Bhatnagar P, Elhariri S, Burud IAS, Eid N. Perianal fistulizing Crohn’s disease: Mechanisms and treatment options focusing on cellular therapy. World J Gastroenterol 2025; 31(9): 100221 [DOI: 10.3748/wjg.v31.i9.100221]
Corresponding Author of This Article
Nabil Eid, Associate Professor, Academic Editor, Senior Lecturer, MD, PhD, Department of Anatomy, Division of Human Biology, School of Medicine, IMU University, No. 126 Jalan Jalil Perkasa 19, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Mar 7, 2025; 31(9): 100221 Published online Mar 7, 2025. doi: 10.3748/wjg.v31.i9.100221
Perianal fistulizing Crohn’s disease: Mechanisms and treatment options focusing on cellular therapy
Payal Bhatnagar, Sherreen Elhariri, Ismail A S Burud, Nabil Eid
Payal Bhatnagar, Department of Pharmaceutical Technology, School of Pharmacy, IMU University, Kuala Lumpur 57000, Malaysia
Sherreen Elhariri, Ismail A S Burud, Department of Surgery, IMU University, Clinical Campus, Seremban 70300, Negeri Sembilan, Malaysia
Nabil Eid, Department of Anatomy, Division of Human Biology, School of Medicine, IMU University, Kuala Lumpur 57000, Malaysia
Author contributions: Bhatnagar P designed the figure; Burud IAS revised the manuscript; Bhatnagar P, Elhariri S, and Eid N wrote the manuscript; Eid N approved the final draft; and all authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nabil Eid, Associate Professor, Academic Editor, Senior Lecturer, MD, PhD, Department of Anatomy, Division of Human Biology, School of Medicine, IMU University, No. 126 Jalan Jalil Perkasa 19, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Received: August 10, 2024 Revised: January 6, 2025 Accepted: January 21, 2025 Published online: March 7, 2025 Processing time: 192 Days and 2.9 Hours
Abstract
Perianal fistulizing Crohn’s disease (PFCD) is a common presentation of CD, which affects the patients’ quality of life, including social and sexual function. The management of PFCD remains a critical challenge in inflammatory bowel disease, primarily due to limited understanding of the mechanisms involved in its pathogenesis, complicating medical treatment. Increased production of inflammatory cytokines such as tumor necrosis factor and interleukin-13 by infiltrating macrophages and other inflammatory cells stimulate the epithelial-to-mesenchymal transition, resulting in activation of myofibroblasts and elevation of matrix metalloproteinases, leading to fistula formation. Given the potential for malignant transformation, PFCD screening is critical. Cytokine and inflammation-targeted therapies can help control this disease, but recurrence is a common complication. Surgical interventions such as fistulotomy represent viable therapeutic options, with magnetic resonance imaging serving as an important diagnostic tool for delineating fistula tract anatomy. Animal models and clinical trials demonstrate that injection of mesenchymal stem cells (MSCs) into the fistula results in suppression of the inflammatory cells and cytokines and complete resolution of PFCD. Recently, MSC-derived extracellular vesicles were found to stimulate fistula healing, with encouraging results. In this article, we comment on the review article by Pacheco et al, summarizing the various lines of PFCD treatment and highlighting the role of screening for this disease. Importantly, we focus on the various mechanisms involved in the pathogenesis of PFCD, the therapeutic roles of MSCs and related extracellular vesicles, and explore the potential role of autophagy in enhancing the therapeutic efficacy of these cells, which may help in the treatment of this disease.
Core Tip: Perianal fistulizing Crohn’s disease (PFCD) is a common complication of CD, characterized by complex pathogenic mechanisms involving inflammatory cell accumulation, particularly macrophages, and enhanced cytokine production. These processes drive epithelial-to-mesenchymal transition, myofibroblast activation, upregulation of matrix metalloproteinases, ultimately leading to fistula formation. While various medical and surgical options target inflammatory processes in this disease, recurrence remains a substantial challenge. Local administration of mesenchymal stem cells or their derived extracellular vesicles has emerged as a promising therapeutic strategy through suppression of the inflammatory cells and promotion of fistula healing in PFCD. Here we summarize the various mechanisms involved in PFCD pathogenesis, with particular emphasis on mesenchymal stem cell therapy and their derived extracellular vesicles.
