{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:47:04Z","timestamp":1789469224592,"version":"build-2803163510"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":674,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"RETIC Program of ISCIII-FEDER","award":["RD16\/0011\/0005"],"award-info":[{"award-number":["RD16\/0011\/0005"]}]},{"name":"RETIC Program of ISCIII-FEDER","award":["RD16\/0011\/0013"],"award-info":[{"award-number":["RD16\/0011\/0013"]}]},{"name":"RETIC Program of ISCIII-FEDER","award":["RD16\/0011\/0015"],"award-info":[{"award-number":["RD16\/0011\/0015"]}]},{"name":"Spanish Ministry of Health and Consumer Affairs","award":["EC11\/074"],"award-info":[{"award-number":["EC11\/074"]}]},{"name":"Spanish Ministry of Health and Consumer Affairs","award":["EC11\/394"],"award-info":[{"award-number":["EC11\/394"]}]},{"name":"Spanish Ministry of Health and Consumer Affairs","award":["EC11\/260"],"award-info":[{"award-number":["EC11\/260"]}]},{"name":"RETIC Program of ISCIII-FEDER","award":["RD16\/0011\/0005"],"award-info":[{"award-number":["RD16\/0011\/0005"]}]},{"name":"RETIC Program of ISCIII-FEDER","award":["RD16\/0011\/0013"],"award-info":[{"award-number":["RD16\/0011\/0013"]}]},{"name":"RETIC Program of ISCIII-FEDER","award":["RD16\/0011\/0015"],"award-info":[{"award-number":["RD16\/0011\/0015"]}]},{"name":"Spanish Ministry of Health and Consumer Affairs","award":["EC11\/074"],"award-info":[{"award-number":["EC11\/074"]}]},{"name":"Spanish Ministry of Health and Consumer Affairs","award":["EC11\/394"],"award-info":[{"award-number":["EC11\/394"]}]},{"name":"Spanish Ministry of Health and Consumer Affairs","award":["EC11\/260"],"award-info":[{"award-number":["EC11\/260"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16\u2009weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52\u2009weeks and 2\u2009years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16\u2009weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52\u2009weeks. At the end of the study (2\u2009years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Significance statement Autologous mesenchymal stem cells treatment for complex perianal fistula is safe, but according to the current results, it seems to provide an advantage over a good surgical protocol at 2\u2009years after treatment and then results are similar to those shown with allogenic mesenchymal stem cells in previous clinical trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/sctm.19-0271","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T12:00:41Z","timestamp":1577707241000},"page":"295-301","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up"],"prefix":"10.1093","volume":"9","author":[{"given":"Mariano","family":"Garcia-Arranz","sequence":"first","affiliation":[{"name":"1 Department of Surgery and New Therapy Laboratory, Health Research Institute Fundaci\u00f3n Jim\u00e9nez D\u00edaz (FIIS-FJD) Universidad Aut\u00f3noma de Madrid (UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dami\u00e1n","family":"Garcia-Olmo","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and New Therapy Laboratory, Health Research Institute Fundaci\u00f3n Jim\u00e9nez D\u00edaz (FIIS-FJD) Universidad Aut\u00f3noma de Madrid (UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Herreros","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and New Therapy Laboratory, Health Research Institute Fundaci\u00f3n Jim\u00e9nez D\u00edaz (FIIS-FJD) Universidad Aut\u00f3noma de Madrid (UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Gracia-Solana","sequence":"additional","affiliation":[{"name":"2 Department of Colorectal Surgery, \u201cLozano Blesa\u201d University Hospital Aragon Health Sciences Institute, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Guadalajara","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and New Therapy Laboratory, Health Research Institute Fundaci\u00f3n Jim\u00e9nez D\u00edaz (FIIS-FJD) Universidad Aut\u00f3noma de Madrid (UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Portilla","sequence":"additional","affiliation":[{"name":"3 Coloproctology Unit, Gastrointestinal Surgery Department Virgen del Rocio University Hospital, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Baixauli","sequence":"additional","affiliation":[{"name":"4 Coloproctology Unit, Department of General and Digestive Surgery University Hospital of Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinto","family":"Garcia-Garcia","sequence":"additional","affiliation":[{"name":"5 Colorectal Surgery Unit, Department of General Surgery, Cl\u00ednica Universitaria de Navarra University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"2 Department of Colorectal Surgery, \u201cLozano Blesa\u201d University Hospital Aragon Health Sciences Institute, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferm\u00edn","family":"Sanchez-Guijo","sequence":"additional","affiliation":[{"name":"6 Cell Therapy Area, IBSAL-University Hospital, University of Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Prosper","sequence":"additional","affiliation":[{"name":"7 GMP Laboratory Cellular Therapy, Cl\u00ednica Universitaria de Navarra University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the FISPAC Collaborative Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"key":"2022022809191908300_sct312643-bib-0001","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00384-007-0334-7","article-title":"An