Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.
{"title":"Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.","authors":"Alireza Hadizadeh,Reza Akbari-Asbagh,Asieh Heirani-Tabasi,Masoud Soleimani,Parastou Gorovanchi,Nasser Ebrahimi Daryani,Amir Vahedi,Hengameh Nazari,Seyedeh-Parnian Banikarimi,Mahnoosh Abbaszade-Dibavar,Behnam Behboudi,Mohammad Sadegh Fazeli,Mohammad Reza Keramati,Amir Keshvari,Alireza Kazemeini,Haleh Pak,Amir-Reza Fazeli,Foroogh Alborzi,Seyed-Mohsen Ahmadi-Tafti","doi":"10.1097/dcr.0000000000003502","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nCrohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas.\r\n\r\nOBJECTIVE\r\nTo evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas.\r\n\r\nDESIGN\r\nNonrandomized, nonblinded single-center phase II clinical trial.\r\n\r\nSETTINGS\r\nTertiary university hospital.\r\n\r\nPATIENTS\r\nTwenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy.\r\n\r\nINTERVENTIONS\r\nAfter clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection.\r\n\r\nMAIN OUTCOME MEASURES\r\nThe primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts.\r\n\r\nRESULTS\r\nFistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results.\r\n\r\nCONCLUSIONS\r\nMSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.","PeriodicalId":11299,"journal":{"name":"Diseases of the Colon & Rectum","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diseases of the Colon & Rectum","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/dcr.0000000000003502","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
BACKGROUND
Crohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas.
OBJECTIVE
To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas.
DESIGN
Nonrandomized, nonblinded single-center phase II clinical trial.
SETTINGS
Tertiary university hospital.
PATIENTS
Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy.
INTERVENTIONS
After clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection.
MAIN OUTCOME MEASURES
The primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts.
RESULTS
Fistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results.
CONCLUSIONS
MSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.
期刊介绍:
Diseases of the Colon & Rectum (DCR) is the official journal of the American Society of Colon and Rectal Surgeons (ASCRS) dedicated to advancing the knowledge of intestinal disorders by providing a forum for communication amongst their members. The journal features timely editorials, original contributions and technical notes.