Mesenchymal Stromal Cell Therapy Improves Refractory Perianal Fistula In Crohn’s Disease: Case Series Clinical Interventional Study
نویسندگان
1 Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
3 . Department of Hematology Oncology, Iran University of Medical Sciences, Tehran, Iran
4 Department of Reproductive Imaging, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
5 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
6 . Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
7 Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
8 Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
9 Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
10 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
11 Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
12 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
13 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
14 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
15 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
16 Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
17 Department of Stem Cells and Developmental Biology, Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
18 Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
doi
10.22074/cellj.2022.7981چکیده
Objective: Perianal fistulas in Crohn’s disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD.Materials and Methods: This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points.Results: In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn’s Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening.Conclusion: Local injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD.