assessment of the incidence of fistula-in-ano in four countries of the European Union","volume":"22","author":"Zanotti","year":"2007","journal-title":"Int J Colorectal Dis"},{"key":"2022022809191908300_sct312643-bib-0002","first-page":"219","article-title":"Fistula-in-ano in a defined population: incidence and epidemiological aspects","volume":"73","author":"Sainio","year":"1984","journal-title":"Ann Chir Gynaecol"},{"key":"2022022809191908300_sct312643-bib-0003","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1007\/BF02237422","article-title":"Patient satisfaction after surgical treatment for fistula-in-ano","volume":"43","author":"Garcia-Aguilar","year":"2000","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0004","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s10350-005-0055-3","article-title":"Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised)","volume":"48","author":"Whiteford","year":"2005","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0005","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/BF02236199","article-title":"Patient and surgeon ranking of the severity of symptoms associated with fecal incontinence: the fecal incontinence severity index","volume":"42","author":"Rockwood","year":"1999","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0006","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00384-003-0490-3","article-title":"Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy","volume":"18","author":"Garc\u00eda-Olmo","year":"2003","journal-title":"Int J Colorectal Dis"},{"key":"2022022809191908300_sct312643-bib-0007","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1053\/j.gastro.2008.11.041","article-title":"Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses","volume":"136","author":"Gonzalez","year":"2009","journal-title":"Gastroenterology"},{"key":"2022022809191908300_sct312643-bib-0008","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/01.SAP.0000029661.38066.15","article-title":"Future of fat as raw material for tissue regeneration","volume":"50","author":"De Ugarte","year":"2003","journal-title":"Ann Plast Surg"},{"key":"2022022809191908300_sct312643-bib-0009","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1365-2141.2005.05409.x","article-title":"Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells","volume":"129","author":"Puissant","year":"2005","journal-title":"Br J Haematol"},{"key":"2022022809191908300_sct312643-bib-0010","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1007\/s10350-005-0052-6","article-title":"A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation","volume":"48","author":"Garcia-Olmo","year":"2005","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0011","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/DCR.0b013e3181973487","article-title":"Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial","volume":"52","author":"Garcia-Olmo","year":"2009","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0012","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00384-011-1350-1","article-title":"Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas","volume":"27","author":"Guadalajara","year":"2012","journal-title":"Int J Colorectal Dis"},{"key":"2022022809191908300_sct312643-bib-0013","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1097\/DCR.0b013e318255364a","article-title":"Autologous expanded adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistulas: a phase III randomized clinical trial (FATT 1: fistula advanced therapy trial 1) and long-term evaluation","volume":"55","author":"Herreros","year":"2012","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0014","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/S0140-6736(16)31203-X","article-title":"Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial","volume":"388","author":"Pan\u00e9s","year":"2016","journal-title":"Lancet"},{"key":"2022022809191908300_sct312643-bib-0015","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1053\/j.gastro.2017.12.020","article-title":"Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn's disease","volume":"154","author":"Pan\u00e9s","year":"2018","journal-title":"Gastroenterology"},{"key":"2022022809191908300_sct312643-bib-0016","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s11605-018-3895-6","article-title":"A step-by-step surgical protocol for the treatment of perianal fistula with adipose-derived mesenchymal stem cells","volume":"22","author":"Georgiev-Hristov","year":"2018","journal-title":"J Gastrointest Surg"},{"key":"2022022809191908300_sct312643-bib-0017","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.jcyt.2017.03.076","article-title":"Regulatory perspective on in vitro potency assays for human mesenchymal stromal cells used in immunotherapy","volume":"19","author":"Wolf","year":"2017","journal-title":"Cytotherapy"},{"key":"2022022809191908300_sct312643-bib-0018","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1517\/14712598.2010.519333","article-title":"Mesenchymal stem cells: biological properties and clinical applications","volume":"10","author":"Garc\u00eda-G\u00f3mez","year":"2010","journal-title":"Expert Opin Biol Ther"},{"key":"2022022809191908300_sct312643-bib-0019","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ymeth.2015.09.016","article-title":"Mesenchymal stem cells: identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche","volume":"99","author":"Kobolak","year":"2016","journal-title":"Methods"},{"key":"2022022809191908300_sct312643-bib-0020","first-page":"876","article-title":"The role of fibrin glue in the treatment of high and low fistulas in ano","volume":"7","author":"Mishra","year":"2013","journal-title":"J Clin Diagn Res"},{"key":"2022022809191908300_sct312643-bib-0021","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/5901479","article-title":"Long-lasting anti-inflammatory activity of human microfragmented adipose tissue","volume":"2019","author":"Nava","year":"2019","journal-title":"Stem Cells Int"},{"key":"2022022809191908300_sct312643-bib-0022","doi-asserted-by":"crossref","first-page":"9057","DOI":"10.3748\/wjg.v22.i41.9057","article-title":"Mesenchymal stromal cell-based therapy: regulatory and translational aspects in gastroenterology","volume":"22","author":"Dothel","year":"2016","journal-title":"World J Gastroenterol"},{"key":"2022022809191908300_sct312643-bib-0023","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13287-016-0352-x","article-title":"Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem\/stromal cells: present and future","volume":"7","author":"Giuseppe","year":"2016","journal-title":"Stem Cell Res Ther"},{"key":"2022022809191908300_sct312643-bib-0024","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.amsu.2017.10.023","article-title":"Off-label use of adipose-derived stem cells","volume":"24","author":"Simonacci","year":"2017","journal-title":"Ann Med Surg"},{"key":"2022022809191908300_sct312643-bib-0025","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-30772-4","article-title":"Evaluation of platelet lysate as a substitute for FBS in explant and enzymatic isolation methods of human umbilical cord MSCs","volume":"8","author":"Kandoi","year":"2018","journal-title":"Sci Rep"},{"key":"2022022809191908300_sct312643-bib-0026","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13287-018-0863-8","article-title":"Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience","volume":"9","author":"Becherucci","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"2022022809191908300_sct312643-bib-0027","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1038\/s41598-017-05207-1","article-title":"Human platelet lysate versus fetal calf serum: these supplements do not select for different mesenchymal stromal cells","volume":"7","author":"Fernandez-Rebollo","year":"2017","journal-title":"Sci Rep"},{"key":"2022022809191908300_sct312643-bib-0028","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1159\/000492581","article-title":"Comparative analysis of biological and functional properties of bone marrow mesenchymal stromal cells expanded in media with different platelet lysate content","volume":"205","author":"Skific","year":"2018","journal-title":"Cells Tissues Organs"},{"key":"2022022809191908300_sct312643-bib-0029","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/DCR.0000000000001093","article-title":"A systematic review and meta-analysis of mesenchymal stem cell injections for the treatment of perianal Crohn's disease: progress made and future directions","volume":"61","author":"Lightner","year":"2018","journal-title":"Dis Colon Rectum"},{"key":"2022022809191908300_sct312643-bib-0030","doi-asserted-by":"crossref","first-page":"532","DOI":"10.5966\/sctm.2014-0199","article-title":"Long-term results of adipose-derived stem cell therapy for the treatment of Crohn's fistula","volume":"4","author":"Cho","year":"2015","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022809191908300_sct312643-bib-0031","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/6289825","article-title":"Mesenchymal stem cells after polytrauma: actor and target","volume":"2016","author":"Huber-Lang","year":"2016","journal-title":"Stem Cells Int"},{"key":"2022022809191908300_sct312643-bib-0032","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s11033-018-4516-x","article-title":"Mesenchymal stem cell dysfunction in diabetes","volume":"46","author":"Fijany","year":"2019","journal-title":"Mol Biol Rep"},{"key":"2022022809191908300_sct312643-bib-0033","doi-asserted-by":"crossref","first-page":"698","DOI":"10.3109\/14653240903051558","article-title":"Mesenchymal stem cells are functionally abnormal in patients with immune thrombocytopenic purpura","volume":"11","author":"P\u00e9rez-Sim\u00f3n","year":"2009","journal-title":"Cytotherapy"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsctm.19-0271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sctm.19-0271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sctm.19-0271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/3\/295\/42628110\/stcltm_9_3_295.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/3\/295\/42628110\/stcltm_9_3_295.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:20:48Z","timestamp":1646040048000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/9\/3\/295\/6407132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,30]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,12,30]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.19-0271","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,1]]},"published":{"date-parts":[[2019,12,30]]},"assertion":[{"value":"2019-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}