Efficacy and safety of stem cell therapy for fistula management: An overview of existing systematic reviews

Tripti Tripathi; Syam Mohan; Hassan Ahmad Alfaifi; Abdullah Farasani; Roopashree R; Pawan Sharma; Abhishek Sharma; Apurva Koul; G V Siva Prasad; Sarvesh Rustagi; Jigisha Anand; Sanjit Sah; Shilpa Gaidhane; Ganesh Bushi; Diptismita Jena; Mahalaqua Nazli Khatib; Muhammed Shabil; Siddig Ibrahim Abdelwahab; Kiran Bhopte; Manvi Pant; Rachana Mehta; Sakshi Pandey; Manvinder Brar; Nagavalli Chilakam; Ashok Kumar Balaraman

doi:10.1097/JS9.0000000000002125

Efficacy and safety of stem cell therapy for fistula management: An overview of existing systematic reviews

Int J Surg. 2024 Oct 28;110(12):7573-7584. doi: 10.1097/JS9.0000000000002125. Online ahead of print.

Authors

Tripti Tripathi¹, Syam Mohan^{2

3}, Hassan Ahmad Alfaifi⁴, Abdullah Farasani⁵, Roopashree R⁶, Pawan Sharma⁷, Abhishek Sharma⁸, Apurva Koul⁹, G V Siva Prasad¹⁰, Sarvesh Rustagi¹¹, Jigisha Anand^{12

13}, Sanjit Sah^{14

15}, Shilpa Gaidhane¹⁶, Ganesh Bushi¹⁷, Diptismita Jena¹⁸, Mahalaqua Nazli Khatib¹⁹, Muhammed Shabil^{20

21}, Siddig Ibrahim Abdelwahab²², Kiran Bhopte²³, Manvi Pant²⁴, Rachana Mehta^{25

26}, Sakshi Pandey²⁷, Manvinder Brar²⁸, Nagavalli Chilakam²⁹, Ashok Kumar Balaraman³⁰

Affiliations

¹ Department of Physiology, Integral Institute of Medical Sciences and Research, Dashauli, Uttar Pradesh, India.
² Substance Abuse and Toxicology Research Centre, Jazan University, Jazan 45142, Saudi Arabia.
³ School of Health Sciences, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India.
⁴ Pharmaceutical Care Administration (Jeddah Second Health Cluster), Ministry of Health, Saudi Arabia.
⁵ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.
⁶ Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁷ Department of Sciences, Vivekananda Global University, Jaipur, Rajasthan-303012, India.
⁸ Department of Medicine, NIMS University, Jaipur, India.
⁹ Chandigarh Pharmacy College, Chandigarh Group of College, Jhanjeri, Mohali - 140307, Punjab, India.
¹⁰ Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh-531162, India.
¹¹ School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India.
¹² Department of Biotechnology, Graphic Era (Deemed to be University) Clement Town Dehradun, India.
¹³ Department of Allied Sciences, Graphic Era Hill University Clement Town Dehradun, India.
¹⁴ Department of Paediatrics, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune 411018, Maharashtra, India.
¹⁵ Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune 411018, Maharashtra, India.
¹⁶ One Health Centre, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India.
¹⁷ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
¹⁸ Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
¹⁹ Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India.
²⁰ University Center for Research and Development, Chandigarh University, Mohali, Punjab, India.
²¹ Medical Laboratories Techniques Department, AL-Mustaqbal University, 51001 Hillah, Babil, Iraq.
²² Medical Research Centre, Jazan University, Jazan 45142, Saudi Arabia.
²³ IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh 462044, India.
²⁴ New Delhi Institute of Management. New Delhi, India.
²⁵ Clinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana 121004, India.
²⁶ Dr Lal PathLabs - Nepal, Chandol-4, Maharajgunj, Kathmandu 44600, Nepal.
²⁷ Centre of Research Impact and Outcome, Chitkara University, Rajpura- 140417, Punjab, India.
²⁸ Chitkara Centre for Research and Development, Chitkara University, Himachal Pradesh-174103, India.
²⁹ Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India.
³⁰ Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000 Cyberjaya, Selangor, Malaysia.

Abstract

Background: Fistulas, abnormal connections between two anatomical structures, significantly impact the quality of life and can result from a variety of causes, including congenital defects, inflammatory conditions, and surgical complications. Stem cell therapy has emerged as a promising alternative due to its potential for regenerative and immunomodulatory effects. This overview of systematic reviews aimed to assess the safety and efficacy of stem cell therapy in managing fistulas, drawing on the evidence available.

Methods: This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to May 5th, 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3.

Results: Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192 to 1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036 to 2.116) and long-term (RR=1.422; 95% CI: 1.091 to 1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for general adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322 to 1.572).

Conclusion: Stem cell therapy shows promise as an effective and safe treatment for fistulas, particularly in inducing remission and promoting closure of complex fistulas. The findings advocate for further high-quality research to confirm these benefits and potentially incorporate stem cell therapy into standard clinical practice for fistula management. Future studies should focus on long-term outcomes and refining stem cell treatment protocols to optimize therapeutic efficacy.