title: Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells.
abstract: OBJECTIVE
  To assess the long-term outcome of patients treated with serial intrafistular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) for refractory Crohn fistulas in terms of safety and efficacy.
  
  
  METHODS
  Starting from January 10, 2007, through June 30, 2014, clinical evaluation, calculation of the Crohn disease activity index (CDAI), therapeutic management, and documentation of adverse events in 8 of the 10 patients (5 men; median age, 37 years) who had been injected locally with MSCs were prospectively recorded for 72 months. Cumulative probabilities of fistula recurrence and medical or surgical treatment were estimated using a Kaplan-Meier method, whereas differences among the pre- and post-MSC CDAI values were calculated with the Mann-Whitney U test.
  
  
  RESULTS
  Following disease remission observed after 12 months from MSC treatment (P<.001), the mean CDAI score increased significantly during the subsequent 2 years (P=.007), and was then followed by a gradual decrease, with the patients achieving remission again (P=.02) at the end of the 5-year follow-up. The probability of fistula relapse-free survival was 88% at 1 year, 50% at 2 years, and 37% during the following 4 years, and the cumulative probabilities of surgery- and medical-free survival were 100% and 88% at 1 year, 75% and 25% at 2, 3, and 4 years, and 63% and 25% at 5 and 6 years, respectively. No adverse events were recorded.
  
  
  CONCLUSIONS
  Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.
authors.affiliation: Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy. Electronic address: rachele.ciccocioppo@unipv.it.
authors.forename: Rachele
authors.initials: R
authors.lastname: Ciccocioppo
authors.affiliation: Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gallia
authors.affiliation: Clinica Chirurgica, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Sgarella
authors.affiliation: International Clinical Research Center, St Anne's University Hospital and Masaryk University, Pekarska Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy.
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Gobbi
authors.affiliation: Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy.
authors.forename: Gino Roberto
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000150:complications* / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007412:Intestinal Fistula / Q000209:etiology* / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult