{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:27:25Z","timestamp":1791217645298,"version":"4.1.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T00:00:00Z","timestamp":1381449600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0077673","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T23:13:18Z","timestamp":1381533198000},"page":"e77673","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":215,"title":["Generation of 3D Skin Equivalents Fully Reconstituted from Human Induced Pluripotent Stem Cells (iPSCs)"],"prefix":"10.1371","volume":"8","author":[{"given":"Munenari","family":"Itoh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Umegaki-Arao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyou","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire A.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Christiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,10,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"K Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.gde.2012.05.005","article-title":"New lessons learned from disease modeling with induced pluripotent stem cells","volume":"22","author":"TT Onder","year":"2012","journal-title":"Curr Opin Genet Dev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI115938","article-title":"Molecular Genetics of the Cutaneous Basement Membrane Zone","volume":"90","author":"J Uitto","year":"1992","journal-title":"J Clin Invest"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jaad.2008.09.035","article-title":"Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006","volume":"60","author":"J-D Fine","year":"2009","journal-title":"J Am Acad Dermat"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/jid.2011.389","article-title":"Novel Molecular Therapies for Heritable Skin Disorders","volume":"132","author":"J Uitto","year":"2011","journal-title":"J Invest Dermatol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1046\/j.1523-1747.2003.12571.x","article-title":"Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can produce type VII collagen at the basement membrane zone","volume":"121","author":"DT Woodley","year":"2003","journal-title":"J Invest Dermatol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1172\/JCI200317193","article-title":"Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue","volume":"111","author":"S Ortiz-Urda","year":"2003","journal-title":"J Clin Invest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/sj.mt.6300041","article-title":"Intravenously injected human fibroblasts home to skin wounds, deliver type VII collagen, and promote wound healing","volume":"15","author":"DT Woodley","year":"2007","journal-title":"Molecular Therapy"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1172\/JCI34292","article-title":"A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy","volume":"118","author":"A Fritsch","year":"2008","journal-title":"J Clin Invest"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1038\/jid.2008.78","article-title":"Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa","volume":"128","author":"T Wong","year":"2008","journal-title":"J Invest Dermatol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1073\/pnas.1100332108","article-title":"Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells","volume":"108","author":"M Itoh","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1101\/gad.1303605","article-title":"Embryonic stem cell differentiation: emergence of a new era in biology and medicine","volume":"19","author":"G Keller","year":"2005","journal-title":"Genes Dev"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1753-4887.1992.tb01271.x","article-title":"The role of ascorbic acid in mesenchymal differentiation","volume":"50","author":"RT Franceschi","year":"1992","journal-title":"Nutr Rev"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1001\/archderm.1987.01660360122023","article-title":"Induction of collagen synthesis by ascorbic acid: a possible mechanism","volume":"123","author":"S Pinnell","year":"1987","journal-title":"Arch Dermatol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1161\/01.CIR.0000064899.53876.A3","article-title":"Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes","volume":"107","author":"T Takahashi","year":"2003","journal-title":"Circulation"},{"key":"ref16","first-page":"129","article-title":"MESODERMAL DIFFERENTIATION. Human cell culture 6","author":"N Sharon","year":"2007"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1471-213X-10-69","article-title":"Tgfbeta2 and 3 are coexpressed with their extracellular regulator Ltbp1 in the early limb bud and modulate mesodermal outgrowth and BMP signaling in chicken embryos","volume":"10","author":"CI Lorda-Diez","year":"2010","journal-title":"BMC Dev Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbrc.2005.04.098","article-title":"Transforming growth factor-beta2 enhances differentiation of cardiac myocytes from embryonic stem cells","volume":"332","author":"DK Singla","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2008.323","article-title":"Roles of TGF-beta family signaling in stem cell renewal and differentiation","volume":"19","author":"T Watabe","year":"2009","journal-title":"Cell Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1172\/JCI117154","article-title":"Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta","volume":"93","author":"L Rudnicka","year":"1994","journal-title":"J Clin Invest"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0021-9258(17)42303-9","article-title":"Differential cytokine regulation of type I and type VII collagen gene expression in cultured human dermal fibroblasts","volume":"269","author":"A Mauviel","year":"1994","journal-title":"J Biol