Using Gene Editing to Establish a Safeguard System for Pluripotent Stem-Cell-Based Therapies

A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1...

Full description

Saved in:
Bibliographic Details
Published iniScience Vol. 22; pp. 409 - 422
Main Authors Wu, Youjun, Chang, Tammy, Long, Yan, Huang, He, Kandeel, Fouad, Yee, Jiing-Kuan
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 20.12.2019
Elsevier
Subjects
Cellular Therapy
Stem Cells Research
Techniques in Genetics
Stem Cells Research
Techniques in Genetics
Cellular Therapy
Online AccessGet full text

Cover

Abstract A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4, two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy. [Display omitted] •In-frame iC9 gene insertion into the SOX2 locus to target undifferentiated hESCs•The residual ESCs are selectively removed without affecting their differentiated progeny•Eradication of residual ESCs before transplantation provides an extra safety control Cellular Therapy; Techniques in Genetics; Stem Cells Research
AbstractList A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4, two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy.
A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4, two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy. [Display omitted] •In-frame iC9 gene insertion into the SOX2 locus to target undifferentiated hESCs•The residual ESCs are selectively removed without affecting their differentiated progeny•Eradication of residual ESCs before transplantation provides an extra safety control Cellular Therapy; Techniques in Genetics; Stem Cells Research
A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4, two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy. : Cellular Therapy; Techniques in Genetics; Stem Cells Research Subject Areas: Cellular Therapy, Techniques in Genetics, Stem Cells Research
A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4, two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy.A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9, into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4, two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy.
A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells. We used CRISPR-Cas9 for in-frame insertion of a suicide gene, iC9 , into the endogenous SOX2 locus in human embryonic stem cell (ESC) line H1 for specific eradication of undifferentiated cells without affecting differentiated cells. This locus was chosen over NANOG and OCT4 , two other well-characterized stem cell loci, due to significantly reduced off-target effect. We showed that undifferentiated H1-iC9 cells were induced to apoptosis by iC9 inducer AP1903, whereas differentiated cell lineages including hematopoietic cells, neurons, and islet beta-like cells were not affected. We also showed that AP1903 selectively removed undifferentiated H1-iC9 cells from a mixed cell population. This strategy therefore provides a layer of safety control before transplantation of a stem-cell-derived product in therapy. • In-frame iC9 gene insertion into the SOX2 locus to target undifferentiated hESCs • The residual ESCs are selectively removed without affecting their differentiated progeny • Eradication of residual ESCs before transplantation provides an extra safety control Cellular Therapy; Techniques in Genetics; Stem Cells Research
Author Yee, Jiing-Kuan
Long, Yan
Huang, He
Chang, Tammy
Kandeel, Fouad
Wu, Youjun
AuthorAffiliation 2 Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310027, China
1 Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
AuthorAffiliation_xml – name: 1 Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
– name: 2 Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310027, China
Author_xml – sequence: 1
  givenname: Youjun
  surname: Wu
  fullname: Wu, Youjun
  organization: Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
– sequence: 2
  givenname: Tammy
  surname: Chang
  fullname: Chang, Tammy
  organization: Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
– sequence: 3
  givenname: Yan
  surname: Long
  fullname: Long, Yan
  organization: Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
– sequence: 4
  givenname: He
  surname: Huang
  fullname: Huang, He
  organization: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310027, China
– sequence: 5
  givenname: Fouad
  surname: Kandeel
  fullname: Kandeel, Fouad
  organization: Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
– sequence: 6
  givenname: Jiing-Kuan
  surname: Yee
  fullname: Yee, Jiing-Kuan
  email: jyee@coh.org
  organization: Departments of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31821946$$D View this record in MEDLINE/PubMed
BookMark eNp9Ul1LHDEUDWKpVv0DPpQ89mXGfMzMJlAKddmqIFRYfSuETHJnN8vsZJtkBP99M10t2gchkOTmnHNz7z2f0OHgB0DonJKSEtpcbEoXjSsZobKktCRcHKBjVgtZEFKxw1fnI3QW44YQwvKqZPMRHXEqGJVVc4x-PUQ3rPAVDIAX1qXpkjxexKTb3sU11nipO1iNOli8fIoJtrjzAd_1Y3A7n2BIeJmDxRz6vrjUESy-X0PQOwfxFH3odB_h7Hk_QQ8_Fvfz6-L259XN_PttYWoxSwWrSS2tITNT1S3IlopOiqo1jMnKaqFnAjiRgrZtyzsrRMNlw2nT0IYICZ3lJ-hmr2u93qhdcFsdnpTXTv0N-LBSOiRnelCGclYDM7kmU9nOyHaW-yKktqaDqhZZ69teaze2W7AmFxh0_0b07cvg1mrlH1UjiSSkzgJfngWC_z1CTGqbJ5W7owfwY1SM5yHk3wueoZ9f5_qX5GU8GSD2ABN8jAE6ZVzSyfkptesVJWoyg9qoyQxqMoOiVGUzZCr7j_qi_i7p654EeVqPDoLKCBgMWBfApNxO9x79D_M3ze8
CitedBy_id crossref_primary_10_1134_S0006297924050031
crossref_primary_10_3390_ijms222111321
crossref_primary_10_31857_S0320972524050036
crossref_primary_10_1093_pcmedi_pbac004
crossref_primary_10_22289_2446_922X_V10S1A8
crossref_primary_10_1111_cpr_13248
crossref_primary_10_1038_s41467_020_16455_7
crossref_primary_10_1016_j_trsl_2022_06_014
crossref_primary_10_3390_ijms22189991
crossref_primary_10_1038_s41598_021_81351_z
crossref_primary_10_1007_s13238_021_00831_0
crossref_primary_10_1016_j_molmet_2022_101477
crossref_primary_10_1002_sctm_21_0135
crossref_primary_10_1016_j_omtm_2021_03_002
crossref_primary_10_1016_j_mmm_2023_05_009
crossref_primary_10_3389_fendo_2021_631463
crossref_primary_10_1016_j_omtm_2022_01_014
Cites_doi 10.1016/j.stemcr.2019.01.012
10.1002/stem.2428
10.1038/nprot.2008.146
10.1016/j.stemcr.2015.04.016
10.1016/S0021-9258(19)47263-3
10.1038/mtm.2014.53
10.1038/s41586-019-1168-5
10.7554/eLife.40167
10.1016/j.scr.2009.02.002
10.1038/s41586-018-0733-7
10.1038/mt.2015.100
10.1126/science.275.5303.1129
10.1016/j.scr.2017.07.006
10.1126/science.276.5319.1719
10.1371/journal.pone.0114275
10.1016/S0092-8674(02)00835-8
10.1038/nbt.3033
10.1016/j.cell.2013.08.021
10.1038/nature06046
10.1089/clo.2004.6.217
10.1128/JVI.01865-08
10.1016/j.stemcr.2015.04.005
10.1126/science.282.5391.1145
10.1073/pnas.95.18.10437
10.1038/nbt.1562
10.1016/j.cell.2014.09.040
10.1016/j.biomaterials.2012.01.023
10.1038/nbt.1788
10.1371/journal.pone.0081131
10.1016/j.jacc.2017.11.047
10.1021/acschembio.8b00490
10.1634/stemcells.21-3-257
10.1073/pnas.1303669110
10.1074/jbc.M702969200
10.1016/S0140-6736(14)61376-3
10.1038/nrm2308
10.1126/science.278.5345.1966
10.4161/org.24317
10.1016/j.lfs.2015.12.023
10.1023/A:1024116916932
10.1093/nar/gkm059
10.1182/blood-2004-11-4564
10.1242/dev.003855
10.1634/stemcells.2007-0951
10.1016/S0896-6273(03)00497-5
10.1073/pnas.1115201109
10.1182/blood-2005-03-0987
ContentType Journal Article
Copyright 2019 The Authors
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
2019 The Authors 2019
Copyright_xml – notice: 2019 The Authors
– notice: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
– notice: 2019 The Authors 2019
DBID 6I.
AAFTH
AAYXX
CITATION
NPM
7X8
5PM
DOA
DOI 10.1016/j.isci.2019.11.038
DatabaseName ScienceDirect Open Access Titles
Elsevier:ScienceDirect:Open Access
CrossRef
PubMed
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
PubMed
MEDLINE - Academic
DatabaseTitleList PubMed


MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
EISSN 2589-0042
EndPage 422
ExternalDocumentID oai_doaj_org_article_c1325e2cafec4dfc9b702089adcfe458
PMC6909005
31821946
10_1016_j_isci_2019_11_038
S2589004219304894
Genre Journal Article
GroupedDBID 0SF
53G
6I.
AACTN
AAEDW
AAFTH
AALRI
AAXUO
ABMAC
ADBBV
AEXQZ
AFTJW
AITUG
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
AOIJS
BCNDV
EBS
FDB
GROUPED_DOAJ
HYE
M41
NCXOZ
OK1
ROL
RPM
SSZ
0R~
AAMRU
AAYWO
AAYXX
ACVFH
ADCNI
ADVLN
AEUPX
AFPUW
AIGII
AKBMS
AKYEP
APXCP
CITATION
EJD
NPM
7X8
5PM
ID FETCH-LOGICAL-c587t-25059dc07c45be9b18f984bc2294da8a78e30981bbb3fd886396316616089efd3
IEDL.DBID DOA
ISSN 2589-0042
IngestDate Wed Aug 27 01:27:26 EDT 2025
Thu Aug 21 18:29:48 EDT 2025
Fri Jul 11 12:35:06 EDT 2025
Thu Apr 03 06:59:02 EDT 2025
Tue Jul 01 01:03:27 EDT 2025
Thu Apr 24 23:10:03 EDT 2025
Wed May 17 00:04:01 EDT 2023
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords Stem Cells Research
Techniques in Genetics
Cellular Therapy
Language English
License This is an open access article under the CC BY-NC-ND license.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c587t-25059dc07c45be9b18f984bc2294da8a78e30981bbb3fd886396316616089efd3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Lead Contact
OpenAccessLink https://doaj.org/article/c1325e2cafec4dfc9b702089adcfe458
PMID 31821946
PQID 2324916683
PQPubID 23479
PageCount 14
ParticipantIDs doaj_primary_oai_doaj_org_article_c1325e2cafec4dfc9b702089adcfe458
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6909005
proquest_miscellaneous_2324916683
pubmed_primary_31821946
crossref_citationtrail_10_1016_j_isci_2019_11_038
crossref_primary_10_1016_j_isci_2019_11_038
elsevier_sciencedirect_doi_10_1016_j_isci_2019_11_038
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2019-12-20
PublicationDateYYYYMMDD 2019-12-20
PublicationDate_xml – month: 12
  year: 2019
  text: 2019-12-20
  day: 20
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle iScience
PublicationTitleAlternate iScience
PublicationYear 2019
Publisher Elsevier Inc
Elsevier
Publisher_xml – name: Elsevier Inc
– name: Elsevier
References Graham, Khudyakov, Ellis, Pevny (bib13) 2003; 39
Hentze, Soong, Wang, Phillips, Putti, Dunn (bib15) 2009; 2
Caserta, Smith, Gultice, Reedy, Brown (bib5) 2003; 8
Yagyu, Hoyos, Del Bufalo, Brenner (bib45) 2015; 23
Lee, Moon, Jeong, Yi, Lee, Shim, Rhee, Lee, Oh, Lee (bib21) 2013; 110
Li, Xiang (bib22) 2013; 9
Thomson, Itskovitz-Eldor, Shapiro, Waknitz, Swiergiel, Marshall, Jones (bib41) 1998; 282
Liang, Monetti, Shutova, Neely, Hacibekiroglu, Yang, Kim, Zhang, Li, Nagy (bib23) 2018; 563
Reardon (bib33) 1989; 264
Rampoldi, Crooke, Preininger, Jha, Maxwell, Ding, Spearman, Finn, Xu (bib31) 2018; 13
Zhu, Verma, Gonzalez, Shi, Huangfu (bib49) 2015; 4
Qadir, Alvarez-Cubela, Belle, Sapir, Messaggio, Johnson, Umland, Hardin, Klein, Perez-Alvarez (bib29) 2019; 12
Youle, Strasser (bib47) 2008; 9
Cheng, Kirsch, Clem, Ravi, Kastan, Bedi, Ueno, Hardwick (bib7) 1997; 278
Que, Okubo, Goldenring, Nam, Kurotani, Morrisey, Taranova, Pevny, Hogan (bib30) 2007; 134
Wu, Hong, Winkler, Spencer, Jares, Ichwan, Nicolae, Guo, Larochelle, Dunbar (bib44) 2014; 1
Ou, Li, Reiser (bib27) 2013; 8
Schwartz, Regillo, Lam, Eliott, Rosenfeld, Gregori, Hubschman, Davis, Heilwell, Spirn (bib37) 2015; 385
Boer, Kopp, Mallanna, Desler, Chakravarthy, Wilder, Bernadt, Rizzino (bib2) 2007; 35
Santamaria, Barriere, Cerqueira, Hunt, Tardy, Newton, Caceres, Dubus, Malumbres, Barbacid (bib35) 2007; 448
Zarogoulidis, Darwiche, Sakkas, Yarmus, Huang, Li, Freitag, Zarogoulidis, Malecki (bib48) 2013; 4
LeBlanc, Lee, Yu, Kim, Kambhampati, Dupont, Seruggia, Ryu, Orkin, Kim (bib20) 2018; 7
Ng, Davis, Azzola, Stanley, Elefanty (bib26) 2005; 106
Davis, Costa, Grandela, Holland, Hatzistavrou, Micallef, Li, Goulburn, Azzola, Elefanty (bib11) 2008; 3
Balboa, Weltner, Novik, Eurola, Wartiovaara, Otonkoski (bib1) 2017; 23
Straathof, Pule, Yotnda, Dotti, Vanin, Brenner, Heslop, Spencer, Rooney (bib39) 2005; 105
Schuldiner, Itskovitz-Eldor, Benvenisty (bib36) 2003; 21
Pagliuca, Millman, Gurtler, Segel, Van Dervort, Ryu, Peterson, Greiner, Melton (bib28) 2014; 159
Song, Park, Kim, Lee, Choi, Chong, Shim, Del Priore, Lanza (bib38) 2015; 4
Green, Chen, Nostro, d'Souza, Schaniel, Lemischka, Gouon-Evans, Keller, Snoeck (bib14) 2011; 29
Klimanskaya, Hipp, Rezai, West, Atala, Lanza (bib17) 2004; 6
Bokhoven, Stephen, Knight, Gevers, Robinson, Takeuchi, Collins (bib3) 2009; 83
Davenport, Diekmann, Budde, Detering, Naujok (bib10) 2016; 34
Menasche, Vanneaux, Hagege, Bel, Cholley, Parouchev, Cacciapuoti, Al-Daccak, Benhamouda, Blons (bib24) 2018; 71
Talkhabi, Aghdami, Baharvand (bib40) 2016; 145
Kopp, Ormsbee, Desler, Rizzino (bib18) 2008; 26
Krentz, Nian, Lynn (bib19) 2014; 9
Wichterle, Lieberam, Porter, Jessell (bib43) 2002; 110
Ran, Hsu, Lin, Gootenberg, Konermann, Trevino, Scott, Inoue, Matoba, Zhang (bib32) 2013; 154
Rezania, Bruin, Arora, Rubin, Batushansky, Asadi, O'Dwyer, Quiskamp, Mojibian, Albrecht (bib34) 2014; 32
Chen, Guerrero, Huang, Shabier, Pan, Tan, Wang (bib6) 2007; 282
Moolten (bib25) 1986; 46
Yang, Liu, Bhalla, Kim, Ibrado, Cai, Peng, Jones, Wang (bib46) 1997; 275
Cheng, Ke, Chen, Cai, Gao, Ye, Wang, Zhang, Lahn, Li (bib8) 2012; 33
Veres, Faust, Bushnell, Engquist, Kenty, Harb, Poh, Sintov, Gurtler, Pagliuca (bib42) 2019; 569
Diril, Ratnacaram, Padmakumar, Du, Wasser, Coppola, Tessarollo, Kaldis (bib12) 2012; 109
Hockemeyer, Soldner, Beard, Gao, Mitalipova, DeKelver, Katibah, Amora, Boydston, Zeitler (bib16) 2009; 27
Clackson, Yang, Rozamus, Hatada, Amara, Rollins, Stevenson, Magari, Wood, Courage (bib9) 1998; 95
Bonini, Ferrari, Verzeletti, Servida, Zappone, Ruggieri, Ponzoni, Rossini, Mavilio, Traversari (bib4) 1997; 276
Ng (10.1016/j.isci.2019.11.038_bib26) 2005; 106
Thomson (10.1016/j.isci.2019.11.038_bib41) 1998; 282
Kopp (10.1016/j.isci.2019.11.038_bib18) 2008; 26
Schwartz (10.1016/j.isci.2019.11.038_bib37) 2015; 385
Clackson (10.1016/j.isci.2019.11.038_bib9) 1998; 95
Que (10.1016/j.isci.2019.11.038_bib30) 2007; 134
Wichterle (10.1016/j.isci.2019.11.038_bib43) 2002; 110
Klimanskaya (10.1016/j.isci.2019.11.038_bib17) 2004; 6
Talkhabi (10.1016/j.isci.2019.11.038_bib40) 2016; 145
Davenport (10.1016/j.isci.2019.11.038_bib10) 2016; 34
Rezania (10.1016/j.isci.2019.11.038_bib34) 2014; 32
Straathof (10.1016/j.isci.2019.11.038_bib39) 2005; 105
Green (10.1016/j.isci.2019.11.038_bib14) 2011; 29
Caserta (10.1016/j.isci.2019.11.038_bib5) 2003; 8
Zhu (10.1016/j.isci.2019.11.038_bib49) 2015; 4
Diril (10.1016/j.isci.2019.11.038_bib12) 2012; 109
Lee (10.1016/j.isci.2019.11.038_bib21) 2013; 110
Pagliuca (10.1016/j.isci.2019.11.038_bib28) 2014; 159
Liang (10.1016/j.isci.2019.11.038_bib23) 2018; 563
Qadir (10.1016/j.isci.2019.11.038_bib29) 2019; 12
Menasche (10.1016/j.isci.2019.11.038_bib24) 2018; 71
Ran (10.1016/j.isci.2019.11.038_bib32) 2013; 154
Ou (10.1016/j.isci.2019.11.038_bib27) 2013; 8
Wu (10.1016/j.isci.2019.11.038_bib44) 2014; 1
Zarogoulidis (10.1016/j.isci.2019.11.038_bib48) 2013; 4
Hockemeyer (10.1016/j.isci.2019.11.038_bib16) 2009; 27
Schuldiner (10.1016/j.isci.2019.11.038_bib36) 2003; 21
Krentz (10.1016/j.isci.2019.11.038_bib19) 2014; 9
Cheng (10.1016/j.isci.2019.11.038_bib8) 2012; 33
Bokhoven (10.1016/j.isci.2019.11.038_bib3) 2009; 83
Li (10.1016/j.isci.2019.11.038_bib22) 2013; 9
Reardon (10.1016/j.isci.2019.11.038_bib33) 1989; 264
Chen (10.1016/j.isci.2019.11.038_bib6) 2007; 282
Santamaria (10.1016/j.isci.2019.11.038_bib35) 2007; 448
Davis (10.1016/j.isci.2019.11.038_bib11) 2008; 3
Boer (10.1016/j.isci.2019.11.038_bib2) 2007; 35
Cheng (10.1016/j.isci.2019.11.038_bib7) 1997; 278
Veres (10.1016/j.isci.2019.11.038_bib42) 2019; 569
Hentze (10.1016/j.isci.2019.11.038_bib15) 2009; 2
Yang (10.1016/j.isci.2019.11.038_bib46) 1997; 275
Youle (10.1016/j.isci.2019.11.038_bib47) 2008; 9
LeBlanc (10.1016/j.isci.2019.11.038_bib20) 2018; 7
Yagyu (10.1016/j.isci.2019.11.038_bib45) 2015; 23
Moolten (10.1016/j.isci.2019.11.038_bib25) 1986; 46
Balboa (10.1016/j.isci.2019.11.038_bib1) 2017; 23
Bonini (10.1016/j.isci.2019.11.038_bib4) 1997; 276
Song (10.1016/j.isci.2019.11.038_bib38) 2015; 4
Rampoldi (10.1016/j.isci.2019.11.038_bib31) 2018; 13
Graham (10.1016/j.isci.2019.11.038_bib13) 2003; 39
References_xml – volume: 154
  start-page: 1380
  year: 2013
  end-page: 1389
  ident: bib32
  article-title: Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
  publication-title: Cell
– volume: 105
  start-page: 4247
  year: 2005
  end-page: 4254
  ident: bib39
  article-title: An inducible caspase 9 safety switch for T-cell therapy
  publication-title: Blood
– volume: 569
  start-page: 368
  year: 2019
  end-page: 373
  ident: bib42
  article-title: Charting cellular identity during human in vitro beta-cell differentiation
  publication-title: Nature
– volume: 145
  start-page: 98
  year: 2016
  end-page: 113
  ident: bib40
  article-title: Human cardiomyocyte generation from pluripotent stem cells: a state-of-art
  publication-title: Life Sci.
– volume: 13
  start-page: 2329
  year: 2018
  end-page: 2338
  ident: bib31
  article-title: Targeted elimination of tumorigenic human pluripotent stem cells using suicide-inducing virus-like particles
  publication-title: ACS Chem. Biol.
– volume: 275
  start-page: 1129
  year: 1997
  end-page: 1132
  ident: bib46
  article-title: Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked
  publication-title: Science
– volume: 34
  start-page: 2635
  year: 2016
  end-page: 2647
  ident: bib10
  article-title: Anterior-posterior patterning of definitive endoderm generated from human embryonic stem cells depends on the differential signaling of retinoic acid, Wnt-, and BMP-signaling
  publication-title: Stem Cells
– volume: 8
  start-page: e81131
  year: 2013
  ident: bib27
  article-title: Targeting of herpes simplex virus 1 thymidine kinase gene sequences into the OCT4 locus of human induced pluripotent stem cells
  publication-title: PLoS One
– volume: 9
  start-page: 34
  year: 2013
  end-page: 39
  ident: bib22
  article-title: Safeguarding clinical translation of pluripotent stem cells with suicide genes
  publication-title: Organogenesis
– volume: 39
  start-page: 749
  year: 2003
  end-page: 765
  ident: bib13
  article-title: SOX2 functions to maintain neural progenitor identity
  publication-title: Neuron
– volume: 33
  start-page: 3195
  year: 2012
  end-page: 3204
  ident: bib8
  article-title: Protecting against wayward human induced pluripotent stem cells with a suicide gene
  publication-title: Biomaterials
– volume: 32
  start-page: 1121
  year: 2014
  end-page: 1133
  ident: bib34
  article-title: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
  publication-title: Nat. Biotechnol.
