Safety and efficacy of stem cell therapy for Crohn's disease: An umbrella review of systematic reviews

Lakshmi Thangavelu; Syam Mohan; Hassan Ahmad Alfaifi; Abdullah Farasani; Soumya V Menon; Pooja Bansal; Chhavi Choudhary; M Ravi Kumar; Raghav Vashishth; Afrah Majeed Ahmed Al-Rihaymee; Sarvesh Rustagi; Anil K Malhotra; Muhammed Shabil; Mahalaqua Nazli Khatib; Quazi Syed Zahiruddin; Siddig Ibrahim Abdelwahab; Ganesh Bushi; Saleh Hussain A Almasabi; Hayam A Alrasheed; Ali A Rabaan

doi:10.1097/JS9.0000000000002104

Safety and efficacy of stem cell therapy for Crohn's disease: An umbrella review of systematic reviews

Int J Surg. 2024 Oct 1;110(12):7495-7507. doi: 10.1097/JS9.0000000000002104. Online ahead of print.

Authors

Lakshmi Thangavelu¹, Syam Mohan^{2

3}, Hassan Ahmad Alfaifi⁴, Abdullah Farasani⁵, Soumya V Menon⁶, Pooja Bansal⁷, Chhavi Choudhary⁸, M Ravi Kumar⁹, Raghav Vashishth¹⁰, Afrah Majeed Ahmed Al-Rihaymee¹¹, Sarvesh Rustagi¹², Anil K Malhotra¹³, Muhammed Shabil¹⁴, Mahalaqua Nazli Khatib¹⁵, Quazi Syed Zahiruddin¹⁶, Siddig Ibrahim Abdelwahab¹⁷, Ganesh Bushi^{18

19}, Saleh Hussain A Almasabi²⁰, Hayam A Alrasheed²¹, Ali A Rabaan^{22

23

24}

Affiliations

¹ Center for Global health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, 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 Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan-303012, India.
⁸ Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjeri, Mohali 140307, Punjab, India.
⁹ Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh-531162, India.
¹⁰ Department of Surgery, NIMS University, Jaipur, India.
¹¹ Anesthesia Techniques Department, College of Health and Medical Techniques, Al-Mustaqbal University, 51001, Babylon, Iraq.
¹² School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India.
¹³ Department of General Surgery, Graphic Era (Deemed to be University) Clement Town Dehradun, India.
¹⁴ University Center for Research and Development, Chandigarh University, Mohali, Punjab, India.
¹⁵ Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India.
¹⁶ South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India.
¹⁷ Medical Research Centre, Jazan University, Jazan 45142, Saudi Arabia.
¹⁸ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
¹⁹ Evidence for Policy and Learning, Global Center for Evidence Synthesis, Chandigarh, India.
²⁰ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia.
²¹ Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
²² Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
²³ College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
²⁴ Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan.

Abstract

Background: Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease.

Methods: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to April 20, 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates.

Results: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192 to 1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13 to 1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036 to 2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091 to 1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193 to 6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events.

Conclusion: Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition.