Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease

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Abstract

Objective: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. Patients and methods: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. Results: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p

Original languageEnglish
Pages (from-to)788-798
Number of pages11
JournalGut
Volume60
Issue number6
DOIs
Publication statusPublished - Jun 2011

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Mesenchymal Stromal Cells
Crohn Disease
Bone Marrow
Fistula
Therapeutics
Cutaneous Fistula
Injections
Regulatory T-Lymphocytes
Cell- and Tissue-Based Therapy
Outpatients
Stem Cells
Apoptosis
T-Lymphocytes
Safety
Recurrence

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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title = "Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease",
abstract = "Objective: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. Patients and methods: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. Results: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p",
author = "Rachele Ciccocioppo and Bernardo, {Maria Ester} and Adele Sgarella and Rita Maccario and Avanzini, {Maria Antonietta} and Cristina Ubezio and Antonella Minelli and Costanza Alvisi and Alessandro Vanoli and Fabrizio Calliada and Paolo Dionigi and Cesare Perotti and Franco Locatelli and Corazza, {Gino Roberto}",
year = "2011",
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T1 - Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease

AU - Ciccocioppo, Rachele

AU - Bernardo, Maria Ester

AU - Sgarella, Adele

AU - Maccario, Rita

AU - Avanzini, Maria Antonietta

AU - Ubezio, Cristina

AU - Minelli, Antonella

AU - Alvisi, Costanza

AU - Vanoli, Alessandro

AU - Calliada, Fabrizio

AU - Dionigi, Paolo

AU - Perotti, Cesare

AU - Locatelli, Franco

AU - Corazza, Gino Roberto

PY - 2011/6

Y1 - 2011/6

N2 - Objective: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. Patients and methods: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. Results: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p

AB - Objective: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. Patients and methods: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. Results: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p

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