– volume: 6
  start-page: 217
  year: 2004
  end-page: 245
  ident: bib17
  article-title: Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics
  publication-title: Cloning Stem Cells
– volume: 110
  start-page: E3281
  year: 2013
  end-page: E3290
  ident: bib21
  article-title: Inhibition of pluripotent stem cell-derived teratoma formation by small molecules
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 106
  start-page: 1601
  year: 2005
  end-page: 1603
  ident: bib26
  article-title: Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation
  publication-title: Blood
– volume: 4
  start-page: 1103
  year: 2015
  end-page: 1111
  ident: bib49
  article-title: A CRISPR/Cas-Mediated selection-free knockin strategy in human embryonic stem cells
  publication-title: Stem Cell Reports
– volume: 1
  start-page: 14053
  year: 2014
  ident: bib44
  article-title: Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies
  publication-title: Mol. Ther. Methods Clin. Dev.
– volume: 2
  start-page: 198
  year: 2009
  end-page: 210
  ident: bib15
  article-title: Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies
  publication-title: Stem Cell Res.
– volume: 7
  start-page: e40167
  year: 2018
  ident: bib20
  article-title: Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation
  publication-title: Elife
– volume: 563
  start-page: 701
  year: 2018
  end-page: 704
  ident: bib23
  article-title: Linking a cell-division gene and a suicide gene to define and improve cell therapy safety
  publication-title: Nature
– volume: 278
  start-page: 1966
  year: 1997
  end-page: 1968
  ident: bib7
  article-title: Conversion of Bcl-2 to a Bax-like death effector by caspases
  publication-title: Science
– volume: 282
  start-page: 33888
  year: 2007
  end-page: 33895
  ident: bib6
  article-title: Caspase-9-induced mitochondrial disruption through cleavage of anti-apoptotic BCL-2 family members
  publication-title: J. Biol. Chem.
– volume: 282
  start-page: 1145
  year: 1998
  end-page: 1147
  ident: bib41
  article-title: Embryonic stem cell lines derived from human blastocysts
  publication-title: Science
– volume: 3
  start-page: 1550
  year: 2008
  end-page: 1558
  ident: bib11
  article-title: A protocol for removal of antibiotic resistance cassettes from human embryonic stem cells genetically modified by homologous recombination or transgenesis
  publication-title: Nat. Protoc.
– volume: 9
  start-page: 47
  year: 2008
  end-page: 59
  ident: bib47
  article-title: The BCL-2 protein family: opposing activities that mediate cell death
  publication-title: Nat. Rev. Mol. Cell Biol.
– volume: 159
  start-page: 428
  year: 2014
  end-page: 439
  ident: bib28
  article-title: Generation of functional human pancreatic beta cells in vitro
  publication-title: Cell
– volume: 134
  start-page: 2521
  year: 2007
  end-page: 2531
  ident: bib30
  article-title: Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm
  publication-title: Development
– volume: 385
  start-page: 509
  year: 2015
  end-page: 516
  ident: bib37
  article-title: Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies
  publication-title: Lancet
– volume: 35
  start-page: 1773
  year: 2007
  end-page: 1786
  ident: bib2
  article-title: Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes
  publication-title: Nucleic Acids Res.
– volume: 23
  start-page: 105
  year: 2017
  end-page: 108
  ident: bib1
  article-title: Generation of an OCT4 reporter human induced pluripotent stem cell line using CRISPR/SpCas9
  publication-title: Stem Cell Res.
– volume: 23
  start-page: 1475
  year: 2015
  end-page: 1485
  ident: bib45
  article-title: An inducible caspase-9 suicide gene to improve the safety of therapy using human induced pluripotent stem cells
  publication-title: Mol. Ther.
– volume: 110
  start-page: 385
  year: 2002
  end-page: 397
  ident: bib43
  article-title: Directed differentiation of embryonic stem cells into motor neurons
  publication-title: Cell
– volume: 27
  start-page: 851
  year: 2009
  end-page: 857
  ident: bib16
  article-title: Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
  publication-title: Nat. Biotechnol.
– volume: 9
  start-page: e114275
  year: 2014
  ident: bib19
  article-title: TALEN/CRISPR-mediated eGFP knock-in add-on at the OCT4 locus does not impact differentiation of human embryonic stem cells towards endoderm
  publication-title: PLoS One
– volume: 4
  start-page: 16849
  year: 2013
  ident: bib48
  article-title: Suicide gene therapy for cancer - current strategies
  publication-title: J. Genet. Syndr. Gene Ther.
– volume: 95
  start-page: 10437
  year: 1998
  end-page: 10442
  ident: bib9
  article-title: Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 71
  start-page: 429
  year: 2018
  end-page: 438
  ident: bib24
  article-title: Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic Left ventricular dysfunction
  publication-title: J. Am. Coll. Cardiol.
– volume: 276
  start-page: 1719
  year: 1997
  end-page: 1724
  ident: bib4
  article-title: HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia
  publication-title: Science
– volume: 21
  start-page: 257
  year: 2003
  end-page: 265
  ident: bib36
  article-title: Selective ablation of human embryonic stem cells expressing a “suicide” gene
  publication-title: Stem Cells
– volume: 264
  start-page: 19039
  year: 1989
  end-page: 19044
  ident: bib33
  article-title: Herpes simplex virus type 1 and human DNA polymerase interactions with 2'-deoxyguanosine 5'-triphosphate analogues. Kinetics of incorporation into DNA and induction of inhibition
  publication-title: J. Biol. Chem.
