{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:41:58Z","timestamp":1787794918873,"version":"build-2784847793"},"reference-count":162,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Between 20 to 25% of Crohn\u2019s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNF\u03b1 can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem\/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel\u00ae) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.<\/jats:p>","DOI":"10.3390\/ijms22189967","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:00:44Z","timestamp":1631707244000},"page":"9967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn\u2019s Disease: Rationale, Clinical Results and Perspectives"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-3045","authenticated-orcid":false,"given":"Etienne","family":"Buscail","sequence":"first","affiliation":[{"name":"Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France"},{"name":"IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8416-5432","authenticated-orcid":false,"given":"Guillaume","family":"Le Cosquer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0249-6404","authenticated-orcid":false,"given":"Fabian","family":"Gross","sequence":"additional","affiliation":[{"name":"Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Lebrin","sequence":"additional","affiliation":[{"name":"Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Bugarel","sequence":"additional","affiliation":[{"name":"Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Deraison","sequence":"additional","affiliation":[{"name":"IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Vergnolle","sequence":"additional","affiliation":[{"name":"IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bournet","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrielle","family":"Gilletta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4276-1003","authenticated-orcid":false,"given":"Louis","family":"Buscail","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France"},{"name":"Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1053\/j.gastro.2005.12.019","article-title":"Predictors of Crohn\u2019s Disease","volume":"130","author":"Beaugerie","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/apt.12894","article-title":"Anorectal Stricture in 102 Patients with Crohn\u2019s Disease: Natural History in the Era of Biologics","volume":"40","author":"Brochard","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1053\/gast.2002.32362","article-title":"The Natural History of Fistulizing Crohn\u2019s Disease in Olmsted County, Minnesota","volume":"122","author":"Schwartz","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.cgh.2016.04.031","article-title":"Cumulative Length of Bowel Resection in a Population-Based Cohort of Patients With Crohn\u2019s Disease","volume":"14","author":"Harmsen","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.dld.2017.07.014","article-title":"Anal Ulcerations in Crohn\u2019s Disease: Natural History in the Era of Biological Therapy","volume":"49","author":"Wallenhorst","year":"2017","journal-title":"Dig. Liver Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100808","DOI":"10.1016\/j.cpsurg.2020.100808","article-title":"Fistulizing Crohn\u2019s Disease","volume":"57","author":"Lightner","year":"2020","journal-title":"Curr. Probl. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.gastro.2003.08.025","article-title":"American Gastroenterological Association Clinical Practice Committee. AGA Technical Review on Perianal Crohn\u2019s Disease","volume":"125","author":"Sandborn","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1097\/MIB.0000000000000148","article-title":"Disappointing Durable Remission Rates in Complex Crohn\u2019s Disease Fistula","volume":"20","author":"Molendijk","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/apt.13835","article-title":"Therapeutic Management of Inflammatory Bowel Disease in Real-Life Practice in the Current Era of Anti-TNF Agents: Analysis of the French Administrative Health Databases 2009\u20132014","volume":"45","author":"Kirchgesner","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/MIB.0000000000000315","article-title":"Crohn\u2019s & Colitis Foundation of America, Inc. Guidelines for the Multidisciplinary Management of Crohn\u2019s Perianal Fistulas: Summary Statement","volume":"21","author":"Schwartz","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1056\/NEJM199905063401804","article-title":"Infliximab for the Treatment of Fistulas in Patients with Crohn\u2019s Disease","volume":"340","author":"Present","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1056\/NEJMoa030815","article-title":"Infliximab Maintenance Therapy for Fistulizing Crohn\u2019s Disease","volume":"350","author":"Sands","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/apt.12499","article-title":"Adalimumab Maintains Remission of Crohn\u2019s Disease after up to 4 Years of Treatment: Data from CHARM and ADHERE","volume":"38","author":"Panaccione","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/ibd.21405","article-title":"Combined Approach with Infliximab, Surgery, and Methotrexate in Severe Fistulizing Anoperineal Crohn\u2019s Disease: Results from a Prospective