Advances in adipose-derived mesenchymal stem cells for treating anal fistula in Crohn's disease
-
摘要: 克罗恩病肛瘘(perianal fistulizing Crohn's disease，PFCD)是克罗恩病(Crohn's disease，CD)常见的肛周并发症。其中约1/3的患者会反复发作，严重影响患者的生活质量。PFCD的传统治疗以药物及外科手术为主，但效果一般且复发率较高，创面较大。近年来，脂肪来源间充质干细胞(adipose-derived mesenchymal stem cells，ADMSC)在CD及PFCD的治疗中显示出显著效果。本文主要介绍应用ADMSC治疗CD及PFCD的基本原理和作用机制以及临床试验的最新结果，以期为ADMSC治疗PFCD的研究提供参考。
-
关键词:
- 脂肪来源间充质干细胞 /
- 克罗恩病 /
- 克罗恩病肛瘘 /
- 治疗
Abstract: Perianal fistulizing Crohn's disease(PFCD) is a common perianal complication of Crohn's disease(CD). About one-third of these patients will have repeated attacks, seriously affecting the quality of life of patients. The traditional treatment of PFCD is mainly drug and surgery, but the effect is general, the recurrence rate is high, and the wound is larger. In recent years, Adipose derived mesenchymal stem cells(ADMSC) have shown significant effects in the treatment of CD and PFCD. This article mainly introduces the basic principle and mechanism of ADMSC in the treatment of CD and PFCD and the latest results of clinical trials. Hope to provide reference for the study of ADMSC treatment of PFCD. -
-
[1] Mao F, Tu Q, Wang L, et al. Mesenchymal stem cells and their therapeutic applications in inflammatory bowel disease[J]. Oncotarget, 2017, 8(23): 38008-38021. doi: 10.18632/oncotarget.16682
[2] Chaparro M, Zanotti C, Burgueño P, et al. Health care costs of complex perianal fistula in Crohn's disease[J]. Dig Dis Sci, 2013, 58(12): 3400-3406. doi: 10.1007/s10620-013-2830-7
[3] Carvello M, Lightner A, Yamamoto T, et al. Mesenchymal Stem Cells for Perianal Crohn's Disease[J]. Cells, 2019, 8(7): 764. doi: 10.3390/cells8070764
[4] Malchow H, Ewe K, Brandes JW, et al. European Cooperative Crohn's Disease Study(ECCDS): results of drug treatment[J]. Gastroenterology, 1984, 86(2): 249-266. doi: 10.1016/0016-5085(84)90409-8
[5] Benchimol EI, Seow CH, Steinhart AH, et al. Traditional corticosteroids for induction of remission in Crohn's disease[J]. Cochrane Database Syst Rev, 2008, 2008(2): CD006792.
[6] 中华医学会消化病学分会炎症性肠病学组. 英夫利西治疗克罗恩病的推荐方案(2011年)[J]. 中华消化杂志, 2011, 31(12): 822-824.
[7] 吴开春, 梁洁, 冉志华, 等. 炎症性肠病诊断与治疗的共识意见(2018年·北京)[J]. 中国实用内科杂志, 2018, 38(9): 796-813. doi: 10.19538/j.nk2018090106
[8] 克罗恩病肛瘘共识专家组. 克罗恩病肛瘘诊断与治疗的专家共识意见[J]. 中华炎性肠病杂志, 2019, 3(2): 105-110. https://www.cnki.com.cn/Article/CJFDTOTAL-YXJK202009004.htm
[9] Schwartz DA, Loftus EV Jr, Tremaine WJ, et al. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota[J]. Gastroenterology, 2002, 122(4): 875-880. doi: 10.1053/gast.2002.32362
[10] 魏晓玲, 张志谦, 耿学斯. 干细胞移植治疗复杂性肛瘘的研究进展[J]. 中国普外基础与临床杂志, 2019, 26(7): 887-891. https://www.cnki.com.cn/Article/CJFDTOTAL-ZPWL201907025.htm
[11] Teixeira FG, Panchalingam KM, Anjo SI, et al. Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cell secretome?[J]. Stem Cell Res Ther, 2015, 6(1): 133. doi: 10.1186/s13287-015-0124-z
[12] Kisiel AH, McDuffee LA, Masaoud E, et al. Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum[J]. Am J Vet Res, 2012, 73(8): 1305-1317. doi: 10.2460/ajvr.73.8.1305
[13] Mrozik KM, Zilm PS, Bagley CJ, et al. Proteomic characterization of mesenchymal stem cell-like populations derived from ovine periodontal ligament, dental pulp, and bone marrow: analysis of differentially expressed proteins[J]. Stem Cells Dev, 2010, 19(10): 1485-1499. doi: 10.1089/scd.2009.0446
[14] Najimi M, Berardis S, El-Kehdy H, et al. Human liver mesenchymal stem/progenitor cells inhibit hepatic stellate cell activation: in vitro and in vivo evaluation[J]. Stem Cell Res Ther, 2017, 8(1): 131. doi: 10.1186/s13287-017-0575-5
[15] Nordgren TM, Bailey KL, Heires AJ, et al. Effects of Agricultural Organic Dusts on Human Lung-Resident Mesenchymal Stem(Stromal)Cell Function[J]. Toxicol Sci, 2018, 162(2): 635-644. doi: 10.1093/toxsci/kfx286
[16] Ulrich D, Muralitharan R, Gargett CE. Toward the use of endometrial and menstrual blood mesenchymal stem cells for cell-based therapies[J]. Expert Opin Biol Ther, 2013, 13(10): 1387-1400. doi: 10.1517/14712598.2013.826187
[17] García-Olmo D, García-Arranz M, García LG, et al. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy[J]. Int J Colorectal Dis, 2003, 18(5): 451-454. doi: 10.1007/s00384-003-0490-3
[18] Cho YB, Lee WY, Park KJ, et al. Autologous adipose tissue-derived stem cells for the treatment of Crohn's fistula: a phase Ⅰ clinical study[J]. Cell Transplant, 2013, 22(2): 279-285. doi: 10.3727/096368912X656045
[19] Dietz AB, Dozois EJ, Fletcher JG, et al. Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for Treatment of Perianal Fistulas in Patients With Crohn's Disease[J]. Gastroenterology, 2017, 153(1): 59-62.e2. doi: 10.1053/j.gastro.2017.04.001
[20] García-Olmo D, García-Arranz M, Herreros D, et al. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation[J]. Dis Colon Rectum, 2005, 48(7): 1416-1423. doi: 10.1007/s10350-005-0052-6
[21] 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. doi: 10.1007/DCR.0b013e3181973487
[22] Cho YB, Park KJ, Yoon SN, et al. Long-term results of adipose-derived stem cell therapy for the treatment of Crohn's fistula[J]. Stem Cells Transl Med, 2015, 4(5): 532-537. doi: 10.5966/sctm.2014-0199
[23] Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease[J]. Gut, 2011, 60(6): 788-798. doi: 10.1136/gut.2010.214841
[24] Lee WY, Park KJ, Cho YB, et al. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula[J]. Stem Cells, 2013, 31(11): 2575-2581. doi: 10.1002/stem.1357
[25] 谢明颢, 何晓生, 朱金玲, 等. 脂肪来源间充质干细胞治疗克罗恩病的实验研究[J]. 中华胃肠外科杂志, 2015, 18(1): 58-64.
[26] Zhang J, Lv S, Liu X, et al. Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn's Disease: A Randomized Controlled Clinical Trial[J]. Gut Liver, 2018, 12(1): 73-78. doi: 10.5009/gnl17035
[27] Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells(Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial[J]. Lancet, 2016, 388(10051): 1281-1290. doi: 10.1016/S0140-6736(16)31203-X
[28] Molendijk I, Bonsing BA, Roelofs H, et al. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease[J]. Gastroenterology, 2015, 149(4): 918-27.e6. doi: 10.1053/j.gastro.2015.06.014
[29] Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999, 284(5411): 143-147. doi: 10.1126/science.284.5411.143
[30] Grégoire C, Lechanteur C, Briquet A, et al. Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases[J]. Aliment Pharmacol Ther, 2017, 45(2): 205-221. doi: 10.1111/apt.13864
[31] Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science(IFATS)and the International Society for Cellular Therapy(ISCT)[J]. Cytotherapy, 2013, 15(6): 641-648. doi: 10.1016/j.jcyt.2013.02.006
[32] Miana VV, González E. Adipose tissue stem cells in regenerative medicine[J]. Ecancermedicalscience, 2018, 12: 822.
[33] Lombardi F, Palumbo P, Augello FR, et al. Secretome of Adipose Tissue-Derived Stem Cells(ASCs)as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables[J]. Int J Mol Sci, 2019, 20(15): 3721. doi: 10.3390/ijms20153721
[34] Mohamed-Ahmed S, Fristad I, Lie SA, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison[J]. Stem Cell Res Ther, 2018, 9(1): 168. doi: 10.1186/s13287-018-0914-1
[35] Serrero M, Grimaud F, Philandrianos C, et al. Long-term Safety and Efficacy of Local Microinjection Combining Autologous Microfat and Adipose-Derived Stromal Vascular Fraction for the Treatment of Refractory Perianal Fistula in Crohn's Disease[J]. Gastroenterology, 2019, 156(8): 2335-2337.e2. doi: 10.1053/j.gastro.2019.01.032
[36] 刘建伟, 刘建平, 吴玉怀. 间充质干细胞治疗克罗恩病相关性肛周瘘管的meta分析[J]. 临床荟萃, 2019, 34(4): 347-351. https://www.cnki.com.cn/Article/CJFDTOTAL-LCFC201904013.htm
[37] Kim A, Shim S, Kim MJ, et al. Mesenchymal stem cell-mediated Notch2 activation overcomes radiation-induced injury of the hematopoietic system[J]. Sci Rep, 2018, 8(1): 9277. doi: 10.1038/s41598-018-27666-w
[38] Munn DH, Mellor AL. IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance[J]. Trends Immunol, 2016, 37(3): 193-207. doi: 10.1016/j.it.2016.01.002
[39] DelaRosa O, Dalemans W, Lombardo E. Mesenchymal stem cells as therapeutic agents of inflammatory and autoimmune diseases[J]. Curr Opin Biotechnol, 2012, 23(6): 978-983. doi: 10.1016/j.copbio.2012.05.005
[40] Longhini A, Salazar TE, Vieira C, et al. Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horses[J]. PLoS One, 2019, 14(3): e0212642. doi: 10.1371/journal.pone.0212642
[41] Forbes GM, Sturm MJ, Leong RW, et al. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn's disease refractory to biologic therapy[J]. Clin Gastroenterol Hepatol, 2014, 12(1): 64-71. doi: 10.1016/j.cgh.2013.06.021
[42] García-Olmo D, García-Arranz M, Herreros D, et al. A phase Ⅰ clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation[J]. Dis Colon Rectum, 2005, 48(7): 1416-1423. doi: 10.1007/s10350-005-0052-6
[43] de la Portilla F, Alba F, García-Olmo D, et al. Expanded allogeneic adipose-derived stem cells(eASCs)for the treatment of complex perianal fistula in Crohn's disease: results from a multicenter phase Ⅰ/Ⅱa clinical trial[J]. Int J Colorectal Dis, 2013, 28(3): 313-323. doi: 10.1007/s00384-012-1581-9
