Function and Immunogenicity of Gene-corrected iPSC-derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Hirofumi Okada, Chiaki Nakanishi, Shohei Yoshida, Masaya Shimojima, Junichiro Yokawa, Masayuki Mori, Hayato Tada, Tsuyoshi Yoshimuta, Kenshi Hayashi, Tomoyoshi Yamano, Rikinari Hanayama, Masakazu Yamagishi, Masa-aki Kawashiri

ABSTRACT

Gene correction of induced pluripotent stem cells (iPSCs) has therapeutic potential for treating homozygous familial hypercholesterolemia (HoFH) associated with low-density lipoprotein (LDL) receptor (LDLR) dysfunction. However, few data exist regarding the functional recovery and immunogenicity of LDLR gene-corrected iPSC-derived hepatocyte-like cells (HLCs) obtained from an HoFH patient. Therefore, we generated iPSC-derived HLCs from an HoFH patient harbouring a point mutation (NM_000527.4:c.901 G > T) in exon 6 of LDLR, and examined their function and immunogenicity. From the patient's iPSCs, one homozygous gene-corrected HoFH-iPSC clone and two heterozygous clones were generated using the CRISPR/Cas9 method. Both types of iPSC-derived HLCs showed recovery of the function of LDL uptake in immunofluorescence staining analysis. Furthermore, these gene-corrected iPSC-derived HLCs showed little immunogenicity against the patient's peripheral blood mononuclear cells in a cell-mediated cytotoxicity assay. These results demonstrate that LDL uptake of iPSC-derived HLCs from HoFH can be restored by gene correction without the appearance of further immunogenicity, suggesting that gene-corrected iPSC-derived HLCs are applicable to the treatment of HoFH. More... »

PAGES

4695

Journal

TITLE

Scientific Reports

ISSUE

1

VOLUME

9

From Grant

  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-41056-w

    DOI

    http://dx.doi.org/10.1038/s41598-019-41056-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112857461