Study","volume":"17","author":"Bouchard","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/apt.13970","article-title":"Higher Infliximab Trough Levels Are Associated with Perianal Fistula Healing in Patients with Crohn\u2019s Disease","volume":"45","author":"Yarur","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_16","first-page":"975","article-title":"Long-Term Outcome of Perianal Fistulizing Crohn\u2019s Disease Treated with Infliximab","volume":"11","author":"Bouguen","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/codi.12851","article-title":"The Results of Seton Drainage Combined with Anti-TNF\u03b1 Therapy for Anal Fistula in Crohn\u2019s Disease","volume":"17","author":"Haennig","year":"2015","journal-title":"Colorectal Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1097\/MIB.0b013e318281327f","article-title":"Experiences of Fecal Incontinence in People with Inflammatory Bowel Disease: Self-Reported Experiences among a Community Sample","volume":"19","author":"Dibley","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/DCR.0b013e3182099d9e","article-title":"Quality of Life in Perianal Crohn\u2019s Disease: What Do Patients Consider Important?","volume":"54","author":"Mahadev","year":"2011","journal-title":"Dis. Colon Rectum"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1089\/hum.2016.095","article-title":"Mesenchymal Stem Cells to Treat Crohn\u2019s Disease with Fistula","volume":"28","author":"Zhang","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/apt.13864","article-title":"Review Article: Mesenchymal Stromal Cell Therapy for Inflammatory Bowel Diseases","volume":"45","author":"Lechanteur","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13287-017-0570-x","article-title":"Systematic Review with Meta-Analysis: The Efficacy and Safety of Stem Cell Therapy for Crohn\u2019s Disease","volume":"8","author":"Qiu","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_23","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\u2019s Disease: Progress Made and Future Directions","volume":"61","author":"Lightner","year":"2018","journal-title":"Dis. Colon Rectum"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10151-019-01994-z","article-title":"The Clinical Efficacy of Stem Cell Therapy for Complex Perianal Fistulas: A Meta-Analysis","volume":"23","author":"Choi","year":"2019","journal-title":"Tech. Coloproctol"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gallo, G., Tiesi, V., Fulginiti, S., De Paola, G., Vescio, G., and Sammarco, G. (2020). Mesenchymal Stromal Cell Therapy in the Management of Perianal Fistulas in Crohn\u2019s Disease: An Up-To-Date Review. Med. Kaunas Lith., 56.","DOI":"10.3390\/medicina56110563"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.jcyt.2013.02.006","article-title":"Stromal Cells from the Adipose Tissue-Derived Stromal Vascular Fraction and Culture Expanded Adipose Tissue-Derived Stromal\/Stem Cells: A Joint Statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT)","volume":"15","author":"Bourin","year":"2013","journal-title":"Cytotherapy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"822","DOI":"10.3332\/ecancer.2018.822","article-title":"Adipose Tissue Stem Cells in Regenerative Medicine","volume":"12","author":"Miana","year":"2018","journal-title":"Ecancermedicalscience"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Carvello, M., Lightner, A., Yamamoto, T., Kotze, P.G., and Spinelli, A. (2019). Mesenchymal Stem Cells for Perianal Crohn\u2019s Disease. Cells, 8.","DOI":"10.3390\/cells8070764"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lombardi, F., Palumbo, P., Augello, F.R., Cifone, M.G., Cinque, B., and Giuliani, M. (2019). Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153721"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4252\/wjsc.v9.i8.107","article-title":"Adipose-Derived Stromal Cell in Regenerative Medicine: A Review","volume":"9","author":"Qomi","year":"2017","journal-title":"World J. Stem Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/BF02253493","article-title":"Clinical Classification of Perianal Crohn\u2019s Disease","volume":"35","author":"Hughes","year":"1992","journal-title":"Dis. Colon Rectum"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/17474124.2018.1480936","article-title":"Clinical Updates on Perianal Fistulas in Crohn\u2019s Disease","volume":"12","author":"Rackovsky","year":"2018","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/00004836-199501000-00008","article-title":"Usual Therapy Improves Perianal Crohn\u2019s Disease as Measured by a New Disease Activity Index. McMaster IBD Study Group","volume":"20","author":"Irvine","year":"1995","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.3748\/wjg.v23.i29.5371","article-title":"Elaboration and Validation of Crohn\u2019s Disease Anoperineal Lesions Consensual Definitions","volume":"23","author":"Horaist","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.cgh.2010.01.001","article-title":"Correlation between the Crohn\u2019s Disease Activity and Harvey-Bradshaw Indices in Assessing Crohn\u2019s Disease Severity","volume":"8","author":"Vermeire","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0002-9270(02)05909-9","article-title":"Magnetic Resonance Imaging of the Effects of Infliximab on Perianal Fistulizing Crohn\u2019s Disease","volume":"98","author":"Vanbeckevoort","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.dld.2014.08.003","article-title":"Magnetic Resonance Imaging and Clinical Assessments for Perianal Crohn\u2019s Disease: Gain and Limits","volume":"46","author":"Garros","year":"2014","journal-title":"Dig. Liver Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.3748\/wjg.v23.i23.4285","article-title":"Magnetic Resonance Imaging May Predict Deep Remission in Patients with Perianal Fistulizing Crohn\u2019s Disease","volume":"23","author":"Thomassin","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/bjs.4466","article-title":"Long-Term Outcome Following Loose-Seton Technique for External Sphincter Preservation in Complex Anal Fistula","volume":"91","author":"Buchanan","year":"2004","journal-title":"Br. J. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/bjs.6608","article-title":"Outcome of Surgical Treatment for Fistula in Ano in Crohn\u2019s Disease","volume":"96","author":"Safiruddin","year":"2009","journal-title":"Br. J. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/DCR.0b013e3181ce8b01","article-title":"Endorectal Advancement Flap for Cryptoglandular or Crohn\u2019s Fistula-in-Ano","volume":"53","author":"Soltani","year":"2010","journal-title":"Dis. Colon Rectum"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/bjs5.13","article-title":"ENiGMA Collaborators. Systematic Review of Surgical Interventions for Crohn\u2019s Anal Fistula","volume":"1","author":"Lee","year":"2017","journal-title":"BJS Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1053\/j.gastro.2010.02.013","article-title":"Fibrin Glue Is Effective Healing Perianal Fistulas in Patients with Crohn\u2019s Disease","volume":"138","author":"Grimaud","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/ecco-jcc\/jjv162","article-title":"Fistula Plug in Fistulising Ano-Perineal Crohn\u2019s Disease: A Randomised Controlled Trial","volume":"10","author":"Siproudhis","year":"2016","journal-title":"J. Crohns Colitis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1002\/bjs.10549","article-title":"Randomized Clinical Trial Comparing Collagen Plug and Advancement Flap for Trans-Sphincteric Anal Fistula","volume":"104","author":"Bondi","year":"2017","journal-title":"Br. J. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.cgh.2014.08.038","article-title":"Placebo Response Rate in Clinical Trials of Fistulizing Crohn\u2019s Disease: Systematic Review and Meta-Analysis","volume":"12","author":"Ford","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"765","DOI":"10.5114\/aoms.2013.38670","article-title":"Tumor Necrosis Factor-\u03b1 Antibodies (Infliximab, Adalimumab and Certolizumab) in Crohn\u2019s Disease: Systematic Review and Meta-Analysis","volume":"9","author":"Kawalec","year":"2013","journal-title":"Arch. Med. Sci. AMS"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1007\/s10620-008-0545-y","article-title":"Predicting Factors of Fistula Healing and Clinical Remission after Infliximab-Based Combined Therapy for Perianal Fistulizing Crohn\u2019s Disease","volume":"54","author":"Tougeron","year":"2009","journal-title":"Dig. Dis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/gut.2008.159251","article-title":"Adalimumab for the Treatment of Fistulas in Patients with Crohn\u2019s Disease","volume":"58","author":"Colombel","year":"2009","journal-title":"Gut"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1463-1318.2004.00749.x","article-title":"Infliximab in the Surgical Management of Complex Fistulating Anal Crohn\u2019s Disease","volume":"7","author":"Talbot","year":"2005","journal-title":"Colorectal Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10350-004-6611-4","article-title":"Combined Seton Placement, Infliximab Infusion, and Maintenance Immunosuppressives Improve Healing Rate in Fistulizing Anorectal Crohn\u2019s Disease: A Single Center Experience","volume":"46","author":"Topstad","year":"2003","journal-title":"Dis. Colon Rectum"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/00054725-200303000-00003","article-title":"Treatment of Perianal Fistulizing Crohn\u2019s Disease with Infliximab Alone or as an Adjunct to Exam under Anesthesia with Seton Placement","volume":"9","author":"Regueiro","year":"2003","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s10350-006-0656-5","article-title":"Fistulating Anal Crohn\u2019s Disease: Results of Combined Surgical and Infliximab Treatment","volume":"49","author":"Hyder","year":"2006","journal-title":"Dis. Colon Rectum"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10151-008-0411-0","article-title":"Combined Therapy with Infliximab and Seton Drainage for Perianal Fistulizing Crohn\u2019s Disease with Anal Endosonographic Monitoring: A Single-Centre Experience","volume":"12","author":"Guidi","year":"2008","journal-title":"Tech. Coloproctol."},{"key":"ref_55","first-page":"3","article-title":"Clinical Advantages of Combined Seton Placement and Infliximab Maintenance Therapy for Perianal Fistulizing Crohn\u2019s Disease: When and How Were the Seton Drains Removed?","volume":"57","author":"Tanaka","year":"2010","journal-title":"Hepatogastroenterology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/codi.13311","article-title":"Treatment of Perianal Fistula in Crohn\u2019s Disease: A Systematic Review and Meta-Analysis Comparing Seton Drainage and Anti-Tumour Necrosis Factor Treatment","volume":"18","author":"Sahami","year":"2016","journal-title":"Colorectal Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/j.cgh.2018.01.030","article-title":"Efficacy of Medical Therapies for Fistulizing Crohn\u2019s Disease: Systematic Review and Meta-Analysis","volume":"16","author":"Lee","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/apt.15665","article-title":"Vedolizumab for Perianal Crohn\u2019s Disease: A Multicentre Cohort Study in 151 Patients","volume":"51","author":"Bourrier","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/apt.15688","article-title":"Editorial: Is Vedolizumab Effective for Perianal Crohn\u2019s Disease?","volume":"51","author":"Ungar","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00535-018-1449-z","article-title":"New Treatment Options for Inflammatory Bowel Diseases","volume":"53","author":"Verstockt","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/ajg.2016.236","article-title":"The Real-World Effectiveness and Safety of Vedolizumab for Moderate-Severe Crohn\u2019s Disease: Results From the US VICTORY Consortium","volume":"111","author":"Dulai","year":"2016","journal-title":"Am. J. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.14309\/ajg.0000000000000810","article-title":"Ustekinumab for Perianal Crohn\u2019s Disease: The BioLAP Multicenter Study From the GETAID","volume":"115","author":"Kirchgesner","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/ecco-jcc\/jjz119","article-title":"Ustekinumab for Crohn\u2019s Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study","volume":"14","author":"Biemans","year":"2020","journal-title":"J. Crohns Colitis"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1097\/SLA.0000000000001461","article-title":"Rectovaginal Fistula: What Is the Optimal Strategy?: An Analysis of 79 Patients Undergoing 286 Procedures","volume":"262","author":"Corte","year":"2015","journal-title":"Ann. Surg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1007\/s10350-007-9057-7","article-title":"Rectovaginal Fistula in Crohn\u2019s Disease","volume":"50","author":"Andreani","year":"2007","journal-title":"Dis. Colon Rectum"},{"key":"ref_66","first-page":"912","article-title":"Long-Term Treatment of Rectovaginal Fistulas in Crohn\u2019s Disease: Response to Infliximab in the ACCENT II Study","volume":"2","author":"Sands","year":"2004","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_67","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\u2019s Disease: A Phase 3 Randomised, Double-Blind Controlled Trial","volume":"388","author":"Colombel","year":"2016","journal-title":"Lancet"},{"key":"ref_68","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\u2019s Disease","volume":"154","author":"Colombel","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"132","DOI":"10.2302\/kjm.54.132","article-title":"Multipotential Differentiation of Adipose Tissue-Derived Stem Cells","volume":"54","author":"Strem","year":"2005","journal-title":"Keio J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1038\/ncpcardio0444","article-title":"Plasticity of Human Adipose Stem Cells toward Endothelial Cells and Cardiomyocytes","volume":"3","author":"Fraser","year":"2006","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_72","first-page":"261","article-title":"Human mesenchymal stem cell biology","volume":"27","author":"Charbord","year":"2011","journal-title":"Med. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.cryobiol.2015.07.003","article-title":"Mesenchymal Stromal Cells Derived from Various Tissues: Biological, Clinical and Cryopreservation Aspects","volume":"71","author":"McGann","year":"2015","journal-title":"Cryobiology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1089\/scd.2011.0722","article-title":"Same or Not the Same? Comparison of Adipose Tissue-Derived versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells","volume":"21","author":"Strioga","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1634\/stemcells.2005-0342","article-title":"Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue","volume":"24","author":"Kern","year":"2006","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/14653240500319234","article-title":"Clarification of the Nomenclature for MSC: The International Society for Cellular Therapy Position Statement","volume":"7","author":"Horwitz","year":"2005","journal-title":"Cytotherapy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. The International Society for Cellular Therapy Position Statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/sctm.17-0051","article-title":"Mesenchymal Stem Cells: Time to Change the Name","volume":"6","author":"Caplan","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/jbm.a.36243","article-title":"Colorectal Wall Regeneration Resulting from the Association of Chitosan Hydrogel and Stromal Vascular Fraction from Adipose Tissue","volume":"106","author":"Denost","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/ten.teb.2011.0488","article-title":"Therapeutic Applications of Mesenchymal Stromal Cells: Paracrine Effects