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针对人多能干细胞上 SSEA-5 聚糖的抗体可去除致瘤细胞。

An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells.

机构信息

Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.

出版信息

Nat Biotechnol. 2011 Aug 14;29(9):829-34. doi: 10.1038/nbt.1947.

DOI:10.1038/nbt.1947
PMID:21841799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3537836/
Abstract

An important risk in the clinical application of human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells (hESCs and hiPSCs), is teratoma formation by residual undifferentiated cells. We raised a monoclonal antibody against hESCs, designated anti-stage-specific embryonic antigen (SSEA)-5, which binds a previously unidentified antigen highly and specifically expressed on hPSCs--the H type-1 glycan. Separation based on SSEA-5 expression through fluorescence-activated cell sorting (FACS) greatly reduced teratoma-formation potential of heterogeneously differentiated cultures. To ensure complete removal of teratoma-forming cells, we identified additional pluripotency surface markers (PSMs) exhibiting a large dynamic expression range during differentiation: CD9, CD30, CD50, CD90 and CD200. Immunohistochemistry studies of human fetal tissues and bioinformatics analysis of a microarray database revealed that concurrent expression of these markers is both common and specific to hPSCs. Immunodepletion with antibodies against SSEA-5 and two additional PSMs completely removed teratoma-formation potential from incompletely differentiated hESC cultures.

摘要

人多能干细胞（hPSCs），包括人胚胎干细胞和诱导多能干细胞（hESCs 和 hiPSCs），在临床应用中存在一个重要风险，即残留未分化细胞会形成畸胎瘤。我们制备了一种针对 hESC 的单克隆抗体，命名为抗阶段特异性胚胎抗原-5（anti-SSEA-5），它可以高度特异性地识别 hPSCs 上表达的一种先前未知的抗原——H 型-1 糖。基于 SSEA-5 表达的通过荧光激活细胞分选（FACS）的分离极大地降低了异质分化培养物的畸胎瘤形成潜力。为了确保完全去除形成畸胎瘤的细胞，我们鉴定了另外一些在分化过程中具有较大动态表达范围的多能性表面标志物（PSMs）：CD9、CD30、CD50、CD90 和 CD200。对人胎儿组织的免疫组织化学研究和微阵列数据库的生物信息学分析表明，这些标志物的共同表达既常见又特异于 hPSCs。用针对 SSEA-5 和另外两个 PSMs 的抗体进行免疫耗竭，可完全去除不完全分化的 hESC 培养物中的畸胎瘤形成潜力。

相似文献

[1]
An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells.

Nat Biotechnol. 2011-8-14

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.

Stem Cell Reports. 2025-7-8

[2]
Glycosylation in Stem Cell Biology.

Handb Exp Pharmacol. 2025

[3]
EIF3D safeguards the homeostasis of key signaling pathways in human primed pluripotency.

Sci Adv. 2025-4-11

[4]
Terminal α1,2-fucosylation of glycosphingolipids by FUT1 is a key regulator in early cell-fate decisions.

EMBO Rep. 2024-10

[5]
Targeting the stage-specific embryonic antigen (SSEA)-0 tumor neoantigen.

Curr Trends Immunol. 2023

[6]
From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes.

Mol Cell Biochem. 2025-1

[7]
Progress in preclinical research on induced pluripotent stem cell therapy for acute myocardial infarction.

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024-4-25

[8]
Glycan Modifications as Regulators of Stem Cell Fate.

Biology (Basel). 2024-1-26

[9]
Label-Free and High-Throughput Removal of Residual Undifferentiated Cells From iPSC-Derived Spinal Cord Progenitor Cells.

Stem Cells Transl Med. 2024-4-15

[10]
Interconversion of Cancer Cells and Induced Pluripotent Stem Cells.

Cells. 2024-1-10

本文引用的文献

[1]
Potential barriers to therapeutics utilizing pluripotent cell derivatives: intrinsic immunogenicity of in vitro maintained and matured populations.

Semin Immunopathol. 2011-4-11

[2]
Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

Nature. 2010-7-1

[3]
MiDReG: a method of mining developmentally regulated genes using Boolean implications.

Proc Natl Acad Sci U S A. 2010-3-15

[4]
Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development.

Genes Dev. 2009-10-15

[5]
Effects of cell number on teratoma formation by human embryonic stem cells.

Cell Cycle. 2009-8-15

[6]
mAb 84, a cytotoxic antibody that kills undifferentiated human embryonic stem cells via oncosis.

Stem Cells. 2009-8

[7]
Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies.

Stem Cell Res. 2009-5

[8]
Boolean implication networks derived from large scale, whole genome microarray datasets.

Genome Biol. 2008-10-30

[9]
Complex N-glycans or core 1-derived O-glycans are not required for the expression of stage-specific antigens SSEA-1, SSEA-3, SSEA-4, or Le(Y) in the preimplantation mouse embryo.

Glycoconj J. 2009-4

[10]
Cell surface biomarkers of embryonic stem cells.

Proteomics. 2008-10

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