1. Efficacy of umbilical cord-derived mesenchymal stem cells and exosomes in conjunction with standard IBD drug on immune responses in an IBD mouse model.
- Author
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Kheradmand F, Yasaman Rahimzadeh SF, Esmaeili SA, Negah SS, Farkhad NK, Nazari SE, Hajinejad M, Khodadoust MA, Fadaee A, Afshari JT, and Khazaei M
- Subjects
- Animals, Mice, Humans, Dextran Sulfate, Interleukin-17 metabolism, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory immunology, Th17 Cells immunology, Th17 Cells metabolism, Th17 Cells drug effects, Interleukin-10 metabolism, Colon pathology, Colon drug effects, Colon metabolism, Spleen drug effects, Exosomes metabolism, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Disease Models, Animal, Umbilical Cord cytology, Inflammatory Bowel Diseases therapy, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases drug therapy, Mesenchymal Stem Cell Transplantation methods, Mice, Inbred C57BL, Mesalamine pharmacology, Mesalamine therapeutic use
- Abstract
Background: Inflammatory bowel disease (IBD) is a persistent inflammation of the digestive system, and Mesenchymal Stem Cells (MSCs) and their exosomes have demonstrated potential as treatments for this condition. The objective of this research was to examine the possible effectiveness of intraperitoneal injection of umbilical cord-MSCs (UC-MSCs) and their exosomes through a two-time injection regimen in a mouse model., Method: In this study, an animal model of a specific type of IBD in C57BL/6 mice, induced by dextran sulfate sodium (DSS), was utilized. The mice were treated with MSCs, exosomes, Mesalazine, and a combination of them. Upon sacrificing the mice, colon and spleen tissues were isolated to assess the changes in the mice's weight, colon length, spleen weight, and colitis' pathological symptoms. IL-10 and IL-17 levels were measured, and Treg and Th17 cell percentages were determined as well. Furthermore, colon tissue was stained to investigate histopathological changes., Results: In the groups that received MSCs, there was a significant reduction in the disease activity index and their combinations with exosomes and Mesalazine compared to the colitis group. Colon length increased in all groups except the exosome group. Histological measures were notably reduced in the MSC groups and their combinations. Significant increases in the IL-10 level of colon tissue and the proportion of Treg present in the spleen were observed in the groups receiving MSC and combination treatment. Furthermore, these groups showed a notable reduction in the percentage of spleen Th17 cells. However, IL17A decreased non-significantly in all groups., Conclusion: The results showed that intraperitoneal injection of UC-MSCs and their combination with exosome and Mesalazine in a murine colitis model improved the disease's symptoms. Therefore, MSCs and their combination with exosomes can be a promising therapeutic approach along with other common drugs for IBD, but exosomes alone could not significantly reduce the symptoms of colitis., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed following the Declaration of Helsinki Ethical Principles and approved by the Ethics Committee of the Mashhad University of Medical Sciences, Mashhad, Iran (IR. MUMS. RES.1401.133). (1) Title of the approved project: Evaluation of the effectiveness of umbilical cord mesenchymal stem cells along with the synergistic effect of the Exosomes derived from them on the immune response of an IBD mouse model. (2) Name of the institutional approval committee: the Ethics Committee of the Mashhad University of Medical Sciences, Mashhad, Iran. (3) Approval number: IR. MUMS. RES.1401.133. (4) Date of approval: 06/08/2022. After filling out the informed consent letter, human umbilical cords (H-UC) were obtained from Imam Reza hospital from full-term pregnancy mothers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2025
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