Review of stem cells as promising therapy for perianal disease in inflammatory bowel disease
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摘要
Those patients with perianal Crohn's disease or ul-cerative colitis experience a difficult to treat disease process with a delayed state and often inability to heal despite current therapies. The approaches currently used to treat these patients with corticosteroids,antibiotics,immunomodulators, anti-tumor necrosis factor-α drug, and surgical repair are limited in their healing ability. This review presents all current literature since emergence in the early 2000s of stem cell therapy for patients with perianal inflammatory bowel disease and analyzes the efficacy, outcomes and safety within these studies.
Those patients with perianal Crohn's disease or ul-cerative colitis experience a difficult to treat disease process with a delayed state and often inability to heal despite current therapies. The approaches currently used to treat these patients with corticosteroids,antibiotics,immunomodulators, anti-tumor necrosis factor-α drug, and surgical repair are limited in their healing ability. This review presents all current literature since emergence in the early 2000s of stem cell therapy for patients with perianal inflammatory bowel disease and analyzes the efficacy, outcomes and safety within these studies.
Those patients with perianal Crohn's disease or ul-cerative colitis experience a difficult to treat disease process with a delayed state and often inability to heal despite current therapies. The approaches currently used to treat these patients with corticosteroids,antibiotics,immunomodulators, anti-tumor necrosis factor-α drug, and surgical repair are limited in their healing ability. This review presents all current literature since emergence in the early 2000s of stem cell therapy for patients with perianal inflammatory bowel disease and analyzes the efficacy, outcomes and safety within these studies.
引文
1 Jiang XX,Zhang Y,Liu B,Zhang SX,Wu Y,Yu XD,Mao N.Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells.Blood 2005;105:4120-4126[PMID:15692068 DOI:10.1182/blood-2004-02-0586]
2 Beyth S,Borovsky Z,Mevorach D,Liebergall M,Gazit Z,Aslan H,Galun E,Rachmilewitz J.Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness.Blood 2005;105:2214-2219[PMID:15514012DOI:10.1182/blood-2004-07-2921]
3 Spaggiari GM,Abdelrazik H,Becchetti F,Moretta L.MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs:central role of MSC-derived prostaglandin E2.Blood 2009;113:6576-6583[PMID:19398717 DOI:10.1182/blood-2009-02-203943]
4 Melief SM,Geutskens SB,Fibbe WE,Roelofs H.Multipotent stromal cells skew monocytes towards an anti-inflammatory function:the link with key immunoregulatory molecules.Haematologica2013;98:e121-e122[PMID:24006414 DOI:10.3324/haematol.2013.093864]
5 Melief SM,Geutskens SB,Fibbe WE,Roelofs H.Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6.Haematologica 2013;98:888-895[PMID:23349310 DOI:10.3324/haematol.2012.078055]
6 Melief SM,Schrama E,Brugman MH,Tiemessen MM,Hoogduijn MJ,Fibbe WE,Roelofs H.Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages.Stem Cells 2013;31:1980-1991[PMID:23712682 DOI:10.1002/stem.1432]
7 Chapel A,Bertho JM,Bensidhoum M,Fouillard L,Young RG,Frick J,Demarquay C,Cuvelier F,Mathieu E,Trompier F,Dudoignon N,Germain C,Mazurier C,Aigueperse J,Borneman J,Gorin NC,Gourmelon P,Thierry D.Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome.J Gene Med 2003;5:1028-1038[PMID:14661178 DOI:10.1002/jgm.452]
8 García-Olmo D,García-Arranz M,García LG,Cuellar ES,Blanco IF,Prianes LA,Montes JA,Pinto FL,Marcos DH,García-Sancho L.Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease:a new cell-based therapy.Int JColorectal Dis 2003;18:451-454[PMID:12756590 DOI:10.1007/s00384-003-0490-3]
9 García-Olmo D,García-Arranz M,Herreros D,Pascual I,Peiro C,Rodríguez-Montes JA.A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation.Dis Colon Rectum 2005;48:1416-1423[PMID:15933795 DOI:10.1007/s10350-005-0052-6]
10 Garcia-Olmo D,Herreros D,Pascual I,Pascual JA,Del-Valle E,Zorrilla J,De-La-Quintana P,Garcia-Arranz M,Pascual M.Expanded adipose-derived stem cells for the treatment of complex perianal fistula:a phase II clinical trial.Dis Colon Rectum 2009;52:79-86[PMID:19273960 DOI:10.1007/DCR.0b013e3181973487]
11 Cho YB,Lee WY,Park KJ,Kim M,Yoo HW,Yu CS.Autologous adipose tissue-derived stem cells for the treatment of Crohn’s fistula:a phase I clinical study.Cell Transplant 2013;22:279-285[PMID:23006344 DOI:10.3727/096368912X656045]
12 Lee WY,Park KJ,Cho YB,Yoon SN,Song KH,Kim DS,Jung SH,Kim M,Yoo HW,Kim I,Ha H,Yu CS.Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn’s fistula.Stem Cells 2013;31:2575-2581[PMID:23404825 DOI:10.1002/stem.1357]
13 Cho YB,Park KJ,Yoon SN,Song KH,Kim DS,Jung SH,Kim M,Jeong HY,Yu CS.Long-term results of adipose-derived stem cell therapy for the treatment of Crohn’s fistula.Stem Cells Transl Med2015;4:532-537[PMID:25829404 DOI:10.5966/sctm.2014-0199]
14 Dietz AB,Dozois EJ,Fletcher JG,Butler GW,Radel D,Lightner AL,Dave M,Friton J,Nair A,Camilleri ET,Dudakovic A,van Wijnen AJ,Faubion WA.Autologous Mesenchymal Stem Cells,Applied in a Bioabsorbable Matrix,for Treatment of Perianal Fistulas in Patients With Crohn’s Disease.Gastroenterology 2017;153:59-62.e2[PMID:28400193 DOI:10.1053/j.gastro.2017.04.001]
15 Ciccocioppo R,Bernardo ME,Sgarella A,Maccario R,Avanzini MA,Ubezio C,Minelli A,Alvisi C,Vanoli A,Calliada F,Dionigi P,Perotti C,Locatelli F,Corazza GR.Autologous bone marrowderived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease.Gut 2011;60:788-798[PMID:21257987 DOI:10.1136/gut.2010.214841]
16 Panés J,García-Olmo D,Van Assche G,Colombel JF,Reinisch W,Baumgart DC,Dignass A,Nachury M,Ferrante M,KazemiShirazi L,Grimaud JC,de la Portilla F,Goldin E,Richard MP,Diez MC,Tagarro I,Leselbaum A,Danese S;ADMIRE CD Study Group Collaborators.Long-term Efficacy and Safety of Stem Cell Therapy(Cx601)for Complex Perianal Fistulas in Patients With Crohn’s Disease.Gastroenterology 2018;154:1334-1342.e4[PMID:29277560 DOI:10.1053/j.gastro.2017.12.020]
17 Molendijk I,Bonsing BA,Roelofs H,Peeters KC,Wasser MN,Dijkstra G,van der Woude CJ,Duijvestein M,Veenendaal RA,Zwaginga JJ,Verspaget HW,Fibbe WE,van der Meulen-de Jong AE,Hommes DW.Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn’s Disease.Gastroenterology 2015;149:918-927.e6[PMID:26116801 DOI:10.1053/j.gastro.2015.06.014]
