Treatment effect of ex vivo expanded allogeneic bone marrow-derived mesenchymal stem cells for the treatment of fistulizing Crohn's disease are durable at 12 months.


Journal

Surgery
ISSN: 1532-7361
Titre abrégé: Surgery
Pays: United States
ID NLM: 0417347

Informations de publication

Date de publication:
Apr 2024
Historique:
received: 30 09 2023
revised: 02 11 2023
accepted: 07 11 2023
medline: 18 3 2024
pubmed: 15 12 2023
entrez: 14 12 2023
Statut: ppublish

Résumé

Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease. Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas. Bone marrow-derived mesenchymal stem cells (75 million in 7.5 mL) were injected at the time of exam under anesthesia on day 0 and month 3. Outcome measures were adverse events and combined clinical and pelvic magnetic resonance imaging healing at month 6 and month 12. Across all 3 trials, 64 patients were enrolled; 49 were treatment and 15 were control. At 6 months, combined clinical and radiographic healing was achieved in 83.3%, 33.3%, and 30.8% of the perianal, rectovaginal, and pouch fistula treatment cohorts, respectively. At 12 months, the treatment response was durable, with 67.7% of perianal, 37.5% of rectovaginal, and 46.2% of peripouch fistulas maintaining complete clinical and radiographic healing. Two patients in the perianal fistula control cohort achieved combined clinical and radiographic healing at 12 months, whereas 0% of rectovaginal and pouch control patients healed. Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal, rectovaginal, and peripouch fistulizing Crohn's disease. Treatment results are durable at 12 months.

Sections du résumé

BACKGROUND BACKGROUND
Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease.
METHODS METHODS
Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas. Bone marrow-derived mesenchymal stem cells (75 million in 7.5 mL) were injected at the time of exam under anesthesia on day 0 and month 3. Outcome measures were adverse events and combined clinical and pelvic magnetic resonance imaging healing at month 6 and month 12.
RESULTS RESULTS
Across all 3 trials, 64 patients were enrolled; 49 were treatment and 15 were control. At 6 months, combined clinical and radiographic healing was achieved in 83.3%, 33.3%, and 30.8% of the perianal, rectovaginal, and pouch fistula treatment cohorts, respectively. At 12 months, the treatment response was durable, with 67.7% of perianal, 37.5% of rectovaginal, and 46.2% of peripouch fistulas maintaining complete clinical and radiographic healing. Two patients in the perianal fistula control cohort achieved combined clinical and radiographic healing at 12 months, whereas 0% of rectovaginal and pouch control patients healed.
CONCLUSION CONCLUSIONS
Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal, rectovaginal, and peripouch fistulizing Crohn's disease. Treatment results are durable at 12 months.

Identifiants

pubmed: 38097485
pii: S0039-6060(23)00847-4
doi: 10.1016/j.surg.2023.11.007
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

984-990

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Auteurs

Amy L Lightner (AL)

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH. Electronic address: amylightner8@gmail.com.

Ana Otero Pineiro (AO)

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH.

Jane Reese (J)

National Center for Regenerative Medicine, Cleveland, OH.

Justin Ream (J)

Department of Abdominal Radiology, Digestive Disease Surgical Institute, Cleveland Clinic, OH.

Douglas Nachand (D)

Department of Abdominal Radiology, Digestive Disease Surgical Institute, Cleveland Clinic, OH.

Ashley C Adams (AC)

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH.

Neda Dadgar (N)

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH.

Tracy Hull (T)

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH.

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