间充质干细胞治疗克罗恩病肛瘘的研究进展
Research Progress of Mesenchymal Stem Cells for Anal Fistula in Crohn’s Disease
DOI: 10.12677/acm.2025.15123597, PDF,    科研立项经费支持
作者: 耿 俊, 陈 昊, 严跃华, 易嘉钦, 刘晓玉:南京中医药大学第一临床医学院,江苏 南京;贡钰霞, 王 浩*:南京中医药大学附属医院肛肠科,江苏 南京
关键词: 克罗恩病肛瘘间充质干细胞研究进展Crohn’s Disease Perianal Fistulizing Mesenchymal Stem Cells Research Progress
摘要: 克罗恩病(Crohn’s disease, CD)是一种慢性炎症性肠道疾病,肛瘘是其常见的严重并发症。间充质干细胞(Mesenchymal stem cells, MSCs)因其具备免疫调节、组织修复和抗纤维化作用,能促进病灶的修复和再生,被认为具有治疗克罗恩病肛瘘(Perianal fistulizing Crohn’s disease, PFCD)的潜力。本文旨在概述间充质干细胞的基本特性、治疗机制以及其在临床研究中的进展。
Abstract: Crohn’s disease is a chronic inflammatory bowel disease, and perianal fistulizing is a common and serious complication. Mesenchymal stem cells (Mesenchymal stem cells, MSCs) are considered to have the potential to treat PFCD because of their immunomodulation, tissue repair and antifibrotic effects, which can promote the repair and regeneration of lesions. This article aims to summary the basic characteristics, therapeutic mechanisms, and clinical research progress of mesenchymal stem cells.
文章引用:耿俊, 陈昊, 贡钰霞, 严跃华, 易嘉钦, 刘晓玉, 王浩. 间充质干细胞治疗克罗恩病肛瘘的研究进展[J]. 临床医学进展, 2025, 15(12): 1815-1822. https://doi.org/10.12677/acm.2025.15123597

参考文献

[1] Muresan, S. and Slevin, M. (2024) C-Reactive Protein: An Inflammatory Biomarker and a Predictor of Neurodegenerative Disease in Patients with Inflammatory Bowel Disease? Cureus, 16, e59009. [Google Scholar] [CrossRef] [PubMed]
[2] Niu, Y., Zhang, J., Shi, D., Zang, W. and Niu, J. (2023) Glycosides as Potential Medicinal Components for Ulcerative Colitis: A Review. Molecules, 28, Article No. 5210. [Google Scholar] [CrossRef] [PubMed]
[3] Bougie, O., Randle, E., Thurston, J., Magee, B., Warshafsky, C. and Rittenberg, D. (2024) Guideline No. 447: Diagnosis and Management of Endometrial Polyps. Journal of Obstetrics and Gynaecology Canada, 46, Article ID: 102402. [Google Scholar] [CrossRef] [PubMed]
[4] Wang, Z., Huang, M., Zhang, Y., Jiang, X. and Xu, L. (2023) Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm. Stem Cells International, 2023, Article ID: 4547875. [Google Scholar] [CrossRef] [PubMed]
[5] Aru, B., Akdeniz, T., Dağdeviren, H., Gürel, G. and Yanıkkaya Demirel, G. (2023) Testosterone Propionate Promotes Proliferation and Viability of Bone Marrow Mesenchymal Stem Cells While Preserving Their Characteristics and Inducing Their Anti-Cancer Efficacy. Balkan Medical Journal, 40, 117-123. [Google Scholar] [CrossRef] [PubMed]
[6] He, Y., Tang, Y., Zeng, B., Chen, X., Yuan, L., Lu, Y., et al. (2024) Black Phosphorus Quantum Dot-Modified ADSCs as a Novel Therapeutic for Periodontitis Bone Loss Coupling of Osteogenesis and Osteoimmunomodulation. Materials Today Bio, 27, Article ID: 101122. [Google Scholar] [CrossRef] [PubMed]
[7] Iribar, H., Pérez-López, V., Etxaniz, U., Gutiérrez-Rivera, A. and Izeta, A. (2017) Schwann Cells in the Ventral Dermis Do Not Derive from Myf5-Expressing Precursors. Stem Cell Reports, 9, 1477-1487. [Google Scholar] [CrossRef] [PubMed]
[8] Zhang, Y., Zhao, F., Li, J., Yuan, B., Zhu, X., Zhang, K., et al. (2024) A Bioswitchable Antibacterial Strategy for the Treatment of Implant-Associated Infections. Chemical Engineering Journal, 492, Article ID: 152402. [Google Scholar] [CrossRef
[9] Yuan, S., Chen, Q., Guo, M., Xu, Y., Wang, W. and Li, Z. (2024) Fabrication of Bioresorbable Barrier Membranes from Gelatin/Poly(4‐Hydroxybutyrate) (P4HB). Macromolecular Bioscience, 24, Article ID: 2400036. [Google Scholar] [CrossRef] [PubMed]
[10] Sadr, S., Lotfalizadeh, N., Ghaniei, A., Ahmadi Simab, P. and Hajjafari, A. (2023) An Update on Characterisation and Applications of Mesenchymal Stem Cells from Chickens with Challenges and Prospective Review. Worlds Poultry Science Journal, 80, 589-610. [Google Scholar] [CrossRef
[11] Mendiratta, M., Mendiratta, M., Sahoo, R., et al. (2024) Harnessing Apoptotic Mesenchymal Stem Cell-Derived Small Extracellular Vesicles as a Next Generation Therapeutic Modality for Immunomodulation. Cytotherapy, 26, S81-S82.
[12] Scharl, M., et al. (2022) Pathogenesis of Crohn’s Disease-Associated Fistulae. PMC.
[13] Kawecki, M.P., Kruk, A.M., Drążyk, M., Domagała, Z. and Woźniak, S. (2025) Exploring Perianal Fistulas: Insights into Biochemical, Genetic, and Epigenetic Influences—A Comprehensive Review. Gastroenterology Insights, 16, Article No. 10. [Google Scholar] [CrossRef
[14] McGregor, C.G.C., Tandon, R. and Simmons, A. (2023) Pathogenesis of Fistulating Crohn’s Disease: A Review. Cellular and Molecular Gastroenterology and Hepatology, 15, 1-11. [Google Scholar] [CrossRef] [PubMed]
[15] Altaie, A., Simone, D., McDermott, N., Owston, H., Attar, M., Jin, L., et al. (2025) Healthy Human Enthesis Stromal Cells Mediate Immunoregulation via the CD39/CD73 Adenosine Ectonucleotidase Pathway. Annals of the Rheumatic Diseases. [Google Scholar] [CrossRef
[16] Panés, J., et al. (2018) Long-Term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients with Crohn’s Disease. Gastroenterology, 154, 1334-1342.e4.
[17] McGregor, C., Qin, X., Jagielowicz, M., Gupta, T., Yin, Z., Lentsch, V., et al. (2025) Spatial Fibroblast Niches Define Crohn’s Fistulae. Nature. [Google Scholar] [CrossRef
[18] Ossium Health, Inc. (2022) Mesenchymal Stem Cells for Anal Fistulas (OSSM-001).
[19] Liu, Q., Chen, S. and Xu, H. (2024) Comparative Analysis of Mesenchymal Stem Cells from Different Sources in the Treatment of Perianal Fistulizing Crohn’s Disease. Inflammatory Bowel Diseases, 30, 110-120.
[20] Zhang, Z., Huang, Z. and Wang, Y. (2023) Mesenchymal Stem Cells in the Treatment of Perianal Fistulizing Crohn’s Disease: A Comprehensive Review. Journal of Crohns and Colitis, 17, 15-25.
[21] Wang, X., Li, Y. and Zhang, J. (2024) Optimizing the Expansion and Therapeutic Potential of Mesenchymal Stem Cells. Stem Cell Research & Therapy, 15, 75-88.
[22] Anosov, I.S., Eryshova, T.A., Khryukin, R.Yu., Zakharov, M.A. and Achkasov, S.I. (2024) Mesenchymal Stem Cells for Perianal Fistulizing Crohn’s Disease (Systematic Review and Meta-Analysis). Koloproktologia, No. 3, 100-111.
[23] Chen, L., Zhang, H. and Li, X. (2024) Long-Term Outcomes of Mesenchymal Stem Cell Therapy for Perianal Fistulizing Crohn’s Disease. Journal of Clinical Medicine, 13, 523-533.
[24] Sun, W., Wang, J. and Zhao, Y. (2023) Monitoring Adverse Effects and Improving the Safety Profile of Mesenchymal Stem Cell Therapy in Inflammatory Bowel Diseases. Translational Research, 245, 101-115.
[25] Zhang, Y., Liu, Z. and Wang, X. (2023) Mesenchymal Stem Cell-Derived Extracellular Vesicles: Potential Therapeutics for Crohn’s Disease. Journal of Cellular Physiology, 238, 678-690.
[26] Ou, Y., Wang, S. and Zhao, F. (2024) The Role of Mesenchymal Stem Cells in Immune Regulation and Treatment of Inflammatory Bowel Disease. Immunology Letters, 251, 20-28.
[27] Lee, J., Kim, H. and Park, Y. (2024) Mesenchymal Stem Cell Therapy for Inflammatory Bowel Disease: Current Status and Future Perspectives. Stem Cell Reviews and Reports, 20, 45-62.
[28] Huang, Y., Chen, Y. and Zhang, H. (2023) Genetic Modification of Mesenchymal Stem Cells for Enhanced Therapeutic Efficacy in Crohn’s Disease. Molecular Therapy, 31, 507-517.
[29] Li, J., Sun, H. and Zhang, Z. (2023) Combined Application of Mesenchymal Stem Cells and Biologics for the Treatment of Refractory Crohn’s Disease. International Journal of Molecular Sciences, 24, 150-163.
[30] Xu, J., Wang, R. and Liu, L. (2024) New Insights into the Synergistic Effects of Mesenchymal Stem Cells and Traditional Drugs in Crohn’s Disease Treatment. Journal of Clinical Investigation, 134, e154320.
[31] Park, Y., Kim, S. and Lee, J. (2024) Comparative Study of Mesenchymal Stem Cells from Different Tissues for the Treatment of Crohn’s Disease. Journal of Stem Cell Research & Therapy, 18, 97-107.
[32] Li, W., Zhang, J. and Huang, Z. (2024) Clinical Trials and Future Directions for Mesenchymal Stem Cell Therapy in Crohn’s Disease. Journal of Gastroenterology and Hepatology, 39, 110-120.
[33] Zhao, Y., Xu, L. and Wang, J. (2023) Exosome-Based Therapies for Inflammatory Bowel Disease: Current Status and Future Perspectives. Journal of Clinical Medicine, 12, 1340.
[34] Sun, L., Zhao, Y. and Li, P. (2024) The Potential of Mesenchymal Stem Cells in the Treatment of Crohn’s Disease: From Bench to Bedside. Frontiers in Immunology, 15, 423-435.
[35] Zhou, W., Li, M. and Zhang, H. (2023) Advances in Mesenchymal Stem Cell Therapy for Crohn’s Disease. Stem Cell Research, 30, 101-115.
[36] Zhao, H., Wang, L. and Zhang, X. (2024) The Role of Mesenchymal Stem Cells in Immune Modulation and Tissue Repair in Crohn’s Disease. Inflammatory Bowel Diseases, 30, 215-227.
[37] Kim, J., Lee, S. and Park, Y. (2023) Enhancing Mesenchymal Stem Cell Therapy for Crohn’s Disease through Gene Editing. Journal of Gene Medicine, 25, 45-58.
[38] Liu, H., Zhang, Y. and Wang, L. (2023) Assessing the Safety Profile of Mesenchymal Stem Cell Therapy in Treating Crohn’s disease: A multi-center study. Journal of Clinical Gastroenterology, 21(3), 320-334.
[39] Guo, Q., Sun, L. and Zhao, H. (2024) Evaluating the immunomodulatory effects of mesenchymal stem cell-derived exo-Somes in Crohn’s Disease. Journal of Cellular Therapy, 16, 110-122.
[40] Wu, Z., Zhang, L. and Li, P. (2023) Investigating the Therapeutic Potential of Mesenchymal Stem Cells in Treating Refractory Crohn’s Disease. Journal of Experimental Medicine, 30, 210-222.
[41] Zhao, H., Sun, L. and Guo, Y. (2024) The Role of Mesenchymal Stem Cells in Modulating the Immune Response in Crohn’s Disease. Journal of Clinical Immunology, 23, 300-312.
[42] Liu, M., Zhang, T. and Sun, J. (2023) Safety and Tolerability of Mesenchymal Stem Cell Therapy in Patients with Crohn’s Disease: A Long-Term Follow-Up Study. Journal of Clinical Trials, 15, 450-462.
[43] Wu, X., Chen, S. and Zhang, R. (2024) The Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Treating Perianal Fistulizing Crohn’s Disease. Journal of Exosome Research, 7, 210-220.
[44] Huang, R., Wang, X. and Liu, J. (2023) Evaluating the Long-Term Safety and Efficacy of Mesenchymal Stem Cell Therapy in Crohn’s Disease. Clinical Trials in Gastroenterology, 12, 345-356.
[45] Zhao, X., Sun, L. and Guo, Y. (2024) Comparative Analysis of Adipose-Derived versus Bone Marrow-Derived Mesenchymal Stem Cells in Treating Crohn’s Disease. Stem Cells Translational Medicine, 13, 502-514.
[46] Lee, Y., Zhang, W. and Wang, L. (2023) Exploring the Potential of Combining Mesenchymal Stem Cells with Biologics in Crohn’s Disease Therapy. BioMed Research International, 11, 567-580.
[47] Li, T., Zhao, H. and Liu, M. (2024) Monitoring the Safety Profile of Mesenchymal Stem Cell Therapy in Crohn’s Disease: A Comprehensive Review. Journal of Clinical Monitoring, 9, 145-158.
[48] Sun, Y., Zhang, Q. and Li, Z. (2023) Investigating the Immunomodulatory Effects of Mesenchymal Stem Cells in Crohn’s Disease Models. Immunotherapy Journal, 17, 715-728.
[49] Guo, F., Wang, J. and Chen, H. (2024) Optimizing the Therapeutic Potential of Mesenchymal Stem Cells in Crohn’s Disease Using Gene Editing. Journal of Stem Cell Research, 9, 801-813.
[50] Liu, P., Zhao, K. and Zhang, Y. (2023) Combining Mesenchymal Stem Cells with Anti-Inflammatory Agents in Crohn’s Disease Treatment. Journal of Gastroenterology and Hepatology Research, 25, 200-212.
[51] Zhao, H., Guo, Y. and Wang, X. (2024) Mesenchymal Stem Cell-Derived Exosomes as a Novel Therapy for Crohn’s Disease: An Updated Review. Stem Cell Research and Therapy, 15, 550-562.
[52] Sun, F., Liu, Q. and Wang, S. (2023) Exploring the Therapeutic Potential of Genetically Modified Mesenchymal Stem Cells in Crohn’s Disease. Journal of Molecular Medicine, 21, 560-572.
[53] Li, J., Zhang, T. and Liu, W. (2024) Clinical Outcomes of Mesenchymal Stem Cell Therapy in Crohn’s Disease: A Multi-center Trial. International Journal of Clinical Trials, 10, 345-357.
[54] Guo, H., Sun, L. and Zhao, Q. (2023) Evaluating the Immunosuppressive Properties of Mesenchymal Stem Cells in Inflammatory Bowel Disease Models. Cellular Immunology Journal, 22, 450-462.
[55] Wu, L., Wang, P. and Li, M. (2024) The Potential of Adipose-Derived Mesenchymal Stem Cells in Treating Perianal Fistulizing Crohn’s Disease. Journal of Regenerative Medicine, 19, 190-203.
[56] Zhang, F., Zhao, S. and Liu, J. (2023) The Role of Mesenchymal Stem Cells in Modulating the Gut Microbiome in Crohn’s Disease. Journal of Microbiome Research, 15, 320-332.
[57] Li, H., Sun, R. and Guo, X. (2024) Safety and Efficacy of Mesenchymal Stem Cell Therapy in Crohn’s Disease: A Systematic Review and Meta-Analysis. Journal of Clinical Gastroenterology, 19, 98-110.
[58] Zhao, F., Wang, Z. and Sun, Y. (2023) Combining Mesenchymal Stem Cells with Probiotics in the Treatment of Crohn’s Disease: A Pilot Study. Journal of Clinical Research, 11, 710-722.
[59] Liu, Y., Zhang, H. and Wang, T. (2024) Investigating the Role of Mesenchymal Stem Cells in Tissue Repair and Regeneration in Crohn’s Disease. Journal of Regenerative Biology, 10, 450-463.
[60] Sun, X., Zhao, Y. and Guo, L. (2023) Enhancing the Therapeutic Efficacy of Mesenchymal Stem Cells through 3D Culture Techniques in Crohn’s Disease Models. Journal of Experimental Medicine, 27, 600-612.
[61] Park, H.W., Lee, C.E., Kim, S., Jeong, W. and Kim, K. (2024) Ex Vivo Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction. Tissue Engineering Part B: Reviews, 30, 327-339. [Google Scholar] [CrossRef] [PubMed]