[44] Panés J, García-Olmo D, Van Assche G, et al. Long-term Efficacy and Safety of Stem Cell Therapy(Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease[J]. Gastroenterology, 2018, 154(5): 1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020
[45] Lightner AL, Wang Z, Zubair AC, et al. A Systematic Review and Meta-analysis of Mesenchymal Stem Cell Injections for the Treatment of Perianal Crohn's Disease: Progress Made and Future Directions[J]. Dis Colon Rectum, 2018, 61(5): 629-640. doi: 10.1097/DCR.0000000000001093
[46] Colombo F, Cammarata F, Baldi C, et al. Stem Cell Injection for Complex Refractory Perianal Fistulas in Crohn's Disease: A Single Center Initial Experience[J]. Front Surg, 2022, 9: 834870. doi: 10.3389/fsurg.2022.834870
[47] Garcia-Olmo D, Gilaberte I, Binek M, et al. Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel(Mesenchymal Stem Cell Treatment)in Patients With Perianal Fistulizing Crohn's Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial[J]. Dis Colon Rectum, 2022, 65(5): 713-720. doi: 10.1097/DCR.0000000000002325
[48] Barnhoorn MC, Wasser M, Roelofs H, et al. Long-term Evaluation of Allogeneic Bone Marrow-derived Mesenchymal Stromal Cell Therapy for Crohn's Disease Perianal Fistulas[J]. J Crohns Colitis, 2020, 14(1): 64-70. doi: 10.1093/ecco-jcc/jjz116
[49] Herreros MD, Garcia-Olmo D, Guadalajara H, et al. Stem Cell Therapy: A Compassionate Use Program in Perianal Fistula[J]. Stem Cells Int, 2019, 2019: 6132340.
[50] Ciccocioppo R, Gallia A, Sgarella A, et al. Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells[J]. Mayo Clin Proc, 2015, 90(6): 747-755. doi: 10.1016/j.mayocp.2015.03.023
[51] El-Nakeep S. Stem Cell Therapy for the Treatment of Crohn's Disease; Current Obstacles and Future Hopes[J]. Curr Stem Cell Res Ther, 2022, 17(8): 727-733. doi: 10.2174/1574888X16666210910112403
[52] 涂超, 程芳. 人骨髓来源间充质干细胞外泌体与肿瘤生长的关系[J]. 基因组学与应用生物学, 2019, 38(6): 2842-2848. https://www.cnki.com.cn/Article/CJFDTOTAL-GXNB201906059.htm
[53] Molendijk I, van der Meulen-de Jong AE, Verspaget HW, et al. Standardization of mesenchymal stromal cell therapy for perianal fistulizing Crohn's disease[J]. Eur J Gastroenterol Hepatol, 2018, 30(10): 1148-1154. doi: 10.1097/MEG.0000000000001208
[54] Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease[J]. Aliment Pharmacol Ther, 2017, 45(7): 933-940.
[55] El-Matary W, Walters TD, Huynh HQ, et al. Higher Postinduction Infliximab Serum Trough Levels Are Associated With Healing of Fistulizing Perianal Crohn's Disease in Children[J]. Inflamm Bowel Dis, 2019, 25(1): 150-155.
[56] Domènech E, Hinojosa J, Nos P, et al. Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated?[J]. Aliment Pharmacol Ther, 2005, 22(11-12): 1107-1113.
[57] 张凤丽, 邵小虎, 任怀娟, 等. 低温制剂保存对脂肪间充质干细胞生物学特性的影响[J]. 中国组织工程研究, 2017, 21(33): 5255-5261. https://www.cnki.com.cn/Article/CJFDTOTAL-XDKF201733004.htm
[58] Sánchez-Salinas A, Cabañas-Perianes V, Blanquer M, et al. An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion[J]. Transfusion, 2012, 52(11): 2382-2386.
[59] Marquez-Curtis LA, Janowska-Wieczorek A, Mcgann LE, et al. Mesenchymal stromal cells derived from various tissues: biological, clinical and cryopreservation aspects[J]. Cryobiology, 2015, 71(2): 181-197.
-
计量
- 文章访问数: 898
- PDF下载数: 400
- 施引文献: 0
下载: