Stem cell therapy for Crohn's disease: systematic review and meta-analysis of preclinical and clinical studies.

BACKGROUND: We explored whether stem cell therapy was effective for animal models and patients with Crohn's disease (CD). METHODS: We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality. RESULTS: We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD - 4.58, p = 0.000; rats: SMD - 1.41, P = 0.000) and lower myeloperoxidase levels (SMD - 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD - 2.10, P = 0.000), the CD endoscopic index of severity (SMD - 3.40, P = 0.000) and simplified endoscopy score for CD (SMD - 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3-24 months after transplantation. CONCLUSIONS: Stem cell transplantation is a valuable supplementary therapy for CD.

Mesenchymal stem cells for the treatment of ulcerative colitis: a systematic review and meta-analysis of experimental and clinical studies.

OBJECTIVE: To explore the promising use of mesenchymal stem cells (MSCs) for ulcerative colitis (UC). METHODS: Studies reporting MSC treatment on UC were searched on five databases. Methodological quality was assessed based on the SYRCLE's Risk of Bias (RoB) tool and MINORS tool. Data analysis was conducted using Engauge Digitizer 10.8 and Stata 14.0. RESULTS: A total of 15 studies met the inclusion criteria including 8 animal (n = 132) and 7 human (n = 216) trials. In animal studies, mice treated with MSCs had significantly lower disease activity index (DAI) than that in the control group: the 1st day (standardized mean difference (SMD) - 0.753, p = 0.027), the 3rd day (SMD - 1.634, p = 0.000), the 5th day (SMD - 2.124, p = 0.000), the 7th day (SMD - 5.327, p = 0.000), the 9th day (SMD - 2.979, p = 0.000), and the 14th day (SMD - 5.032, p = 0.000). Lower histopathological score (HS) (SMD - 5.15, p < 0.05) and longer colon length (SMD 2.147, p = 0.001) in mice treated with MSCs were also indicated. The main outcome in clinical trials showed, compared with control group, healing rate of patients accompanied by MSC therapy elevated obviously: MSCs vs 5-aminosalicylic acids (5-ASA) (RR = 2.317, p = 0.000) and MSCs + 5-ASA vs placebo + 5-ASA (RR = 5.118). The analytical data in 4 trials conducted with single-arm studies also demonstrated increased healing rate (0.787) after MSC treatment (p = 0.000). CONCLUSION: Our meta-analysis results supported that MSCs could be an underlying method of treating UC.