Abstract
Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed.
Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC).
This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.
[http://dx.doi.org/10.1136/gutjnl-2015-309903] [PMID: 26353983]
[http://dx.doi.org/10.1016/S0140-6736(07)60750-8] [PMID: 17499605]
[http://dx.doi.org/10.1002/14651858.CD007443.pub2] [PMID: 22161412]
[http://dx.doi.org/10.25122/jml-2018-0075] [PMID: 31406511]
[http://dx.doi.org/10.1186/s12876-019-1058-1] [PMID: 31455284]
[http://dx.doi.org/10.1016/j.autrev.2013.06.002] [PMID: 23792214]
[http://dx.doi.org/10.1007/s12325-018-0795-9] [PMID: 30374806]
[http://dx.doi.org/10.1016/S0140-6736(16)31203-X] [PMID: 27477896]
[http://dx.doi.org/10.1093/ibd/izy269] [PMID: 30165490]
[http://dx.doi.org/10.1007/s11894-019-0689-2] [PMID: 31016396]
[http://dx.doi.org/10.7150/ijms.21666]
[http://dx.doi.org/10.1098/rstb.2017.0213]
[http://dx.doi.org/10.1155/2015/727542] [PMID: 26421301]
[http://dx.doi.org/10.2174/1574888X14666190411121528] [PMID: 30973112]
[http://dx.doi.org/10.4252/wjsc.v9.i8.107] [PMID: 28928907]
[http://dx.doi.org/10.2174/1574888X15666200914142709] [PMID: 32928093]
[http://dx.doi.org/10.1007/7651_2015_314] [PMID: 26892015]
[http://dx.doi.org/10.1155/2019/8106818]
[http://dx.doi.org/10.1038/aps.2013.50] [PMID: 23736003]
[http://dx.doi.org/10.3390/ijms20163876] [PMID: 31398940]
[http://dx.doi.org/10.1038/srep08713] [PMID: 25736907]
[http://dx.doi.org/10.5339/qproc.2012.stem.1.17]
[http://dx.doi.org/10.3389/fimmu.2017.00339]
[http://dx.doi.org/10.1155/2016/5303048] [PMID: 26925108]
[http://dx.doi.org/10.1002/stem.544] [PMID: 20945332]
[http://dx.doi.org/10.1002/sctm.19-0092] [PMID: 31702119]
[http://dx.doi.org/10.1182/blood-2004-04-1559] [PMID: 15494428]
[http://dx.doi.org/10.4049/jimmunol.0803864] [PMID: 19494321]
[http://dx.doi.org/10.1002/stem.1543] [PMID: 24105952]
[http://dx.doi.org/10.1002/stem.7] [PMID: 19353519]
[http://dx.doi.org/10.1634/stemcells.2007-0563] [PMID: 17916800]
[http://dx.doi.org/10.3389/fimmu.2012.00182]
[http://dx.doi.org/10.1002/stem.1563] [PMID: 24123639]
[http://dx.doi.org/10.1371/journal.pone.0010088] [PMID: 20436665]
[http://dx.doi.org/10.1186/s13287-020-01840-2] [PMID: 32988406]
[http://dx.doi.org/10.1038/nri3399] [PMID: 23435331]
[http://dx.doi.org/10.1038/ni.3002] [PMID: 25329189]
[http://dx.doi.org/10.1038/cdd.2012.26] [PMID: 22421969]
[http://dx.doi.org/10.1016/j.jcyt.2013.02.010] [PMID: 23602578]
[http://dx.doi.org/10.1634/stemcells.2007-0878] [PMID: 18292209]
[http://dx.doi.org/10.1634/stemcells.2007-0554] [PMID: 17932417]
[http://dx.doi.org/10.1016/j.ejcb.2019.04.002] [PMID: 31023504]
[http://dx.doi.org/10.1038/mt.2011.189] [PMID: 21934657]
