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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2022, Vol. 12 ›› Issue (02) : 115 -120. doi: 10.3877/cma.j.issn.2095-1221.2022.02.009

综述

人诱导性多能干细胞向红系分化的研究进展
陈妙纯1, 吴高椿2, 刘韬1,†()   
  1. 1. 515063　汕头，广东汕头大学医学院；518001　深圳市罗湖区人民医院　（深圳大学第三附属医院）肿瘤免疫科
    2. 518001　深圳市罗湖区人民医院　（深圳大学第三附属医院）肿瘤免疫科
  • 收稿日期:2021-12-08 出版日期:2022-04-01
  • 通信作者: 刘韬
  • 基金资助:
    深圳市科技创新委员会资助基础研究项目(JCYJ20170412155231633)

Research progress on erythroid differentiation of human induced pluripotent stem cells

Miaochun Chen1, Gaochun Wu2, Tao Liu1,†()   

  1. 1. Shantou University Medical College, Shantou 515063, China; Department of Tumor Immunotherapy, Shenzhen Luohu People's Hospital, the Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, China
    2. Department of Tumor Immunotherapy, Shenzhen Luohu People's Hospital, the Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, China
  • Received:2021-12-08 Published:2022-04-01
  • Corresponding author: Tao Liu
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引用本文：

陈妙纯, 吴高椿, 刘韬. 人诱导性多能干细胞向红系分化的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(02): 115-120.

Miaochun Chen, Gaochun Wu, Tao Liu. Research progress on erythroid differentiation of human induced pluripotent stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(02): 115-120.

红细胞输注对于重症贫血等血液病患者来说是主要的治疗手段，可以降低发病率和死亡率。目前红细胞来源主要依靠无偿献血，但是存在血液资源紧张、血型相容性（ABO和Rh抗原）和感染风险增加等挑战。体外诱导干细胞分化为成熟红细胞有望解决上述难题。人诱导性多能干细胞（iPSCs）具有无限增殖和多向分化能力，在体外经过定向诱导分化可以获得大量的红细胞，满足临床对红细胞的大量需求。本文将对人iPSCs向红系分化的技术发展和临床应用进行综述。

关键词: 红细胞输注, 诱导性多能干细胞, 红系分化, 临床应用

Red blood cell transfusion is the main treatment for patients with severe anemia and other hematological diseases, which can reduce morbidity and mortality. At present, the source of red blood cells mainly relies on voluntary blood donation, but there are challenges such as shortage of blood resources, blood group compatibility (ABO and Rh antigens) and increased risk of infection. Differentiation of stem cells into mature erythrocytes in vitro is expected to solve the above problems. Human induced pluripotent stem cells (iPSCs) have unlimited proliferation and multi-directional differentiation ability, and can obtain a large number of erythrocytes after directional induction and differentiation in vitro, meeting the clinical demand for erythrocytes. This article will review the technical development and clinical application of erythroid differentiation of human iPSCs.

Key words: Red blood cell transfusion, Induced pluripotent stem cells, Erythroid differentiation, Clinical application
表1 红系分化iPSCs的来源
来源 导入的转录因子 参考文献
人成纤维细胞 Oct4, Klf4, Sox2, LIN28 [25]
人肠道肠系膜 OCT4, SOX2, NANOG [26]
人羊膜 OCT4, SOX2, NANOG [27]
人牙龈成纤维细胞和牙周韧带成纤维细胞 OCT3/4, SOX2, KLF4, c-MYC [28]
人骨髓基质细胞 OCT3/4, SOX2, KLF4, c-MYC [29]
人脐带血 单独表达OCT4和SOX2 （CD34-2F-iPSC）或表达OCT4, SOX2, KLF4和c-MYC（CD34-4F-iPSC） [30]
人外周血 OCT4, SOX2, KLF4和MYC [31]
图1 iPSCs体外向红系分化过程[32]注：iPSCs为诱导性多能干细胞；HSCs为造血干细胞；BFU-E为红细胞爆式集落形成单位；CFU-E为红系集落形成单位；SCF为干细胞因子；IL-6为白细胞介素6；G-CSF为粒细胞集落刺激因子；VEGF为血管内皮生长因子；IL-3为白细胞介素3；EPO为促红细胞生成素；Flt3-l为FMS样酪氨酸激酶3配体；SCF为干细胞因子；TPO为血小板生成素；TGF-β为转化生长因子-β
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