Bhatnagar P, Elhariri S, Burud IAS, Eid N. Stem cell- and extracellular vesicle-based therapies for perianal fistulizing Crohn’s disease: An updated review. World J Gastroenterol 2025; 31(39): 112229 [DOI: 10.3748/wjg.v31.i39.112229]
Corresponding Author of This Article
Nabil Eid, MD, PhD, Associate Professor, Department of Human Biology, Anatomy Division, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
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. Oct 21, 2025; 31(39): 112229 Published online Oct 21, 2025. doi: 10.3748/wjg.v31.i39.112229
Stem cell- and extracellular vesicle-based therapies for perianal fistulizing Crohn’s disease: An updated review
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, School of Medicine, Clinical Campus, IMU University, Seremban 70300, Negeri Sembilan, Malaysia
Nabil Eid, Department of Human Biology, Anatomy Division, School of Medicine, IMU University, Kuala Lumpur 57000, Malaysia
Author contributions: Bhatnagar P wrote the manuscript; Elhariri S and Burud IAS revised and edited the manuscript; Eid N wrote, edited, and approved the final draft of the manuscript; All authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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, MD, PhD, Associate Professor, Department of Human Biology, Anatomy Division, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Received: July 22, 2025 Revised: August 3, 2025 Accepted: September 15, 2025 Published online: October 21, 2025 Processing time: 92 Days and 2.8 Hours
Abstract
Perianal fistulizing Crohn’s disease (PFCD) is a complication of CD that significantly impacts patients’ quality of life, particularly their social and sexual well-being. Despite advances in therapy, its treatment remains a major challenge in the field of inflammatory bowel disease. The pathogenesis of PFCD involves increased production of inflammatory cytokines by infiltrating macrophages and lymphocytes, stimulation of the epithelial-to-mesenchymal transition, activation of myofibroblasts, and elevated levels of matrix metalloproteinases. Mesenchymal stem cells (MSCs) are multipotent stromal cells with self-renewal and differentiation capabilities. Evidence from animal models and clinical trials indicates that MSC injection into PFCD lesions suppresses the infiltration of inflammatory cells and cytokines, resulting in complete fistula healing. More recently, MSC-derived extracellular vesicles (EVs) have shown promising results in promoting fistula healing, particularly in cases of refractory or relapsing fistulas. Notably, the activation of macroautophagy (hereafter referred to as autophagy) in MSCs has been shown to accelerate the healing process. This narrative review discusses the mechanisms underlying PFCD pathogenesis, the therapeutic roles of MSCs and their EVs, and the potential role of autophagy upregulation in enhancing MSC function and EV production.
Core Tip: Perianal fistulizing Crohn’s disease (PFCD) is a severe complication of CD, characterized by the accumulation of inflammatory cells and elevated cytokine production. Although various medical and surgical approaches aim to control this disease, recurrence remains a major challenge. Both animal models and clinical trials have shown that mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) can reduce inflammation and promote healing in refractory PFCD effects that may be further enhanced by autophagy activation. This review highlights the therapeutic potential of MSCs and their EVs in PFCD treatment and explores the supportive role of autophagy in enhancing their efficacy.
