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

被引：281

作者：

Tang, Chad ^{[1
]}

Lee, Andrew S. ^{[2
,3
]}

Volkmer, Jens-Peter ^{[1
,4
]}

Sahoo, Debashis ^{[1
]}

Nag, Divya ^{[2
,3
]}

Mosley, Adriane R. ^{[1
]}

Inlay, Matthew A. ^{[1
]}

Ardehali, Reza ^{[1
]}

Chavez, Shawn L. ^{[1
]}

Pera, Renee Reijo ^{[1
]}

Behr, Barry ^{[5
]}

Wu, Joseph C. ^{[2
,3
]}

Weissman, Irving L. ^{[1
]}

Drukker, Micha ^{[1
]}

机构：

[1] Stanford Univ Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA USA

[2] Stanford Univ Sch Med, Dept Radiol, Div Cardiol, Stanford, CA USA

[3] Stanford Univ Sch Med, Dept Med, Div Cardiol, Stanford, CA USA

[4] Univ Duesseldorf, Dept Urol, Dusseldorf, Germany

[5] Stanford Univ Sch Med, Dept Gynecol & Obstet, Stanford, CA USA

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 09期

关键词：

MONOCLONAL-ANTIBODY; CYTOTOXIC ANTIBODY; DIFFERENTIATION; ANTIGENS; STAGE; SURFACE; LINES; GLYCOSPHINGOLIPIDS; EXPRESSION; SERIES;

D O I：

10.1038/nbt.1947

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：829 / U86

页数：7

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