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

Chad Tang, Andrew S. Lee, Jens Peter Volkmer, Debashis Sahoo, Divya Nag, Adriane R. Mosley, Matthew A. Inlay, Reza Ardehali, Shawn Chavez, Renee Reijo Pera, Barry Behr, Joseph C. Wu, Irving L. Weissman, Micha Drukker

Research output: Contribution to journalArticle

240 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)829-834
Number of pages6
JournalNature Biotechnology
Volume29
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Fingerprint

Stage-Specific Embryonic Antigens
Pluripotent Stem Cells
Teratoma
Antigens
Stem cells
Antibodies
Polysaccharides
Induced Pluripotent Stem Cells
Monoclonal antibodies
Microarray Analysis
Bioinformatics
Microarrays
Computational Biology
Sorting
Flow Cytometry
Fetus
Fluorescence
Immunohistochemistry
Monoclonal Antibodies
Cells

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Tang, C., Lee, A. S., Volkmer, J. P., Sahoo, D., Nag, D., Mosley, A. R., ... Drukker, M. (2011). An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nature Biotechnology, 29(9), 829-834. https://doi.org/10.1038/nbt.1947

An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. / Tang, Chad; Lee, Andrew S.; Volkmer, Jens Peter; Sahoo, Debashis; Nag, Divya; Mosley, Adriane R.; Inlay, Matthew A.; Ardehali, Reza; Chavez, Shawn; Pera, Renee Reijo; Behr, Barry; Wu, Joseph C.; Weissman, Irving L.; Drukker, Micha.

In: Nature Biotechnology, Vol. 29, No. 9, 09.2011, p. 829-834.

Research output: Contribution to journalArticle

Tang, C, Lee, AS, Volkmer, JP, Sahoo, D, Nag, D, Mosley, AR, Inlay, MA, Ardehali, R, Chavez, S, Pera, RR, Behr, B, Wu, JC, Weissman, IL & Drukker, M 2011, 'An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells', Nature Biotechnology, vol. 29, no. 9, pp. 829-834. https://doi.org/10.1038/nbt.1947
Tang, Chad ; Lee, Andrew S. ; Volkmer, Jens Peter ; Sahoo, Debashis ; Nag, Divya ; Mosley, Adriane R. ; Inlay, Matthew A. ; Ardehali, Reza ; Chavez, Shawn ; Pera, Renee Reijo ; Behr, Barry ; Wu, Joseph C. ; Weissman, Irving L. ; Drukker, Micha. / An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. In: Nature Biotechnology. 2011 ; Vol. 29, No. 9. pp. 829-834.
@article{aadf8819d3e84c92b81e18a92be0912f,
title = "An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells",
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.",
author = "Chad Tang and Lee, {Andrew S.} and Volkmer, {Jens Peter} and Debashis Sahoo and Divya Nag and Mosley, {Adriane R.} and Inlay, {Matthew A.} and Reza Ardehali and Shawn Chavez and Pera, {Renee Reijo} and Barry Behr and Wu, {Joseph C.} and Weissman, {Irving L.} and Micha Drukker",
year = "2011",
month = "9",
doi = "10.1038/nbt.1947",
language = "English (US)",
volume = "29",
pages = "829--834",
journal = "Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells

AU - Tang, Chad

AU - Lee, Andrew S.

AU - Volkmer, Jens Peter

AU - Sahoo, Debashis

AU - Nag, Divya

AU - Mosley, Adriane R.

AU - Inlay, Matthew A.

AU - Ardehali, Reza

AU - Chavez, Shawn

AU - Pera, Renee Reijo

AU - Behr, Barry

AU - Wu, Joseph C.

AU - Weissman, Irving L.

AU - Drukker, Micha

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052749542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052749542&partnerID=8YFLogxK

U2 - 10.1038/nbt.1947

DO - 10.1038/nbt.1947

M3 - Article

VL - 29

SP - 829

EP - 834

JO - Biotechnology

JF - Biotechnology

SN - 1087-0156

IS - 9

ER -