干细胞移植治疗炎症性肠病：造血干细胞和间充质干细胞的应用_West China Medical Journal

Authors：

 林艳 ,  郑长青

中国医科大学附属盛京医院第二消化内科（沈阳 110022）;

Corresponding author：

郑长青, Email: zhengcq@sj-hospital.org

Keywords：

炎症性肠病; 造血干细胞; 间充质干细胞; 移植; 治疗

DOI：

10.7507/1002-0179.20150163

Video：

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Abstract Full text Figures/Tables Video References Cited by

炎症性肠病（IBD）是一组病因未明的慢性非特异性肠道炎症性疾病，包括溃疡性结肠炎及克罗恩病，发病与遗传、环境、免疫、炎症反应等多方面的因素有关，在我国的发病率上升趋势也非常明显。现有的IBD治疗以药物治疗为主，主要包括氨基水杨酸制剂、糖皮质激素、免疫抑制剂、生物制剂等，近年来干细胞在IBD治疗中的作用得到越来越多的重视，而目前的研究多应用造血干细胞移植（HSCT）及间充质干细胞（MSC）来治疗IBD。HSCT用于治疗IBD的可能机制包括基因治疗、直接参与受损肠黏膜修复及调节T淋巴细胞功能等方面；MSC用于治疗IBD的可能机制包括在受损肠道局部定植参与修复、免疫调节功能及促进损伤局部微循环重建等功能。HSCT及MSC在IBD患者的治疗中具有广泛的前景和研究空间。现就干细胞在治疗IBD中的应用进行综述。

Citation： 林艳, 郑长青. 干细胞移植治疗炎症性肠病：造血干细胞和间充质干细胞的应用. West China Medical Journal, 2015, 30(3): 565-568. doi: 10.7507/1002-0179.20150163 Copy

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11.	刘静, 韩冬梅, 薛梅, 等. 脐带间充质干细胞输注治疗顽固性溃疡性结肠炎[J]. 组织工程与重建外科杂志, 2011, 7(5):258-260.
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1. APDW2004 Chinese IBD Working Group. Retrospective analysis of 515 cases of Crohn's disease hospitalization in China:nationwide study from 1990 to 2003[J]. J Gastroenterol Hepatol, 2006, 21(6):1009-1015.
2. Lok KH, Hung HG, Ng CH, et al. Epidemiology and clinical characteristics of ulcerative colitis in Chinese population:experience from a single center in Hong Kong[J]. J Gastroenterol Hepatol, 2008, 23(3):406-410.
3. Van Deen WK, Oikonomopoulos A, Hommes DW. Stem cell therapy in inflammatory bowel disease:which, when and how?[J]. Curr Opin Gastroenterol, 2013, 29(4):384-390.
4. Christophi GP, Rong R, Holtzapple PG, et al. Immune markers and differential signaling networks in ulcerative colitis and Crohn's disease[J]. Inflamm Bowel Dis, 2012, 18(12):2342-2356.
5. Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases[J]. Gastroenterology, 2011, 140(6):1756-1767.
6. Cario E. Commensal-innate immune miscommunication in IBD pathogenesis[J]. Dig Dis, 2012, 30(4):334-340.
7. 樊星, 翁谢川, 丁日高. 炎症性肠病病因研究进展[J]. 国际消化病杂志, 2013, 33(1):6-8, 16.
8. Drakos PE, Nagler A, Or R. Case of crohn's disease in bone marrow transplantation[J]. Am J Hematol, 1993, 43(2):157-158.
9. Kashyap A, Forman SJ. Autologous bone marrow transplantation for non-Hodgkin's lymphoma resulting in long-term remission of coincidental Crohn's disease[J]. Br J Haematol, 1998, 103(3):651-652.
10. Oyama Y, Craig RM, Traynor AE, et al. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease[J]. Gastroenterology, 2005, 128(3):552-563.
11. 刘静, 韩冬梅, 薛梅, 等. 脐带间充质干细胞输注治疗顽固性溃疡性结肠炎[J]. 组织工程与重建外科杂志, 2011, 7(5):258-260.
12. Copelan EA. Hematopoietic stem-cell transplantation[J]. N Engl J Med, 2006, 354(17):1813-1826.
13. Snowden JA, Saccardi R, Allez M, et al. Haematopoietic SCT in severe autoimmune diseases:updated guidelines of the European Group for Blood and Marrow Transplantation[J]. Bone Marrow Transplant, 2012, 47(6):770-790.
14. Khalil PN, Weiler V, Nelson PJ, et al. Nonmyeloablative stem cell therapy enhances microcirculation and tissue regeneration in murine inflammatory bowel disease[J]. Gastroenterology, 2007, 132(3):944-954.
15. Monteleone G, Caruso R, Fina D, et al. Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21[J]. Gut, 2006, 55(12):1774-1780.
16. Muraro PA, Douek DC, Packer A, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients[J]. J Exp Med, 2005, 201(5):805-816.
17. Alexander T, Thiel A, Rosen O, et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo Generation of a juvenile and tolerant immune system[J]. Blood, 2009, 113(1):214-223.
18. Burt RK, Craig RM, Milanetti F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease:long-term follow-up[J]. Blood, 2010, 116(26):6123-6132.
19. Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system[J]. Nat Rev Immunol, 2012, 12(5):383-396.
20. Okamoto R, Yajima T, Yamazaki M, et al. Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract[J]. Nat Med, 2002, 8(9):1011-1017.
21. Yabana T, Arimura Y, Tanaka H, et al. Enhancing epithelia1 engraftment of rat mesenchymal stem cells restores epithelial barrier integrity[J]. J Pathol, 2009, 218(3):350-359.
22. 段江洁, 王蓓, 张建华, 等. 胎儿肠壁结缔组织诱导骨髓间充质干细胞向肠上皮细胞的分化[J]. 第三军医大学学报, 2008, 30(18):1718-1721.
23. English K. Mechanisms of mesenchymal stromal cell immunomodulation[J]. Immunol Cell Biol, 2013, 91(1):19-26.
24. Dazzi F, Lopes L, Weng L. Mesenchymal stromal cells:a key player in "innate tolerance"?[J]. Immunology, 2012, 137(3):206-213.
25. Duijvestein M, Wildenberg ME, Welling MM, et al. Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis[J]. Stem Cells, 2011, 29(10):1549-1558.
26. Brittan M, Hunt T, Jeffery R, et al. Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon[J]. Gut, 2002, 50(6):752-757.
27. Andoh A, Bamba S, Brittan M, et al. Role of intestinal subepithelial myofibrob1asts in inflammation and regenerative response in the gut[J]. Pharmacol Ther, 2007, 114(1):94-106.
28. Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease:a phase Ⅱ study[J]. Lancet, 2008, 371(9624):1579-1586.
29. Bernardo ME, Ball LM, Cometa AM, et al. Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation[J]. Bone Marrow Transplant, 2011, 46(2):200-207.
30. Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula:a phase Ⅱ clinical trial[J]. Dis Colon Rectum, 2009, 52(1):79-86.
31. Guadalajara H, Herreros D, De-La-Quintana PA, et al. Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas[J]. Int J Colorectal Dis, 2012, 27(5):595-600.
32. Liang J, Zhang H, Wang D, et al. Allogeneic mesenchymal stem cell transplantation in seven patients with refractory inflammatory bowel disease[J]. Gut, 2012, 61(3):468-469.
33. Lalu MM, Mclntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell):a systematic review and meta-analysis of clinical trials[J]. PLoS One, 2012, 7(10):e47559.

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West China Medical Journal

干细胞移植治疗炎症性肠病：造血干细胞和间充质干细胞的应用

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