[http://dx.doi.org/10.1002/stem.1432] [PMID: 23712682]
[http://dx.doi.org/10.1038/nri3209] [PMID: 22531326]
[http://dx.doi.org/10.1002/eji.200425405] [PMID: 15827960]
[http://dx.doi.org/10.1182/blood-2004-07-2921] [PMID: 15514012]
[http://dx.doi.org/10.4049/jimmunol.177.4.2080] [PMID: 16887966]
[http://dx.doi.org/10.1182/blood-2008-04-154138] [PMID: 18832657]
[http://dx.doi.org/10.1182/blood-2004-02-0586] [PMID: 15692068]
[http://dx.doi.org/10.1080/14653240701452057] [PMID: 17786606]
[http://dx.doi.org/10.1038/nri2395] [PMID: 19172693]
[http://dx.doi.org/10.3324/haematol.12857]
[http://dx.doi.org/10.1182/blood-2007-02-075481] [PMID: 17684157]
[http://dx.doi.org/10.2174/156652412800619950] [PMID: 22515979]
[http://dx.doi.org/10.3727/000000006780666957] [PMID: 17605296]
[http://dx.doi.org/10.1007/s00011-018-1205-0] [PMID: 30506263]
[http://dx.doi.org/10.5966/sctm.2016-0044] [PMID: 28170190]
[http://dx.doi.org/10.1038/gt.2008.101] [PMID: 18596829]
[http://dx.doi.org/10.1002/stem.2575] [PMID: 28294454]
[http://dx.doi.org/10.1155/2016/1929536] [PMID: 28105054]
[http://dx.doi.org/10.1182/blood-2005-07-2657] [PMID: 16141348]
[http://dx.doi.org/10.1111/j.1365-2249.2009.03874.x] [PMID: 19210524]
[http://dx.doi.org/10.4049/jimmunol.0902007] [PMID: 20511548]
[http://dx.doi.org/10.1186/s13287-015-0021-5] [PMID: 25890330]
[http://dx.doi.org/10.1002/eji.201242643] [PMID: 23161436]
[http://dx.doi.org/10.1002/stem.2485] [PMID: 27571579]
[http://dx.doi.org/10.1186/scrt216] [PMID: 23734780]
[http://dx.doi.org/10.1002/art.39069] [PMID: 25708718]
[http://dx.doi.org/10.1096/fj.15-273664] [PMID: 26038125]
[http://dx.doi.org/10.1038/cmi.2014.118] [PMID: 25482073]
[http://dx.doi.org/10.1111/cei.12120] [PMID: 23607314]
[http://dx.doi.org/10.1182/blood.V99.10.3838] [PMID: 11986244]
[http://dx.doi.org/10.1089/ten.2006.12.2263] [PMID: 16968166]
[http://dx.doi.org/10.1182/blood-2005-04-1496] [PMID: 15905186]
[http://dx.doi.org/10.1634/stemcells.2008-0687] [PMID: 19096038]
[http://dx.doi.org/10.4049/jimmunol.1202775] [PMID: 23589610]
[http://dx.doi.org/10.1016/j.stemcr.2013.06.006]
[http://dx.doi.org/10.1038/nm.1905] [PMID: 19098906]
[http://dx.doi.org/10.1186/s13287-018-1039-2] [PMID: 30359316]
[http://dx.doi.org/10.3389/fimmu.2016.00415]
[http://dx.doi.org/10.1097/01.TP.0000082540.43730.80] [PMID: 14578755]
[http://dx.doi.org/10.1053/j.gastro.2008.11.041] [PMID: 19135996]
[http://dx.doi.org/10.1155/2017/4960831] [PMID: 28642794]
[http://dx.doi.org/10.1002/stem.2779] [PMID: 29341339]
[http://dx.doi.org/10.3389/fimmu.2017.01042]
[http://dx.doi.org/10.1097/TP.0b013e3181fed001] [PMID: 21042238]
[http://dx.doi.org/10.1182/blood-2007-02-074997] [PMID: 17951526]
[http://dx.doi.org/10.1016/j.trim.2008.08.004] [PMID: 18762258]
[http://dx.doi.org/10.4049/jimmunol.1401776] [PMID: 25305313]
[http://dx.doi.org/10.1002/stem.2254] [PMID: 26661518]
[http://dx.doi.org/10.5966/sctm.2012-0166] [PMID: 23836805]
[http://dx.doi.org/10.1038/s41467-018-05167-8] [PMID: 30030423]
[http://dx.doi.org/10.3389/fimmu.2019.01191]
[http://dx.doi.org/10.1038/cdd.2013.149] [PMID: 24162664]
[http://dx.doi.org/10.1016/j.stem.2007.11.014] [PMID: 18371435]
[http://dx.doi.org/10.1038/nn.3109] [PMID: 22610068]
[http://dx.doi.org/10.1016/j.immuni.2011.06.011] [PMID: 21835648]
[http://dx.doi.org/10.1002/biof.1374] [PMID: 28718997]
[http://dx.doi.org/10.1038/srep38308] [PMID: 27910911]
[http://dx.doi.org/10.3109/14653249.2010.542456] [PMID: 21171824]
[http://dx.doi.org/10.1016/j.celrep.2017.08.089] [PMID: 28930684]
[http://dx.doi.org/10.1038/s41418-017-0006-2] [PMID: 29238069]
[http://dx.doi.org/10.1182/blood-2010-12-327353] [PMID: 21551236]
[http://dx.doi.org/10.1016/j.stem.2009.05.003] [PMID: 19570514]
[http://dx.doi.org/10.1002/art.10503] [PMID: 12355494]
[http://dx.doi.org/10.1186/s13287-018-0841-1] [PMID: 29625582]
[http://dx.doi.org/10.1074/jbc.M116.720953] [PMID: 27044744]
[http://dx.doi.org/10.1089/scd.2012.0395] [PMID: 23002959]
[http://dx.doi.org/10.1038/mt.2015.44] [PMID: 25868399]
[http://dx.doi.org/10.1016/j.ijcard.2014.12.043] [PMID: 25590961]
[http://dx.doi.org/10.1371/journal.pone.0061366] [PMID: 23593475]
[http://dx.doi.org/10.1016/j.stem.2012.03.007] [PMID: 22542159]
[http://dx.doi.org/10.1165/rcmb.2017-0326OC] [PMID: 29220578]
[http://dx.doi.org/10.1038/cr.2008.80] [PMID: 18607390]
[http://dx.doi.org/10.1016/j.jcyt.2017.02.233]
[http://dx.doi.org/10.1111/j.1365-2796.2007.01844.x] [PMID: 17949362]
[http://dx.doi.org/10.1126/scitranslmed.aam7828] [PMID: 29141887]
[http://dx.doi.org/10.2217/imt-2017-0117] [PMID: 29370720]
[http://dx.doi.org/10.3389/fimmu.2012.00212]
[http://dx.doi.org/10.1111/j.1365-2567.2007.02743.x] [PMID: 18067553]
[http://dx.doi.org/10.1136/gut.2010.214841] [PMID: 21257987]
[http://dx.doi.org/10.2217/rme.15.69] [PMID: 26387424]
[http://dx.doi.org/10.1111/j.1572-0241.1999.01288.x] [PMID: 10445543]
[http://dx.doi.org/10.1007/s11605-006-0021-y] [PMID: 17390181]
[http://dx.doi.org/10.1016/j.stemcr.2014.04.020]
[http://dx.doi.org/10.1186/s13287-016-0376-2] [PMID: 27515534]
[http://dx.doi.org/10.1007/s10620-016-4166-6] [PMID: 27107864]
[http://dx.doi.org/10.1016/S0140-6736(08)60690-X] [PMID: 18468541]
[http://dx.doi.org/10.1186/1476-9255-2-8] [PMID: 16045800]
[http://dx.doi.org/10.1002/art.27548] [PMID: 20506343]
[http://dx.doi.org/10.1016/j.jneuroim.2010.07.013] [PMID: 20728948]
[http://dx.doi.org/10.1016/j.cellimm.2015.01.002] [PMID: 25596473]