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30886174


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1004", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical Biotechnology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/10", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Technology", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Okada", 
            "givenName": "Hirofumi", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nakanishi", 
            "givenName": "Chiaki", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yoshida", 
            "givenName": "Shohei", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Shimojima", 
            "givenName": "Masaya", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yokawa", 
            "givenName": "Junichiro", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mori", 
            "givenName": "Masayuki", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tada", 
            "givenName": "Hayato", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yoshimuta", 
            "givenName": "Tsuyoshi", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hayashi", 
            "givenName": "Kenshi", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Immunology, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8640, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yamano", 
            "givenName": "Tomoyoshi", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Immunology, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8640, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hanayama", 
            "givenName": "Rikinari", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Osaka University of Human Sciences", 
              "id": "https://www.grid.ac/institutes/grid.444772.6", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan", 
                "Department of Human Sciences, Osaka University of Human Sciences, 1-12-13 Shoya, 566-8501, Settsu, Osaka, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yamagishi", 
            "givenName": "Masakazu", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Kanazawa University", 
              "id": "https://www.grid.ac/institutes/grid.9707.9", 
              "name": [
                "Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kawashiri", 
            "givenName": "Masa-aki", 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nm1195-1148", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001210751", 
              "https://doi.org/10.1038/nm1195-1148"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm1195-1148", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001210751", 
              "https://doi.org/10.1038/nm1195-1148"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0378-1119(96)00540-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003005633"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1146/annurev.ge.24.120190.001025", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003391543"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stemcr.2014.10.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005738478"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stemcr.2014.10.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005738478"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stemcr.2014.10.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005738478"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2623", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009511624", 
              "https://doi.org/10.1038/nbt.2623"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci110184", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013885564"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1161/01.cir.79.2.225", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014162839"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2006.07.024", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014573758"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/humrep/dep244", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016756683"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/humrep/dep244", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016756683"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m116.719237", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017474252"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1194/jlr.m300482-jlr200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018079779"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/hep.25871", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018274580"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0140-6736(14)61374-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018757693"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.5551/jat.14.94", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019179811"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1231143", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019873131"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/hep.23354", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020076080"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.exphem.2015.06.002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021902712"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1232033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022072971"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.transci.2004.01.006", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023240623"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2012.153", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023392144", 
              "https://doi.org/10.1038/nprot.2012.153"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci43122", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024382505"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci43122", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024382505"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1006/mthe.2000.0122", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024668037"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejmoa061189", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024908095"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0022-1759(01)00507-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026632326"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2012.015", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026868186", 
              "https://doi.org/10.1038/nprot.2012.015"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1586/erv.10.49", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029209532"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cr.2009.107", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031896668", 
              "https://doi.org/10.1038/cr.2009.107"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00380-013-0391-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039195009", 
              "https://doi.org/10.1007/s00380-013-0391-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.atherosclerosis.2010.11.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041281330"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1225829", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041850060"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12033-012-9635-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044681532", 
              "https://doi.org/10.1007/s12033-012-9635-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.amjcard.2011.09.019", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049806168"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/00000658-199602000-00002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1060134195"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci18925", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063416376"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep44312", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084132205", 
              "https://doi.org/10.1038/srep44312"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/hep4.1110", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092239680"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.yjmcc.2017.11.019", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092999647"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-12", 
        "datePublishedReg": "2019-12-01", 
        "description": "Gene correction of induced pluripotent stem cells (iPSCs) has therapeutic potential for treating homozygous familial hypercholesterolemia (HoFH) associated with low-density lipoprotein (LDL) receptor (LDLR) dysfunction. However, few data exist regarding the functional recovery and immunogenicity of LDLR gene-corrected iPSC-derived hepatocyte-like cells (HLCs) obtained from an HoFH patient. Therefore, we generated iPSC-derived HLCs from an HoFH patient harbouring a point mutation (NM_000527.4:c.901\u2009G\u2009>\u2009T) in exon 6 of LDLR, and examined their function and immunogenicity. From the patient's iPSCs, one homozygous gene-corrected HoFH-iPSC clone and two heterozygous clones were generated using the CRISPR/Cas9 method. Both types of iPSC-derived HLCs showed recovery of the function of LDL uptake in immunofluorescence staining analysis. Furthermore, these gene-corrected iPSC-derived HLCs showed little immunogenicity against the patient's peripheral blood mononuclear cells in a cell-mediated cytotoxicity assay. These results demonstrate that LDL uptake of iPSC-derived HLCs from HoFH can be restored by gene correction without the appearance of further immunogenicity, suggesting that gene-corrected iPSC-derived HLCs are applicable to the treatment of HoFH.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/s41598-019-41056-w", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.5884817", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "9"
          }
        ], 
        "name": "Function and Immunogenicity of Gene-corrected iPSC-derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia", 
        "pagination": "4695", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "d3ccef4959959e02f4ffba7c302f52306c29383304710436e605d0e3c604dfed"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30886174"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101563288"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-019-41056-w"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1112857461"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-019-41056-w", 
          "https://app.dimensions.ai/details/publication/pub.1112857461"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T13:18", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000368_0000000368/records_78938_00000001.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/s41598-019-41056-w"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41056-w'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41056-w'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41056-w'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41056-w'


     

    This table displays all metadata directly associated to this object as RDF triples.

    265 TRIPLES      21 PREDICATES      66 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-019-41056-w schema:about anzsrc-for:10
    2 anzsrc-for:1004
    3 schema:author N9aaf9995fb7e4a3a88c743e3fe8a4ede
    4 schema:citation sg:pub.10.1007/s00380-013-0391-5
    5 sg:pub.10.1007/s12033-012-9635-3
    6 sg:pub.10.1038/cr.2009.107
    7 sg:pub.10.1038/nbt.2623
    8 sg:pub.10.1038/nm1195-1148
    9 sg:pub.10.1038/nprot.2012.015
    10 sg:pub.10.1038/nprot.2012.153
    11 sg:pub.10.1038/srep44312
    12 https://doi.org/10.1002/hep.23354
    13 https://doi.org/10.1002/hep.25871
    14 https://doi.org/10.1002/hep4.1110
    15 https://doi.org/10.1006/mthe.2000.0122
    16 https://doi.org/10.1016/j.amjcard.2011.09.019
    17 https://doi.org/10.1016/j.atherosclerosis.2010.11.005
    18 https://doi.org/10.1016/j.cell.2006.07.024
    19 https://doi.org/10.1016/j.exphem.2015.06.002
    20 https://doi.org/10.1016/j.stemcr.2014.10.013
    21 https://doi.org/10.1016/j.transci.2004.01.006
    22 https://doi.org/10.1016/j.yjmcc.2017.11.019
    23 https://doi.org/10.1016/s0022-1759(01)00507-5
    24 https://doi.org/10.1016/s0140-6736(14)61374-x
    25 https://doi.org/10.1016/s0378-1119(96)00540-9
    26 https://doi.org/10.1056/nejmoa061189
    27 https://doi.org/10.1074/jbc.m116.719237
    28 https://doi.org/10.1093/humrep/dep244
    29 https://doi.org/10.1097/00000658-199602000-00002
    30 https://doi.org/10.1126/science.1225829
    31 https://doi.org/10.1126/science.1231143
    32 https://doi.org/10.1126/science.1232033
    33 https://doi.org/10.1146/annurev.ge.24.120190.001025
    34 https://doi.org/10.1161/01.cir.79.2.225
    35 https://doi.org/10.1172/jci110184
    36 https://doi.org/10.1172/jci18925
    37 https://doi.org/10.1172/jci43122
    38 https://doi.org/10.1194/jlr.m300482-jlr200
    39 https://doi.org/10.1586/erv.10.49
    40 https://doi.org/10.5551/jat.14.94
    41 schema:datePublished 2019-12
    42 schema:datePublishedReg 2019-12-01
    43 schema:description Gene correction of induced pluripotent stem cells (iPSCs) has therapeutic potential for treating homozygous familial hypercholesterolemia (HoFH) associated with low-density lipoprotein (LDL) receptor (LDLR) dysfunction. However, few data exist regarding the functional recovery and immunogenicity of LDLR gene-corrected iPSC-derived hepatocyte-like cells (HLCs) obtained from an HoFH patient. Therefore, we generated iPSC-derived HLCs from an HoFH patient harbouring a point mutation (NM_000527.4:c.901 G > T) in exon 6 of LDLR, and examined their function and immunogenicity. From the patient's iPSCs, one homozygous gene-corrected HoFH-iPSC clone and two heterozygous clones were generated using the CRISPR/Cas9 method. Both types of iPSC-derived HLCs showed recovery of the function of LDL uptake in immunofluorescence staining analysis. Furthermore, these gene-corrected iPSC-derived HLCs showed little immunogenicity against the patient's peripheral blood mononuclear cells in a cell-mediated cytotoxicity assay. These results demonstrate that LDL uptake of iPSC-derived HLCs from HoFH can be restored by gene correction without the appearance of further immunogenicity, suggesting that gene-corrected iPSC-derived HLCs are applicable to the treatment of HoFH.
    44 schema:genre research_article
    45 schema:inLanguage en
    46 schema:isAccessibleForFree true
    47 schema:isPartOf Nd43aab9b416c48fc980ee9eefcc04635
    48 Ne094d90369284db4a898b561815b16a7
    49 sg:journal.1045337
    50 schema:name Function and Immunogenicity of Gene-corrected iPSC-derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia
    51 schema:pagination 4695
    52 schema:productId N445383bdec6d47f5a7d2514205cd0c42
    53 N4775f3786b9c4d818e0a45eadeb18c99
    54 Nad5aab0918a84686badc6c44c325bc2a
    55 Nd5990741b0284438ab8574ae6b3acda0
    56 Nd9dd18ea8c2f41cbadc332342490e031
    57 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112857461
    58 https://doi.org/10.1038/s41598-019-41056-w
    59 schema:sdDatePublished 2019-04-11T13:18
    60 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    61 schema:sdPublisher Nf78ac198600b40f28cb40ae9072979bd