Chemistry"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1158\/1541-7786.MCR-07-0294","article-title":"Transforming growth factor-beta1, transforming growth factor-beta2, and transforming growth factor-beta3 enhance ovarian cancer metastatic potential by inducing a Smad3-dependent epithelial-to-mesenchymal transition","volume":"6","author":"T-V Do","year":"2008","journal-title":"Mol Cancer Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/dvdy.21854","article-title":"Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development","volume":"238","author":"M Azhar","year":"2009","journal-title":"Dev Dynam"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s11626-010-9367-2","article-title":"Differentiation of embryonic stem cells into fibroblast-like cells in three-dimensional type I collagen gel cultures","volume":"47","author":"S Togo","year":"2011","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/humrep\/dep003","article-title":"Novel autogenic feeders derived from human embryonic stem cells (hESCs) support an undifferentiated status of hESCs in xeno-free culture conditions","volume":"24","author":"H-F Chen","year":"2009","journal-title":"Human Reproduction"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1634\/stemcells.22-6-972","article-title":"Immortalized fibroblast-like cells derived from human embryonic stem cells support undifferentiated cell growth","volume":"22","author":"C Xu","year":"2004","journal-title":"Stem Cells"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0945-053X(03)00006-4","article-title":"Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis","volume":"22","author":"J Myllyharju","year":"2003","journal-title":"Matrix Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.stem.2009.05.023","article-title":"Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells","volume":"5","author":"J Zou","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nature10424","article-title":"Targeted gene correction of \u03b11-antitrypsin deficiency in induced pluripotent stem cells","volume":"478","author":"K Yusa","year":"2011","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1182\/blood-2011-02-335554","article-title":"Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease","volume":"118","author":"J Zou","year":"2011","journal-title":"Blood"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"6537","DOI":"10.1073\/pnas.1103388108","article-title":"Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy","volume":"108","author":"SE Howden","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nbt.1927","article-title":"Genetic engineering of human pluripotent cells using TALE nucleases","volume":"29","author":"D Hockemeyer","year":"2011","journal-title":"Nat Biotechnol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1242\/jcs.042895","article-title":"Increased invasive behaviour in cutaneous squamous cell carcinoma with loss of basement-membrane type VII collagen","volume":"122","author":"VL Martins","year":"2009","journal-title":"J Cell Sci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.1038\/onc.2011.180","article-title":"Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma","volume":"30","author":"SA Watt","year":"2011","journal-title":"Oncogene"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1158\/0008-5472.CAN-11-2996","article-title":"Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa","volume":"72","author":"Y-Z Ng","year":"2012","journal-title":"Cancer Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e17128","DOI":"10.1371\/journal.pone.0017128","article-title":"Epigenetic and Phenotypic Profile of Fibroblasts Derived from Induced Pluripotent Stem Cells","volume":"6","author":"KJ Hewitt","year":"2011","journal-title":"PLOS ONE"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1089\/ten.tea.2009.0060","article-title":"Three-dimensional epithelial tissues generated from human embryonic stem cells","volume":"15","author":"KJ Hewitt","year":"2009","journal-title":"Tissue Eng A"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s11626-011-9478-4","article-title":"iPSC-derived fibroblasts demonstrate augmented production and assembly of extracellular matrix proteins","volume":"48","author":"Y Shamis","year":"2012","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0896-6273(00)00083-0","article-title":"Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity","volume":"28","author":"H Kawasaki","year":"2000","journal-title":"Neuron"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"11307","DOI":"10.1073\/pnas.97.21.11307","article-title":"Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells","volume":"97","author":"M Schuldiner","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/(SICI)1096-8628(19990806)85:4<361::AID-AJMG11>3.0.CO;2-E","article-title":"Revertant mosaicism in human genetic disorders","volume":"85","author":"MF Jonkman","year":"1999","journal-title":"Am J Med Genet"},{"key":"ref42","first-page":"1","article-title":"Three-Dimensional Tissue Models of Normal and Diseased Skin","volume":"19","author":"MW Carlson","year":"2008","journal-title":"Current Protoc Cell Biol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0077673","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T19:07:08Z","timestamp":1646766428000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0077673"}},"subtitle":[],"editor":[{"given":"Richard\u00a0L.","family":"Eckert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,10,11]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2013,10,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0077673","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718151082.793493602","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,11]]}}}