[http://dx.doi.org/10.1089/scd.2013.0554] [PMID: 24650034]
[http://dx.doi.org/10.1089/scd.2009.0345] [PMID: 19824807]
[http://dx.doi.org/10.1177/0963689718780304] [PMID: 30095002]
[http://dx.doi.org/10.1155/2017/5356760] [PMID: 28589143]
[http://dx.doi.org/10.3390/cells8070764] [PMID: 31340546]
[http://dx.doi.org/10.1155/2016/2640746] [PMID: 27057168]
[http://dx.doi.org/10.1007/s00383-020-04681-5] [PMID: 32448932]
[http://dx.doi.org/10.1007/s10620-018-5082-8] [PMID: 29704139]
[http://dx.doi.org/10.1093/ecco-jcc/jjz116] [PMID: 31197361]
[http://dx.doi.org/10.1016/j.mayocp.2015.03.023] [PMID: 26046409]
[http://dx.doi.org/10.1007/s10350-005-0052-6] [PMID: 15933795]
[http://dx.doi.org/10.1007/s00384-011-1350-1] [PMID: 22065114]
[http://dx.doi.org/10.3727/096368912X656045] [PMID: 23006344]
[http://dx.doi.org/10.1007/s10151-017-1630-z] [PMID: 28567691]
[http://dx.doi.org/10.1002/stem.1357] [PMID: 23404825]
[http://dx.doi.org/10.5966/sctm.2014-0199] [PMID: 25829404]
[http://dx.doi.org/10.1053/j.gastro.2017.04.001]
[http://dx.doi.org/10.1097/DCR.0b013e318255364a] [PMID: 22706128]
[http://dx.doi.org/10.1097/DCR.0000000000001333] [PMID: 30664554]
[http://dx.doi.org/10.1093/ibd/izz215] [PMID: 31605115]
[http://dx.doi.org/10.1007/DCR.0b013e3181973487] [PMID: 19273960]
[http://dx.doi.org/10.1053/j.gastro.2015.06.014]
[http://dx.doi.org/10.5966/sctm.2015-0356] [PMID: 27412883]
[http://dx.doi.org/10.5009/gnl17035] [PMID: 28873511]
[http://dx.doi.org/10.1097/MIB.0b013e31827f27df] [PMID: 23429460]
[http://dx.doi.org/10.1016/j.cgh.2013.06.021] [PMID: 23872668]
[http://dx.doi.org/10.1007/s00384-012-1581-9] [PMID: 23053677]
[http://dx.doi.org/10.1111/codi.13223] [PMID: 26603576]
[http://dx.doi.org/10.1053/j.gastro.2017.12.020]
[http://dx.doi.org/10.1111/codi.15324] [PMID: 32810356]
[http://dx.doi.org/10.1053/j.gastro.2019.02.005]
[http://dx.doi.org/10.1093/ecco-jcc/jjy220] [PMID: 30561580]
[http://dx.doi.org/10.1002/psb.1804]
[http://dx.doi.org/10.1080/17474124.2020.1764349] [PMID: 32354239]
[http://dx.doi.org/10.1111/codi.15587] [PMID: 33595166]
[http://dx.doi.org/10.1002/path.5357] [PMID: 31608444]
[http://dx.doi.org/10.1080/00365521.2017.1281434] [PMID: 28116942]
[http://dx.doi.org/10.15761/JSCRM.1000136]
[http://dx.doi.org/10.3389/fimmu.2018.01078]
[http://dx.doi.org/10.5009/gnl18438] [PMID: 31158947]
[http://dx.doi.org/10.7150/thno.47683]
[http://dx.doi.org/10.1186/s13287-020-02025-7] [PMID: 33256827]
[http://dx.doi.org/10.1186/s13287-015-0166-2]
[http://dx.doi.org/10.1136/gut.2010.215152] [PMID: 20921206]
[http://dx.doi.org/10.1111/apt.13717] [PMID: 27385373]
[http://dx.doi.org/10.1093/ecco-jcc/jjab076.417]
[http://dx.doi.org/10.1097/DCR.0000000000001863] [PMID: 33538521]