Rachele Ciccocioppo1, Alessandra Gallia2, Adele Sgarella3, Peter Kruzliak4, Paolo G Gobbi2, Gino Roberto Corazza2. 1. 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. 2. 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. 3. Clinica Chirurgica, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy. 4. International Clinical Research Center, St Anne's University Hospital and Masaryk University, Pekarska Brno, Czech Republic.
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. PATIENTS AND 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. CONCLUSION: Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.
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. PATIENTS AND 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. CONCLUSION: Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.
Authors: G Pellino; D S Keller; G M Sampietro; I Angriman; M Carvello; V Celentano; F Colombo; F Di Candido; S Laureti; G Luglio; G Poggioli; M Rottoli; S Scaringi; G Sciaudone; G Sica; L Sofo; S Leone; S Danese; A Spinelli; G Delaini; F Selvaggi Journal: Tech Coloproctol Date: 2020-03-14 Impact factor: 3.781
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Authors: Rachele Ciccocioppo; Claudia C Dos Santos; Daniel C Baumgart; Giuseppina C Cangemi; Vincenzo Cardinale; Carolina Ciacci; Paolo De Coppi; Debashis Haldar; Catherine Klersy; M Cristina Nostro; Michael Ott; Lorenzo Piemonti; Alice A Tomei; Basak Uygun; Stefania Vetrano; Giuseppe Orlando Journal: Cytotherapy Date: 2018-02-15 Impact factor: 5.414
Authors: Abhinav Vasudevan; David H Bruining; Edward V Loftus; William Faubion; Eric C Ehman; Laura Raffals Journal: World J Gastroenterol Date: 2021-07-07 Impact factor: 5.742