    62 schema:url https://www.nature.com/articles/s41598-019-41056-w
    63 sgo:license sg:explorer/license/
    64 sgo:sdDataset articles
    65 rdf:type schema:ScholarlyArticle
    66 N0c27c8962a504eb195b66232920b8b89 rdf:first N8a75a6c8c37d4cdeae37572be54118a3
    67 rdf:rest rdf:nil
    68 N37c1cfc2f287492e8907b142db338719 schema:affiliation https://www.grid.ac/institutes/grid.444772.6
    69 schema:familyName Yamagishi
    70 schema:givenName Masakazu
    71 rdf:type schema:Person
    72 N445383bdec6d47f5a7d2514205cd0c42 schema:name pubmed_id
    73 schema:value 30886174
    74 rdf:type schema:PropertyValue
    75 N44d83e89bb2a4a7088e9b704377b118f rdf:first N4769fd7e0eb44ff39bdd330cf974f034
    76 rdf:rest N910cb9dd04f2499588740a717b50ae58
    77 N4769fd7e0eb44ff39bdd330cf974f034 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    78 schema:familyName Hanayama
    79 schema:givenName Rikinari
    80 rdf:type schema:Person
    81 N4775f3786b9c4d818e0a45eadeb18c99 schema:name readcube_id
    82 schema:value d3ccef4959959e02f4ffba7c302f52306c29383304710436e605d0e3c604dfed
    83 rdf:type schema:PropertyValue
    84 N504538302c54415a946a343ccfb265f9 rdf:first Nb1df881d771d4239972caf8cc917b981
    85 rdf:rest N8da764f508c941ac93f6ebb704b16473
    86 N5b06e400cfe348758e7825d83aa9eed1 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    87 schema:familyName Tada
    88 schema:givenName Hayato
    89 rdf:type schema:Person
    90 N608a519c2ef4442480316726284cca09 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    91 schema:familyName Shimojima
    92 schema:givenName Masaya
    93 rdf:type schema:Person
    94 N7a8c411f65cf49019fe0286f8b68acd2 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    95 schema:familyName Okada
    96 schema:givenName Hirofumi
    97 rdf:type schema:Person
    98 N8015948ab8fa4b11830e40cf63ecfc49 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    99 schema:familyName Nakanishi
    100 schema:givenName Chiaki
    101 rdf:type schema:Person
    102 N8a75a6c8c37d4cdeae37572be54118a3 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    103 schema:familyName Kawashiri
    104 schema:givenName Masa-aki
    105 rdf:type schema:Person
    106 N8da764f508c941ac93f6ebb704b16473 rdf:first N5b06e400cfe348758e7825d83aa9eed1
    107 rdf:rest Ncf4a51b4cfd94cbb80d96c5d95556528
    108 N910cb9dd04f2499588740a717b50ae58 rdf:first N37c1cfc2f287492e8907b142db338719
    109 rdf:rest N0c27c8962a504eb195b66232920b8b89
    110 N9aaf9995fb7e4a3a88c743e3fe8a4ede rdf:first N7a8c411f65cf49019fe0286f8b68acd2
    111 rdf:rest Ndb15f914b5724b8ab1842ea85b0a8529
    112 N9bed64352e814e7793672535bde69a8b schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    113 schema:familyName Yamano
    114 schema:givenName Tomoyoshi
    115 rdf:type schema:Person
    116 Nad272bdd85fa46b6bdcae74c171ae791 rdf:first Nd18d3d116b1a45a3a50d79c54ab6074c
    117 rdf:rest N504538302c54415a946a343ccfb265f9
    118 Nad2af09df32e4a82a4a9541f2def2c28 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    119 schema:familyName Yoshida
    120 schema:givenName Shohei
    121 rdf:type schema:Person
    122 Nad5aab0918a84686badc6c44c325bc2a schema:name nlm_unique_id
    123 schema:value 101563288
    124 rdf:type schema:PropertyValue
    125 Nb1df881d771d4239972caf8cc917b981 schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    126 schema:familyName Mori
    127 schema:givenName Masayuki
    128 rdf:type schema:Person
    129 Nb6b0b16e01b84821a7994834f288b1d5 rdf:first Nad2af09df32e4a82a4a9541f2def2c28
    130 rdf:rest Nfe8546a96b2e4761890f561803568b11
    131 Nb7b43fadea124df8ba280b180f1e905e rdf:first N9bed64352e814e7793672535bde69a8b
    132 rdf:rest N44d83e89bb2a4a7088e9b704377b118f
    133 Ncf4a51b4cfd94cbb80d96c5d95556528 rdf:first Nfe8ffc61b69446188d9b20b8dd11bb8e
    134 rdf:rest Necc432917af34640a82bdbc687e9caa7
    135 Nd18d3d116b1a45a3a50d79c54ab6074c schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    136 schema:familyName Yokawa
    137 schema:givenName Junichiro
    138 rdf:type schema:Person
    139 Nd43aab9b416c48fc980ee9eefcc04635 schema:issueNumber 1
    140 rdf:type schema:PublicationIssue
    141 Nd5990741b0284438ab8574ae6b3acda0 schema:name doi
    142 schema:value 10.1038/s41598-019-41056-w
    143 rdf:type schema:PropertyValue
    144 Nd9dd18ea8c2f41cbadc332342490e031 schema:name dimensions_id
    145 schema:value pub.1112857461
    146 rdf:type schema:PropertyValue
    147 Ndb15f914b5724b8ab1842ea85b0a8529 rdf:first N8015948ab8fa4b11830e40cf63ecfc49
    148 rdf:rest Nb6b0b16e01b84821a7994834f288b1d5
    149 Ne0376a2d13c5433c9c58c5cb02080ffc schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    150 schema:familyName Hayashi
    151 schema:givenName Kenshi
    152 rdf:type schema:Person
    153 Ne094d90369284db4a898b561815b16a7 schema:volumeNumber 9
    154 rdf:type schema:PublicationVolume
    155 Necc432917af34640a82bdbc687e9caa7 rdf:first Ne0376a2d13c5433c9c58c5cb02080ffc
    156 rdf:rest Nb7b43fadea124df8ba280b180f1e905e
    157 Nf78ac198600b40f28cb40ae9072979bd schema:name Springer Nature - SN SciGraph project
    158 rdf:type schema:Organization
    159 Nfe8546a96b2e4761890f561803568b11 rdf:first N608a519c2ef4442480316726284cca09
    160 rdf:rest Nad272bdd85fa46b6bdcae74c171ae791
    161 Nfe8ffc61b69446188d9b20b8dd11bb8e schema:affiliation https://www.grid.ac/institutes/grid.9707.9
    162 schema:familyName Yoshimuta
    163 schema:givenName Tsuyoshi
    164 rdf:type schema:Person
    165 anzsrc-for:10 schema:inDefinedTermSet anzsrc-for:
    166 schema:name Technology
    167 rdf:type schema:DefinedTerm
    168 anzsrc-for:1004 schema:inDefinedTermSet anzsrc-for:
    169 schema:name Medical Biotechnology
    170 rdf:type schema:DefinedTerm
    171 sg:grant.5884817 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-41056-w
    172 rdf:type schema:MonetaryGrant
    173 sg:journal.1045337 schema:issn 2045-2322
    174 schema:name Scientific Reports
    175 rdf:type schema:Periodical
    176 sg:pub.10.1007/s00380-013-0391-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039195009
    177 https://doi.org/10.1007/s00380-013-0391-5
    178 rdf:type schema:CreativeWork
    179 sg:pub.10.1007/s12033-012-9635-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044681532
    180 https://doi.org/10.1007/s12033-012-9635-3
    181 rdf:type schema:CreativeWork
    182 sg:pub.10.1038/cr.2009.107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031896668
    183 https://doi.org/10.1038/cr.2009.107
    184 rdf:type schema:CreativeWork
    185 sg:pub.10.1038/nbt.2623 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009511624
    186 https://doi.org/10.1038/nbt.2623
    187 rdf:type schema:CreativeWork
    188 sg:pub.10.1038/nm1195-1148 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001210751
    189 https://doi.org/10.1038/nm1195-1148
    190 rdf:type schema:CreativeWork
    191 sg:pub.10.1038/nprot.2012.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026868186
    192 https://doi.org/10.1038/nprot.2012.015
    193 rdf:type schema:CreativeWork
    194 sg:pub.10.1038/nprot.2012.153 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023392144
    195 https://doi.org/10.1038/nprot.2012.153
    196 rdf:type schema:CreativeWork
    197 sg:pub.10.1038/srep44312 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084132205
    198 https://doi.org/10.1038/srep44312
    199 rdf:type schema:CreativeWork
    200 https://doi.org/10.1002/hep.23354 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020076080
    201 rdf:type schema:CreativeWork
    202 https://doi.org/10.1002/hep.25871 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018274580
    203 rdf:type schema:CreativeWork
    204 https://doi.org/10.1002/hep4.1110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092239680
    205 rdf:type schema:CreativeWork
    206 https://doi.org/10.1006/mthe.2000.0122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024668037
    207 rdf:type schema:CreativeWork
    208 https://doi.org/10.1016/j.amjcard.2011.09.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049806168
    209 rdf:type schema:CreativeWork
    210 https://doi.org/10.1016/j.atherosclerosis.2010.11.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041281330
    211 rdf:type schema:CreativeWork
    212 https://doi.org/10.1016/j.cell.2006.07.024 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014573758
    213 rdf:type schema:CreativeWork
    214 https://doi.org/10.1016/j.exphem.2015.06.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021902712
    215 rdf:type schema:CreativeWork
    216 https://doi.org/10.1016/j.stemcr.2014.10.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005738478
    217 rdf:type schema:CreativeWork
    218 https://doi.org/10.1016/j.transci.2004.01.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023240623
    219 rdf:type schema:CreativeWork
    220 https://doi.org/10.1016/j.yjmcc.2017.11.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092999647
    221 rdf:type schema:CreativeWork
    222 https://doi.org/10.1016/s0022-1759(01)00507-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026632326
    223 rdf:type schema:CreativeWork
    224 https://doi.org/10.1016/s0140-6736(14)61374-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1018757693
    225 rdf:type schema:CreativeWork
    226 https://doi.org/10.1016/s0378-1119(96)00540-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003005633
    227 rdf:type schema:CreativeWork
    228 https://doi.org/10.1056/nejmoa061189 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024908095
    229 rdf:type schema:CreativeWork
    230 https://doi.org/10.1074/jbc.m116.719237 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017474252
    231 rdf:type schema:CreativeWork
    232 https://doi.org/10.1093/humrep/dep244 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016756683
    233 rdf:type schema:CreativeWork
    234 https://doi.org/10.1097/00000658-199602000-00002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060134195
    235 rdf:type schema:CreativeWork
    236 https://doi.org/10.1126/science.1225829 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041850060
    237 rdf:type schema:CreativeWork
    238 https://doi.org/10.1126/science.1231143 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019873131
    239 rdf:type schema:CreativeWork
    240 https://doi.org/10.1126/science.1232033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022072971
    241 rdf:type schema:CreativeWork
    242 https://doi.org/10.1146/annurev.ge.24.120190.001025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003391543
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1161/01.cir.79.2.225 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014162839
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.1172/jci110184 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013885564
    247 rdf:type schema:CreativeWork
    248 https://doi.org/10.1172/jci18925 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063416376
    249 rdf:type schema:CreativeWork
    250 https://doi.org/10.1172/jci43122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024382505
    251 rdf:type schema:CreativeWork
    252 https://doi.org/10.1194/jlr.m300482-jlr200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018079779
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1586/erv.10.49 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029209532
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.5551/jat.14.94 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019179811
    257 rdf:type schema:CreativeWork
    258 https://www.grid.ac/institutes/grid.444772.6 schema:alternateName Osaka University of Human Sciences
    259 schema:name Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan
    260 Department of Human Sciences, Osaka University of Human Sciences, 1-12-13 Shoya, 566-8501, Settsu, Osaka, Japan
    261 rdf:type schema:Organization
    262 https://www.grid.ac/institutes/grid.9707.9 schema:alternateName Kanazawa University
    263 schema:name Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8641, Kanazawa, Ishikawa, Japan
    264 Department of Immunology, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, 920-8640, Kanazawa, Ishikawa, Japan
    265 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...