{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:51:45Z","timestamp":1775857905588,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S002553\/1"],"award-info":[{"award-number":["MR\/S002553\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["602300"],"award-info":[{"award-number":["602300"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20414"],"award-info":[{"award-number":["20414"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Human\u2010induced pluripotent stem cells (hiPSCs) are reprogrammed somatic cells and are an excellent cell source for tissue engineering applications, disease modeling, and for understanding human development. HiPSC lines have now been generated from a diverse range of somatic cell types and have been reported to retain an epigenetic memory of their somatic origin. To date, the reprogramming of a true ligament has not been reported. The aim of this study is to generate iPSCs from human anterior cruciate ligament (ACL) cells. ACL cells from three above\u2010knee amputation donors, with donor matched dermal fibroblasts (DFs) were tested for reprogramming using an existing DF reprogramming protocol. ACL cells were, however, more sensitive than donor matched DF to transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2); displaying marked contraction, increased proliferation and increased <jats:italic>TNC<\/jats:italic> and <jats:italic>COMP<\/jats:italic> expression in vitro, which hindered reprogramming to iPSCs. Modification of the protocol by scoring the cell monolayer or by removal of TGF\u2010\u03b2 during ACL reprogramming resulted in emerging colonies being easier to identify and extract, increasing reprogramming efficiency. Following 30 passages in culture, the generated ACL derived iPSCs displayed pluripotency markers, normal karyotype and can successfully differentiate to cells of the three embryonic germ layers. This study illustrates it is possible to generate hiPSCs from ligament and identifies optimized ligament reprogramming conditions. ACL derived iPSCs may provide a promising cell source for ligament and related tissue engineering applications. \u00a9 2019 The Authors. <jats:italic>Journal of Orthopaedic Research<\/jats:italic>\u00ae published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:92\u2013104, 2020<\/jats:p>","DOI":"10.1002\/jor.24493","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T10:44:43Z","timestamp":1571136283000},"page":"92-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Generation of Human\u2010Induced Pluripotent Stem Cells From Anterior Cruciate Ligament"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-5722","authenticated-orcid":false,"given":"Steven","family":"Woods","sequence":"first","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences University of Manchester Michael Smith Building, Oxford Rd Manchester M13 9PT United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Bates","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences University of Manchester Michael Smith Building, Oxford Rd Manchester M13 9PT United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara L.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Division of Cell\u2010Matrix Biology and Regenerative Medicine, Wellcome Trust Centre for Cell\u2010Matrix Research, Faculty of Biology, Medicine and Health, School of Biological Sciences University of Manchester Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinand","family":"Serracino\u2010Inglott","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Central Manchester NHS Foundation Trust Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim E.","family":"Hardingham","sequence":"additional","affiliation":[{"name":"Division of Cell\u2010Matrix Biology and Regenerative Medicine, Wellcome Trust Centre for Cell\u2010Matrix Research, Faculty of Biology, Medicine and Health, School of Biological Sciences University of Manchester Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-6342","authenticated-orcid":false,"given":"Susan J.","family":"Kimber","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences University of Manchester Michael Smith Building, Oxford Rd Manchester M13 9PT United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151526"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.06.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011010106"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.09.008"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1503"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.086389"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23626"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.06.007"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30488"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4470"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.055889"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2011.01358.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v023a01"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09798"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002085"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008975"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1074"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1667"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09342"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.61"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2017.0017"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1683"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2019.101497"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3210"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2009.0716"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0561-y"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27229"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0215"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1123\/jsr.6.2.80"},{"key":"e_1_2_7_32_1","first-page":"CD005960","article-title":"Patellar tendon versus hamstring tendon autograft for anterior cruciate ligament rupture in adults","volume":"9","author":"Mohtadi NG","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.13.4894"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2013.0457"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02553"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01706"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.10.003"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1593"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22484"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.09.012"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.04.015"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0112-3"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1393"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201490649"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.12.001"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.24493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.24493","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T05:47:12Z","timestamp":1694238432000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.24493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,25]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/jor.24493"],"URL":"https:\/\/doi.org\/10.1002\/jor.24493","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,25]]},"assertion":[{"value":"2019-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}