– volume: 4
  start-page: 860
  year: 2015
  end-page: 872
  ident: bib38
  article-title: Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients
  publication-title: Stem Cell Reports
– volume: 109
  start-page: 3826
  year: 2012
  end-page: 3831
  ident: bib12
  article-title: Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 29
  start-page: 267
  year: 2011
  end-page: 272
  ident: bib14
  article-title: Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells
  publication-title: Nat. Biotechnol.
– volume: 46
  start-page: 5276
  year: 1986
  end-page: 5281
  ident: bib25
  article-title: Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy
  publication-title: Cancer Res.
– volume: 26
  start-page: 903
  year: 2008
  end-page: 911
  ident: bib18
  article-title: Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells
  publication-title: Stem Cells
– volume: 83
  start-page: 283
  year: 2009
  end-page: 294
  ident: bib3
  article-title: Insertional gene activation by lentiviral and gammaretroviral vectors
  publication-title: J. Virol.
– volume: 8
  start-page: 345
  year: 2003
  end-page: 352
  ident: bib5
  article-title: Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
  publication-title: Apoptosis
– volume: 448
  start-page: 811
  year: 2007
  end-page: 815
  ident: bib35
  article-title: Cdk1 is sufficient to drive the mammalian cell cycle
  publication-title: Nature
– volume: 12
  start-page: 611
  year: 2019
  end-page: 623
  ident: bib29
  article-title: A double fail-safe approach to prevent tumorigenesis and select pancreatic beta cells from human embryonic stem cells
  publication-title: Stem Cell Reports
– volume: 12
  start-page: 611
  year: 2019
  ident: 10.1016/j.isci.2019.11.038_bib29
  article-title: A double fail-safe approach to prevent tumorigenesis and select pancreatic beta cells from human embryonic stem cells
  publication-title: Stem Cell Reports
  doi: 10.1016/j.stemcr.2019.01.012
– volume: 34
  start-page: 2635
  year: 2016
  ident: 10.1016/j.isci.2019.11.038_bib10
  article-title: Anterior-posterior patterning of definitive endoderm generated from human embryonic stem cells depends on the differential signaling of retinoic acid, Wnt-, and BMP-signaling
  publication-title: Stem Cells
  doi: 10.1002/stem.2428
– volume: 3
  start-page: 1550
  year: 2008
  ident: 10.1016/j.isci.2019.11.038_bib11
  article-title: A protocol for removal of antibiotic resistance cassettes from human embryonic stem cells genetically modified by homologous recombination or transgenesis
  publication-title: Nat. Protoc.
  doi: 10.1038/nprot.2008.146
– volume: 4
  start-page: 1103
  year: 2015
  ident: 10.1016/j.isci.2019.11.038_bib49
  article-title: A CRISPR/Cas-Mediated selection-free knockin strategy in human embryonic stem cells
  publication-title: Stem Cell Reports
  doi: 10.1016/j.stemcr.2015.04.016
– volume: 264
  start-page: 19039
  year: 1989
  ident: 10.1016/j.isci.2019.11.038_bib33
  article-title: Herpes simplex virus type 1 and human DNA polymerase interactions with 2'-deoxyguanosine 5'-triphosphate analogues. Kinetics of incorporation into DNA and induction of inhibition
  publication-title: J. Biol. Chem.
  doi: 10.1016/S0021-9258(19)47263-3
– volume: 1
  start-page: 14053
  year: 2014
  ident: 10.1016/j.isci.2019.11.038_bib44
  article-title: Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies
  publication-title: Mol. Ther. Methods Clin. Dev.
  doi: 10.1038/mtm.2014.53
– volume: 569
  start-page: 368
  year: 2019
  ident: 10.1016/j.isci.2019.11.038_bib42
  article-title: Charting cellular identity during human in vitro beta-cell differentiation
  publication-title: Nature
  doi: 10.1038/s41586-019-1168-5
– volume: 7
  start-page: e40167
  year: 2018
  ident: 10.1016/j.isci.2019.11.038_bib20
  article-title: Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation
  publication-title: Elife
  doi: 10.7554/eLife.40167
– volume: 4
  start-page: 16849
  year: 2013
  ident: 10.1016/j.isci.2019.11.038_bib48
  article-title: Suicide gene therapy for cancer - current strategies
  publication-title: J. Genet. Syndr. Gene Ther.
– volume: 2
  start-page: 198
  year: 2009
  ident: 10.1016/j.isci.2019.11.038_bib15
  article-title: Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies
  publication-title: Stem Cell Res.
  doi: 10.1016/j.scr.2009.02.002
– volume: 563
  start-page: 701
  year: 2018
  ident: 10.1016/j.isci.2019.11.038_bib23
  article-title: Linking a cell-division gene and a suicide gene to define and improve cell therapy safety
  publication-title: Nature
  doi: 10.1038/s41586-018-0733-7
– volume: 23
  start-page: 1475
  year: 2015
  ident: 10.1016/j.isci.2019.11.038_bib45
  article-title: An inducible caspase-9 suicide gene to improve the safety of therapy using human induced pluripotent stem cells
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2015.100
– volume: 275
  start-page: 1129
  year: 1997
  ident: 10.1016/j.isci.2019.11.038_bib46
  article-title: Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked
  publication-title: Science
  doi: 10.1126/science.275.5303.1129
– volume: 23
  start-page: 105
  year: 2017
  ident: 10.1016/j.isci.2019.11.038_bib1
  article-title: Generation of an OCT4 reporter human induced pluripotent stem cell line using CRISPR/SpCas9
  publication-title: Stem Cell Res.
