:10.1097/MOH.0000000000000810
PMID:38362913
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10959681/
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.

摘要

目的综述

人诱导多能干细胞(iPSC)是一种有吸引力的来源,可以在体外产生用于输血和试剂红细胞的血液。我们综述了该领域的最新进展以及临床应用中仍然存在的局限性。

最近的发现

对于 iPSC 衍生的红细胞(RBC)生成,最近的工作已经优化了培养条件,以省略饲养细胞,增强红细胞成熟,并产生模拟胎儿或成人型 RBC 的细胞。基因组编辑提供了新的策略来提高细胞产量并创建具有定制抗原表型的设计 RBC。

总结

目前的方案支持模仿胚胎和胎儿造血的红细胞生成,并且细胞产量足以满足诊断 RBC 试剂的需求。为输血生成 RBC 仍然存在一些挑战,包括再现功能性成人型细胞的定型红细胞生成、增加培养条件的可扩展性以及优化高密度制造能力。

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本文引用的文献

1
Modeling primitive and definitive erythropoiesis with induced pluripotent stem cells.利用诱导多能干细胞进行原始和定向红细胞生成的建模。
Blood Adv. 2024 Mar 26;8(6):1449-1463. doi: 10.1182/bloodadvances.2023011708.
2
ABO gene editing for the conversion of blood type A to universal type O in Rh donor-derived human-induced pluripotent stem cells.ABO 基因编辑将 Rh 供体来源的人诱导多能干细胞中的血型 A 转换为通用型 O。
Clin Transl Med. 2022 Oct;12(10):e1063. doi: 10.1002/ctm2.1063.
3
The use of pluripotent stem cells to generate diagnostic tools for transfusion medicine.利用多能干细胞为输血医学生成诊断工具。
Blood. 2022 Oct 13;140(15):1723-1734. doi: 10.1182/blood.2022015883.
4
Expansion and differentiation of ex vivo cultured erythroblasts in scalable stirred bioreactors.体外培养的红细胞在可扩展搅拌式生物反应器中的扩增和分化。
Biotechnol Bioeng. 2022 Nov;119(11):3096-3116. doi: 10.1002/bit.28193. Epub 2022 Aug 5.
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Lessons learned from the COVID-19 pandemic blood supply crisis.从新冠疫情血液供应危机中吸取的教训。
J Hosp Med. 2022 Jul;17(7):574-576. doi: 10.1002/jhm.12843. Epub 2022 Jun 21.
6
Selection of O-negative induced pluripotent stem cell clones for high-density red blood cell production in a scalable perfusion bioreactor system.在可扩展的灌注生物反应器系统中,为高密度红细胞生产选择 O 阴性诱导多能干细胞克隆。
Cell Prolif. 2022 Aug;55(8):e13218. doi: 10.1111/cpr.13218. Epub 2022 Mar 15.
7
Erythropoietic properties of human induced pluripotent stem cells-derived red blood cells in immunodeficient mice.人诱导多能干细胞源性红细胞在免疫缺陷小鼠中的红细胞生成特性。
Am J Hematol. 2022 Feb 1;97(2):194-202. doi: 10.1002/ajh.26410. Epub 2021 Nov 24.
8
Generation of 'designer erythroblasts' lacking one or more blood group systems from CRISPR/Cas9 gene-edited human-induced pluripotent stem cells.利用 CRISPR/Cas9 基因编辑的人类诱导多能干细胞生成缺乏一种或多种血型系统的“设计红细胞”。
J Cell Mol Med. 2021 Oct;25(19):9340-9349. doi: 10.1111/jcmm.16872. Epub 2021 Sep 21.
9
BMI1 enables extensive expansion of functional erythroblasts from human peripheral blood mononuclear cells.BMI1 可使来自人外周血单个核细胞的功能性成红细胞大量扩增。
Mol Ther. 2021 May 5;29(5):1918-1932. doi: 10.1016/j.ymthe.2021.01.022. Epub 2021 Jan 21.
10
A Scalable Suspension Platform for Generating High-Density Cultures of Universal Red Blood Cells from Human Induced Pluripotent Stem Cells.一种可扩展的悬浮平台,用于从人诱导多能干细胞生成高密度的通用红细胞培养物。
Stem Cell Reports. 2021 Jan 12;16(1):182-197. doi: 10.1016/j.stemcr.2020.11.008. Epub 2020 Dec 10.