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.
Dis Colon Rectum
; 2024 Sep 06.
Article
en En
| MEDLINE
| ID: mdl-39250316
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 OUTCOMEMEASURES:
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Dis Colon Rectum
Año:
2024
Tipo del documento:
Article
País de afiliación:
Irán
Pais de publicación:
Estados Unidos