and Potential Improvements","volume":"18","author":"Doorn","year":"2012","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1634\/stemcells.2005-0234","article-title":"Immunophenotype of Human Adipose-Derived Cells: Temporal Changes in Stromal-Associated and Stem Cell-Associated Markers","volume":"24","author":"Mitchell","year":"2006","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Gentile, P., Calabrese, C., De Angelis, B., Pizzicannella, J., Kothari, A., and Garcovich, S. (2019). Impact of the Different Preparation Methods to Obtain Human Adipose-Derived Stromal Vascular Fraction Cells (AD-SVFs) and Human Adipose-Derived Mesenchymal Stem Cells (AD-MSCs): Enzymatic Digestion Versus Mechanical Centrifugation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215471"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Liu, S., Zhou, J., Zhang, X., Liu, Y., Chen, J., Hu, B., Song, J., and Zhang, Y. (2016). Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060982"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1634\/stemcells.2004-0021","article-title":"Cell Surface and Transcriptional Characterization of Human Adipose-Derived Adherent Stromal (HADAS) Cells","volume":"23","author":"Katz","year":"2005","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/jcp.1138","article-title":"Surface Protein Characterization of Human Adipose Tissue-Derived Stromal Cells","volume":"189","author":"Gronthos","year":"2001","journal-title":"J. Cell. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1089\/ten.tea.2009.0621","article-title":"Differential Gene Expression in Adipose Stem Cells Cultured in Allogeneic Human Serum versus Fetal Bovine Serum","volume":"16","author":"Lindroos","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/jcp.21210","article-title":"Multipotential Human Adipose-Derived Stromal Stem Cells Exhibit a Perivascular Phenotype in vitro and in vivo","volume":"214","author":"Zannettino","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3109\/14653240903233081","article-title":"Serum-Free, Xeno-Free Culture Media Maintain the Proliferation Rate and Multipotentiality of Adipose Stem Cells in vitro","volume":"11","author":"Lindroos","year":"2009","journal-title":"Cytotherapy"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1080\/14653240701508452","article-title":"Low Serum and Serum-Free Culture of Multipotential Human Adipose Stem Cells","volume":"9","author":"Parker","year":"2007","journal-title":"Cytotherapy"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13287-018-1069-9","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Affect Disease Outcomes via Transfer of MicroRNAs","volume":"9","author":"Qiu","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00441-018-2871-5","article-title":"Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Regenerative and Immunomodulatory Effects and Potential Applications in Sepsis","volume":"374","author":"Zheng","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1681\/ASN.2008070798","article-title":"Mesenchymal Stem Cell-Derived Microvesicles Protect against Acute Tubular Injury","volume":"20","author":"Bruno","year":"2009","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.ajpath.2012.08.009","article-title":"Network Analysis of Transcriptional Responses Induced by Mesenchymal Stem Cell Treatment of Experimental Sepsis","volume":"181","author":"Murthy","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/scrt428","article-title":"Microvesicles Derived from Human Wharton\u2019s Jelly Mesenchymal Stromal Cells Ameliorate Renal Ischemia-Reperfusion Injury in Rats by Suppressing CX3CL1","volume":"5","author":"Zou","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.3390\/ijms16034581","article-title":"Recent Advances in Proteomic Studies of Adipose Tissues and Adipocytes","volume":"16","author":"Kim","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"191","DOI":"10.5114\/aoms.2013.33181","article-title":"Biochemistry of Adipose Tissue: An Endocrine Organ","volume":"9","author":"Coelho","year":"2013","journal-title":"Arch. Med. Sci. AMS"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1002\/stem.2372","article-title":"Mitochondrial Transfer via Tunneling Nanotubes Is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS","volume":"34","author":"Jackson","year":"2016","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.108.176826","article-title":"Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy","volume":"103","author":"Gnecchi","year":"2008","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Dubey, N.K., Mishra, V.K., Dubey, R., Deng, Y.-H., Tsai, F.-C., and Deng, W.-P. (2018). Revisiting the Advances in Isolation, Characterization and Secretome of Adipose-Derived Stromal\/Stem Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082200"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1186\/s13287-020-01975-2","article-title":"Human Adipose Mesenchymal Stem Cells Modulate Myeloid Cells toward an Anti-Inflammatory and Reparative Phenotype: Role of IL-6 and PGE2","volume":"11","author":"Menta","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1161\/01.CIR.0000121425.42966.F1","article-title":"Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells","volume":"109","author":"Rehman","year":"2004","journal-title":"Circulation"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"237","DOI":"10.5999\/aps.2016.43.3.237","article-title":"Melatonin Protects Human Adipose-Derived Stem Cells from Oxidative Stress and Cell Death","volume":"43","author":"Tan","year":"2016","journal-title":"Arch. Plast. Surg."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10561-007-9048-x","article-title":"Human Platelet Lysate Enhances the Proliferative Activity of Cultured Human Fibroblast-like Cells from Different Tissues","volume":"9","author":"Mirabet","year":"2008","journal-title":"Cell Tissue Bank."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/icb.2012.56","article-title":"Mechanisms of Mesenchymal Stromal Cell Immunomodulation","volume":"91","author":"English","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1365-2249.2007.03422.x","article-title":"Interferon-Gamma Does Not Break, but Promotes the Immunosuppressive Capacity of Adult Human Mesenchymal Stem Cells","volume":"149","author":"Ryan","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nbt.2816","article-title":"Mesenchymal Stem Cells: Immune Evasive, Not Immune Privileged","volume":"32","author":"Ankrum","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1089\/scd.2011.0139","article-title":"Human Adipose-Derived Stem Cells Impair Natural Killer Cell Function and Exhibit Low Susceptibility to Natural Killer-Mediated Lysis","volume":"21","author":"DelaRosa","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/cmi.12522","article-title":"Antibacterial Effect of Mesenchymal Stem Cells against Escherichia Coli Is Mediated by Secretion of Beta- Defensin- 2 via Toll- like Receptor 4 Signalling","volume":"18","author":"Sung","year":"2016","journal-title":"Cell. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1002\/stem.1996","article-title":"Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Pulmonary Infection Caused by Pseudomonas Aeruginosa via Inhibiting Overproduction of Prostaglandin E2","volume":"33","author":"Mao","year":"2015","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1111\/jcmm.12610","article-title":"Melatonin Protects ADSCs from ROS and Enhances Their Therapeutic Potency in a Rat Model of Myocardial Infarction","volume":"19","author":"Zhu","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Cousin, B., Ravet, E., Poglio, S., De Toni, F., Bertuzzi, M., Lulka, H., Touil, I., Andr\u00e9, M., Grolleau, J.-L., and P\u00e9ron, J.-M. (2009). Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death Both in vitro and in vivo. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006278"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.exphem.2005.07.003","article-title":"Comparative Characteristics of Mesenchymal Stem Cells from Human Bone Marrow, Adipose Tissue, and Umbilical Cord Blood","volume":"33","author":"Wagner","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1002\/jcb.20904","article-title":"Biologic Properties of Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissue","volume":"99","author":"Izadpanah","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1089\/scd.2007.0154","article-title":"Comparison of Human Placenta- and Bone Marrow-Derived Multipotent Mesenchymal Stem Cells","volume":"17","author":"Barlow","year":"2008","journal-title":"Stem Cells Dev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1177\/0963689717721203","article-title":"Impact of Age on Human Adipose Stem Cells for Bone Tissue Engineering","volume":"26","author":"Dufrane","year":"2017","journal-title":"Cell Transplant."},{"key":"ref_116","first-page":"105698","article-title":"Comparative Analysis of Apoptotic Resistance of Mesenchymal Stem Cells Isolated from Human Bone Marrow and Adipose Tissue","volume":"2012","author":"Ural","year":"2012","journal-title":"Sci. World J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"455","DOI":"10.5966\/sctm.2012-0184","article-title":"Adipose Tissue-Derived Multipotent Stromal Cells Have a Higher Immunomodulatory Capacity than Their Bone Marrow-Derived Counterparts","volume":"2","author":"Melief","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/14712598.2019.1623876","article-title":"Cx601 (Darvadstrocel) for the Treatment of Perianal Fistulizing Crohn\u2019s Disease","volume":"19","author":"Bislenghi","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.3389\/fimmu.2019.01244","article-title":"Dissecting Allo-Sensitization After Local Administration of Human Allogeneic Adipose Mesenchymal Stem Cells in Perianal Fistulas of Crohn\u2019s Disease Patients","volume":"10","author":"Menta","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/sctm.17-0040","article-title":"Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study","volume":"6","author":"Kastrup","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.ijcard.2016.02.016","article-title":"Intramyocardial Transplantation of Mesenchymal Stromal Cells for Chronic Myocardial Ischemia and Impaired Left Ventricular Function: Results of the MESAMI 1 Pilot Trial","volume":"209","author":"Guijarro","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jcyt.2013.11.011","article-title":"Phase I Trial: The Use of Autologous Cultured Adipose-Derived Stroma\/Stem Cells to Treat Patients with Non-Revascularizable Critical Limb Ischemia","volume":"16","author":"Bura","year":"2014","journal-title":"Cytotherapy"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Takahashi, H., Sakata, N., Yoshimatsu, G., Hasegawa, S., and Kodama, S. (2019). Regenerative and Transplantation Medicine: Cellular Therapy Using Adipose Tissue-Derived Mesenchymal Stromal Cells for Type 1 Diabetes Mellitus. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020249"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"847","DOI":"10.5966\/sctm.2015-0245","article-title":"Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial","volume":"5","author":"Pers","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.joca.2013.06.025","article-title":"Safety of Intra-Articular Cell-Therapy with Culture-Expanded Stem Cells in Humans: A Systematic Literature Review","volume":"21","author":"Peeters","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2217\/rme-2018-0161","article-title":"Adipose-Derived Mesenchymal Stem Cell Therapy in the Treatment of Knee Osteoarthritis: A Randomized Controlled Trial","volume":"14","author":"Freitag","year":"2019","journal-title":"Regen. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12974-018-1099-3","article-title":"Adipose Stromal Vascular Fraction Attenuates TH1 Cell-Mediated Pathology in a Model of Multiple Sclerosis","volume":"15","author":"Bowles","year":"2018","journal-title":"J. Neuroinflam."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4197857","DOI":"10.1155\/2018\/4197857","article-title":"Current Perspectives Regarding Stem Cell-Based Therapy for Liver Cirrhosis","volume":"2018","author":"Kwak","year":"2018","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jcyt.2017.05.002","article-title":"Adipose Tissue-Derived Mesenchymal Stromal Cells as Part of Therapy for Chronic Graft-versus-Host Disease: A Phase I\/II Study","volume":"19","author":"Jurado","year":"2017","journal-title":"Cytotherapy"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12967-020-02380-2","article-title":"Rationale for the Clinical Use of Adipose-Derived Mesenchymal Stem Cells for COVID-19 Patients","volume":"18","author":"Rogers","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1002\/sctm.17-0031","article-title":"Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events","volume":"6","author":"Toyserkani","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"11823","DOI":"10.2147\/CMAR.S277130","article-title":"Adipose-Derived Stem Cells Promote Proliferation and Invasion in Cervical Cancer by Targeting the HGF\/c-MET Pathway","volume":"12","author":"Zhai","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Scioli, M.G., Storti, G., D\u2019Amico, F., Gentile, P., Kim, B.-S., Cervelli, V., and Orlandi, A. (2019). Adipose-Derived Stem Cells in Cancer Progression: New Perspectives and Opportunities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133296"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/stem.3050","article-title":"Adipose Stem Cells and Cancer: Concise Review","volume":"37","author":"Sabol","year":"2019","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Ejaz, A., Yang, K.S., Venkatesh, K.P., Chinnapaka, S., Kokai, L.E., and Rubin, J.P. (2020). The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239171"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/00365521.2017.1281434","article-title":"Local Application of Adipose-Derived Mesenchymal Stem Cells Supports the Healing of Fistula: Prospective Randomised Study on Rat Model of Fistulising Crohn\u2019s Disease","volume":"52","author":"Ryska","year":"2017","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s10620-017-4453-x","article-title":"Efficacy of Mesenchymal Stromal Cells for Fistula Treatment of Crohn\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"62","author":"Cao","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"8816737","DOI":"10.1155\/2020\/8816737","article-title":"Efficacy and Safety of Mesenchymal Stem Cells in Treatment of Complex Perianal Fistulas: A Meta-Analysis","volume":"2020","author":"Cheng","year":"2020","journal-title":"Stem Cells Int."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Aso, K., Tsuruhara, A., Takagaki, K., Oki, K., Ota, M., Nose, Y., Tanemura, H., Urushihata, N., Sasanuma, J., and Sano, M. (2016). Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148185"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/ibd\/izz288","article-title":"Preclinical Model of Perianal Fistulizing Crohn\u2019s Disease","volume":"26","author":"Flacs","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_141","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":"Herreros","year":"2009","journal-title":"Dis. Colon Rectum"},{"key":"ref_142","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":"ref_143","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1002\/stem.1357","article-title":"Autologous Adipose Tissue-Derived Stem Cells Treatment Demonstrated Favorable and Sustainable Therapeutic Effect for Crohn\u2019s Fistula","volume":"31","author":"Lee","year":"2013","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00384-012-1581-9","article-title":"Expanded Allogeneic Adipose-Derived Stem Cells (EASCs) for the Treatment of Complex Perianal Fistula in Crohn\u2019s Disease: Results from a Multicenter Phase I\/IIa Clinical Trial","volume":"28","author":"Alba","year":"2013","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_145","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\u2019s Fistula","volume":"4","author":"Cho","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1053\/j.gastro.2017.04.001","article-title":"Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for Treatment of Perianal Fistulas in Patients With Crohn\u2019s Disease","volume":"153","author":"Dietz","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1053\/j.gastro.2019.02.005","article-title":"Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Perianal Fistulas in Patients With Crohn\u2019s Disease","volume":"156","author":"Dige","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1053\/j.gastro.2019.01.032","article-title":"Long-Term Safety and Efficacy of Local Microinjection Combining Autologous Microfat and Adipose-Derived Stromal Vascular Fraction for the Treatment of Refractory Perianal Fistula in Crohn\u2019s Disease","volume":"156","author":"Serrero","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"6132340","DOI":"10.1155\/2019\/6132340","article-title":"Stem Cell Therapy: A Compassionate Use Program in Perianal Fistula","volume":"2019","author":"Herreros","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13287-020-01636-4","article-title":"Autologous Adipose-Derived Stem Cells for the Treatment of Crohn\u2019s Fistula-in-Ano: An Open-Label, Controlled Trial","volume":"11","author":"Zhou","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.3748\/wjg.v27.i24.3643","article-title":"Stem Cell Injection for Complex Anal Fistula in Crohn\u2019s Disease: A Single-Center Experience","volume":"27","author":"Schwandner","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1136\/gut.2007.128694","article-title":"Autologous Haematopoietic Stem Cell Transplantation without CD34+ Cell Selection in Refractory Crohn\u2019s Disease","volume":"57","author":"Cassinotti","year":"2008","journal-title":"Gut"},{"key":"ref_153","first-page":"1251","article-title":"Allogeneic Mesenchymal Stromal Cells for Refractory Luminal Crohn\u2019s Disease: A Phase I-II Study","volume":"50","author":"Gregoire","year":"2018","journal-title":"Dig. Liver Dis. Off. J. Ital. Soc. Gastroenterol. Ital. Assoc. Study Liver"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/MOG.0000000000000327","article-title":"Mesenchymal Stem\/Stromal Cell Therapy for Inflammatory Bowel Disease: An Updated Review with Maintenance of Remission","volume":"33","author":"Dave","year":"2017","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/sctm.19-0271","article-title":"Autologous Adipose-Derived Stem Cells for the Treatment of Complex Cryptoglandular Perianal Fistula: A Randomized Clinical Trial with Long-Term Follow-Up","volume":"9","author":"Herreros","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1097\/DCR.0000000000001333","article-title":"Early Results of a Phase I Trial Using an Adipose-Derived Mesenchymal Stem Cell-Coated Fistula Plug for the Treatment of Transsphincteric Cryptoglandular Fistulas","volume":"62","author":"Dozois","year":"2019","journal-title":"Dis. Colon Rectum"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.5966\/sctm.2015-0356","article-title":"Treatment of Crohn\u2019s-Related Rectovaginal Fistula With Allogeneic Expanded-Adipose Derived Stem Cells: A Phase I-IIa Clinical Trial","volume":"5","author":"Herreros","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/ibd\/izz215","article-title":"Matrix-Delivered Autologous Mesenchymal Stem Cell Therapy for Refractory Rectovaginal Crohn\u2019s Fistulas","volume":"26","author":"Lightner","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s10151-017-1684-y","article-title":"Anoperineal Lesions in Crohn\u2019s Disease: French Recommendations for Clinical Practice","volume":"21","author":"Bouchard","year":"2017","journal-title":"Tech. Coloproctol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/ecco-jcc\/jjw169","article-title":"3rd European Evidence-Based Consensus on the Diagnosis and Management of Crohn\u2019s Disease 2016: Part 2: Surgical Management and Special Situations","volume":"11","author":"Gionchetti","year":"2017","journal-title":"J. Crohns Colitis"},{"key":"ref_161","first-page":"212","article-title":"Enhancement of Wound Healing by Conditioned Medium of Adipose-Derived Stromal Cell with Photobiomodulation in Skin Wound","volume":"14","author":"Park","year":"2021","journal-title":"Int. J. Stem Cells"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"580131","DOI":"10.3389\/fcell.2020.580131","article-title":"Hypoxic Preconditioning Enhances Cellular Viability and Pro-Angiogenic Paracrine Activity: The Roles of VEGF-A and SDF-1a in Rat Adipose Stem Cells","volume":"8","author":"Zhao","year":"2020","journal-title":"Front. Cell Dev. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9967\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:02Z","timestamp":1760166002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":162,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189967"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189967","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,15]]}}}