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Gastroenterology. 2015 Oct;149(4):918-27.e6. doi: 10.1053/j.gastro.2015.06.014. Epub 2015 Jun 25.

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease.

Author information

1
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
2
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
3
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
4
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
5
Department Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
6
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
7
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; The Jon J van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University Medical Center, Leiden, The Netherlands.
8
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: ae.meulen@lumc.nl.
9
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California.

Abstract

BACKGROUND & AIMS:

Patients with perianal fistulizing Crohn's disease have a poor prognosis because these lesions do not heal well. We evaluated the effects of local administration of bone marrow-derived mesenchymal stromal cells (MSCs) to these patients from healthy donors in a double-blind, placebo-controlled study.

METHODS:

Twenty-one patients with refractory perianal fistulizing Crohn's disease were randomly assigned to groups given injections of 1 × 10(7) (n = 5, group 1), 3 × 10(7) (n = 5, group 2), or 9 × 10(7) (n = 5, group 3) MSCs, or placebo (solution with no cells, n = 6), into the wall of curettaged fistula, around the trimmed and closed internal opening. The primary outcome, fistula healing, was determined by physical examination 6, 12, and 24 weeks later; healing was defined as absence of discharge and <2 cm of fluid collection-the latter determined by magnetic resonance imaging at week 12. All procedures were performed at Leiden University Medical Center, The Netherlands, from June 2012 through July 2014.

RESULTS:

No adverse events were associated with local injection of any dose of MSCs. Healing at week 6 was observed in 3 patients in group 1 (60.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 1 patient in the placebo group (16.7%) (P = .08 for group 2 vs placebo). At week 12, healing was observed in 2 patients in group 1 (40.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 2 patients in the placebo group (33.3%); these effects were maintained until week 24 and even increased to 4 (80.0%) in group 1. At week six, 4 of 9 individual fistulas had healed in group 1 (44.4%), 6 of 7 had healed in group 2 (85.7%), and 2 of 7 had healed in group 3 (28.6%) vs 2 of 9 (22.2%) in the placebo group (P = .04 for group 2 vs placebo). At week twelve, 3 of 9 individual fistulas had healed in group 1 (33.3%), 6 of 7 had healed in group 2 (85.7%), 2 of 7 had healed in group 3 (28.6%), and 3 of 9 had healed in the placebo group (33.3%). These effects were stable through week 24 and even increased to 6 of 9 (66.7%) in group 1 (P = .06 group 2 vs placebo, weeks 12 and 24).

CONCLUSIONS:

Local administration of allogeneic MSCs was not associated with severe adverse events in patients with perianal fistulizing Crohn's disease. Injection of 3 × 10(7) MSCs appeared to promote healing of perianal fistulas. ClinicalTrials.gov ID NCT01144962.

KEYWORDS:

Cell Therapy; Inflammatory Bowel Disease; Perianal Fistulas; Treatment

PMID:
26116801
DOI:
10.1053/j.gastro.2015.06.014
[Indexed for MEDLINE]

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