  doi: 10.1016/j.scr.2017.07.006
– volume: 276
  start-page: 1719
  year: 1997
  ident: 10.1016/j.isci.2019.11.038_bib4
  article-title: HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia
  publication-title: Science
  doi: 10.1126/science.276.5319.1719
– volume: 9
  start-page: e114275
  year: 2014
  ident: 10.1016/j.isci.2019.11.038_bib19
  article-title: TALEN/CRISPR-mediated eGFP knock-in add-on at the OCT4 locus does not impact differentiation of human embryonic stem cells towards endoderm
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0114275
– volume: 110
  start-page: 385
  year: 2002
  ident: 10.1016/j.isci.2019.11.038_bib43
  article-title: Directed differentiation of embryonic stem cells into motor neurons
  publication-title: Cell
  doi: 10.1016/S0092-8674(02)00835-8
– volume: 32
  start-page: 1121
  year: 2014
  ident: 10.1016/j.isci.2019.11.038_bib34
  article-title: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.3033
– volume: 46
  start-page: 5276
  year: 1986
  ident: 10.1016/j.isci.2019.11.038_bib25
  article-title: Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy
  publication-title: Cancer Res.
– volume: 154
  start-page: 1380
  year: 2013
  ident: 10.1016/j.isci.2019.11.038_bib32
  article-title: Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
  publication-title: Cell
  doi: 10.1016/j.cell.2013.08.021
– volume: 448
  start-page: 811
  year: 2007
  ident: 10.1016/j.isci.2019.11.038_bib35
  article-title: Cdk1 is sufficient to drive the mammalian cell cycle
  publication-title: Nature
  doi: 10.1038/nature06046
– volume: 6
  start-page: 217
  year: 2004
  ident: 10.1016/j.isci.2019.11.038_bib17
  article-title: Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics
  publication-title: Cloning Stem Cells
  doi: 10.1089/clo.2004.6.217
– volume: 83
  start-page: 283
  year: 2009
  ident: 10.1016/j.isci.2019.11.038_bib3
  article-title: Insertional gene activation by lentiviral and gammaretroviral vectors
  publication-title: J. Virol.
  doi: 10.1128/JVI.01865-08
– volume: 4
  start-page: 860
  year: 2015
  ident: 10.1016/j.isci.2019.11.038_bib38
  article-title: Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients
  publication-title: Stem Cell Reports
  doi: 10.1016/j.stemcr.2015.04.005
– volume: 282
  start-page: 1145
  year: 1998
  ident: 10.1016/j.isci.2019.11.038_bib41
  article-title: Embryonic stem cell lines derived from human blastocysts
  publication-title: Science
  doi: 10.1126/science.282.5391.1145
– volume: 95
  start-page: 10437
  year: 1998
  ident: 10.1016/j.isci.2019.11.038_bib9
  article-title: Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.95.18.10437
– volume: 27
  start-page: 851
  year: 2009
  ident: 10.1016/j.isci.2019.11.038_bib16
  article-title: Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.1562
– volume: 159
  start-page: 428
  year: 2014
  ident: 10.1016/j.isci.2019.11.038_bib28
  article-title: Generation of functional human pancreatic beta cells in vitro
  publication-title: Cell
  doi: 10.1016/j.cell.2014.09.040
– volume: 33
  start-page: 3195
  year: 2012
  ident: 10.1016/j.isci.2019.11.038_bib8
  article-title: Protecting against wayward human induced pluripotent stem cells with a suicide gene
  publication-title: Biomaterials
  doi: 10.1016/j.biomaterials.2012.01.023
– volume: 29
  start-page: 267
  year: 2011
  ident: 10.1016/j.isci.2019.11.038_bib14
  article-title: Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.1788
– volume: 8
  start-page: e81131
  year: 2013
  ident: 10.1016/j.isci.2019.11.038_bib27
  article-title: Targeting of herpes simplex virus 1 thymidine kinase gene sequences into the OCT4 locus of human induced pluripotent stem cells
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0081131
– volume: 71
  start-page: 429
  year: 2018
  ident: 10.1016/j.isci.2019.11.038_bib24
  article-title: Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic Left ventricular dysfunction
  publication-title: J. Am. Coll. Cardiol.
  doi: 10.1016/j.jacc.2017.11.047
– volume: 13
  start-page: 2329
  year: 2018
  ident: 10.1016/j.isci.2019.11.038_bib31
  article-title: Targeted elimination of tumorigenic human pluripotent stem cells using suicide-inducing virus-like particles
  publication-title: ACS Chem. Biol.
  doi: 10.1021/acschembio.8b00490
– volume: 21
  start-page: 257
  year: 2003
  ident: 10.1016/j.isci.2019.11.038_bib36
  article-title: Selective ablation of human embryonic stem cells expressing a “suicide” gene
  publication-title: Stem Cells
  doi: 10.1634/stemcells.21-3-257
– volume: 110
  start-page: E3281
  year: 2013
  ident: 10.1016/j.isci.2019.11.038_bib21
  article-title: Inhibition of pluripotent stem cell-derived teratoma formation by small molecules
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.1303669110
– volume: 282
  start-page: 33888
  year: 2007
  ident: 10.1016/j.isci.2019.11.038_bib6
  article-title: Caspase-9-induced mitochondrial disruption through cleavage of anti-apoptotic BCL-2 family members
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M702969200
– volume: 385
  start-page: 509
  year: 2015
  ident: 10.1016/j.isci.2019.11.038_bib37
  article-title: Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies
  publication-title: Lancet
  doi: 10.1016/S0140-6736(14)61376-3
– volume: 9
  start-page: 47
  year: 2008
  ident: 10.1016/j.isci.2019.11.038_bib47
  article-title: The BCL-2 protein family: opposing activities that mediate cell death
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/nrm2308
– volume: 278
  start-page: 1966
  year: 1997
  ident: 10.1016/j.isci.2019.11.038_bib7
  article-title: Conversion of Bcl-2 to a Bax-like death effector by caspases
  publication-title: Science
  doi: 10.1126/science.278.5345.1966
– volume: 9
  start-page: 34
  year: 2013
  ident: 10.1016/j.isci.2019.11.038_bib22
  article-title: Safeguarding clinical translation of pluripotent stem cells with suicide genes
  publication-title: Organogenesis
  doi: 10.4161/org.24317
– volume: 145
  start-page: 98
  year: 2016
  ident: 10.1016/j.isci.2019.11.038_bib40
  article-title: Human cardiomyocyte generation from pluripotent stem cells: a state-of-art
  publication-title: Life Sci.
  doi: 10.1016/j.lfs.2015.12.023
– volume: 8
  start-page: 345
  year: 2003
  ident: 10.1016/j.isci.2019.11.038_bib5
  article-title: Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
  publication-title: Apoptosis
  doi: 10.1023/A:1024116916932
– volume: 35
  start-page: 1773
  year: 2007
  ident: 10.1016/j.isci.2019.11.038_bib2
  article-title: Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkm059
– volume: 105
  start-page: 4247
  year: 2005
  ident: 10.1016/j.isci.2019.11.038_bib39
  article-title: An inducible caspase 9 safety switch for T-cell therapy
  publication-title: Blood
  doi: 10.1182/blood-2004-11-4564
– volume: 134
  start-page: 2521
  year: 2007
  ident: 10.1016/j.isci.2019.11.038_bib30
  article-title: Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm
  publication-title: Development
  doi: 10.1242/dev.003855
– volume: 26
  start-page: 903
  year: 2008
  ident: 10.1016/j.isci.2019.11.038_bib18
  article-title: Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells
  publication-title: Stem Cells
  doi: 10.1634/stemcells.2007-0951
– volume: 39
  start-page: 749
  year: 2003
  ident: 10.1016/j.isci.2019.11.038_bib13
  article-title: SOX2 functions to maintain neural progenitor identity
  publication-title: Neuron
  doi: 10.1016/S0896-6273(03)00497-5
– volume: 109
  start-page: 3826
  year: 2012
  ident: 10.1016/j.isci.2019.11.038_bib12
  article-title: Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.1115201109
– volume: 106
  start-page: 1601
  year: 2005
  ident: 10.1016/j.isci.2019.11.038_bib26
  article-title: Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation
  publication-title: Blood
  doi: 10.1182/blood-2005-03-0987
SSID ssj0002002496
Score 2.2074397
Snippet A major challenge in using human pluripotent stem cells (hPSCs) in therapy is the risk of teratoma formation due to contaminating undifferentiated stem cells....
SourceID doaj
pubmedcentral
proquest
pubmed
crossref
elsevier
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 409
SubjectTerms Cellular Therapy
Stem Cells Research
Techniques in Genetics
Title Using Gene Editing to Establish a Safeguard System for Pluripotent Stem-Cell-Based Therapies
URI https://dx.doi.org/10.1016/j.isci.2019.11.038
https://www.ncbi.nlm.nih.gov/pubmed/31821946
https://www.proquest.com/docview/2324916683
https://pubmed.ncbi.nlm.nih.gov/PMC6909005
https://doaj.org/article/c1325e2cafec4dfc9b702089adcfe458
Volume 22
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LS8QwEA7iyYsovuqLCN4k2m3TNjm6siKCIqjgQQh56srSFe3-f2fS7rKroBevbbftTKaZL5tvviHkOAu5yGzVYzD5p4x7aZhJq4p5rR2kD69lbMlyc1tePfLrp-JprtUXcsJaeeDWcWcWlkuFz6wO3nIXrDQV9pWU2tngeRHLfCHnzS2m3uL2Gkrhxc5yBXKCIDS7ipmW3IUVr8jrkqco4YnFKXNZKYr3LySnn-DzO4dyLildrpHVDk3S89aKdbLk6w3yHGkAFAWl6cANkddMmzEdAA6MfzlRTe_BzhcMDtoqllOArvRuNIEZZAwguqH3cJBd-NGI9SHNOfoQy7RgVb1JHi8HDxdXrGuiwGwhqoYhxJHOppXlhYGh6IkgBTc2yyR3WuhK-DyVAF6NyYMTAhBLmfcga5fgZB9cvkWW63Htdwj1ZZCl5Kn1TnONWmjOWBFcyKXD3cGE9KZOVLZTGMdGFyM1pZK9KXS8QsfD0kOB4xNyMvvNe6uv8evVfRyb2ZWojR0PQMSoLmLUXxGTkGI6sqqDGS18gFsNf3340TQMFHyDuLGiaz-efCpEpQCzS5EnZLsNi9krwpwJSYGXCakWAmbBhsUz9fA16nyXMpUwSe7-h9F7ZAVNQSJOlu6T5eZj4g8ATjXmMH45X-iZHjw
linkProvider Directory of Open Access Journals
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Using+Gene+Editing+to+Establish+a+Safeguard+System+for+Pluripotent+Stem-Cell-Based+Therapies&rft.jtitle=iScience&rft.au=Wu%2C+Youjun&rft.au=Chang%2C+Tammy&rft.au=Long%2C+Yan&rft.au=Huang%2C+He&rft.date=2019-12-20&rft.pub=Elsevier+Inc&rft.issn=2589-0042&rft.eissn=2589-0042&rft.volume=22&rft.spage=409&rft.epage=422&rft_id=info:doi/10.1016%2Fj.isci.2019.11.038&rft.externalDocID=S2589004219304894
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2589-0042&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2589-0042&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2589-0042&client=summon