2 Beyth S,Borovsky Z,Mevorach D,Liebergall M,Gazit Z,Aslan H,Galun E,Rachmilewitz J.Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness.Blood 2005;105:2214-2219[PMID:15514012DOI:10.1182/blood-2004-07-2921]
3 Spaggiari GM,Abdelrazik H,Becchetti F,Moretta L.MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs:central role of MSC-derived prostaglandin E2.Blood 2009;113:6576-6583[PMID:19398717 DOI:10.1182/blood-2009-02-203943]
4 Melief SM,Geutskens SB,Fibbe WE,Roelofs H.Multipotent stromal cells skew monocytes towards an anti-inflammatory function:the link with key immunoregulatory molecules.Haematologica2013;98:e121-e122[PMID:24006414 DOI:10.3324/haematol.2013.093864]
5 Melief SM,Geutskens SB,Fibbe WE,Roelofs H.Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6.Haematologica 2013;98:888-895[PMID:23349310 DOI:10.3324/haematol.2012.078055]
6 Melief SM,Schrama E,Brugman MH,Tiemessen MM,Hoogduijn MJ,Fibbe WE,Roelofs H.Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages.Stem Cells 2013;31:1980-1991[PMID:23712682 DOI:10.1002/stem.1432]
7 Chapel A,Bertho JM,Bensidhoum M,Fouillard L,Young RG,Frick J,Demarquay C,Cuvelier F,Mathieu E,Trompier F,Dudoignon N,Germain C,Mazurier C,Aigueperse J,Borneman J,Gorin NC,Gourmelon P,Thierry D.Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome.J Gene Med 2003;5:1028-1038[PMID:14661178 DOI:10.1002/jgm.452]
8 García-Olmo D,García-Arranz M,García LG,Cuellar ES,Blanco IF,Prianes LA,Montes JA,Pinto FL,Marcos DH,García-Sancho L.Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease:a new cell-based therapy.Int JColorectal Dis 2003;18:451-454[PMID:12756590 DOI:10.1007/s00384-003-0490-3]
9 García-Olmo D,García-Arranz M,Herreros D,Pascual I,Peiro C,Rodríguez-Montes JA.A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation.Dis Colon Rectum 2005;48:1416-1423[PMID:15933795 DOI:10.1007/s10350-005-0052-6]
10 Garcia-Olmo D,Herreros D,Pascual I,Pascual JA,Del-Valle E,Zorrilla J,De-La-Quintana P,Garcia-Arranz M,Pascual M.Expanded adipose-derived stem cells for the treatment of complex perianal fistula:a phase II clinical trial.Dis Colon Rectum 2009;52:79-86[PMID:19273960 DOI:10.1007/DCR.0b013e3181973487]
11 Cho YB,Lee WY,Park KJ,Kim M,Yoo HW,Yu CS.Autologous adipose tissue-derived stem cells for the treatment of Crohn’s fistula:a phase I clinical study.Cell Transplant 2013;22:279-285[PMID:23006344 DOI:10.3727/096368912X656045]
12 Lee WY,Park KJ,Cho YB,Yoon SN,Song KH,Kim DS,Jung SH,Kim M,Yoo HW,Kim I,Ha H,Yu CS.Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn’s fistula.Stem Cells 2013;31:2575-2581[PMID:23404825 DOI:10.1002/stem.1357]
13 Cho YB,Park KJ,Yoon SN,Song KH,Kim DS,Jung SH,Kim M,Jeong HY,Yu CS.Long-term results of adipose-derived stem cell therapy for the treatment of Crohn’s fistula.Stem Cells Transl Med2015;4:532-537[PMID:25829404 DOI:10.5966/sctm.2014-0199]
14 Dietz AB,Dozois EJ,Fletcher JG,Butler GW,Radel D,Lightner AL,Dave M,Friton J,Nair A,Camilleri ET,Dudakovic A,van Wijnen AJ,Faubion WA.Autologous Mesenchymal Stem Cells,Applied in a Bioabsorbable Matrix,for Treatment of Perianal Fistulas in Patients With Crohn’s Disease.Gastroenterology 2017;153:59-62.e2[PMID:28400193 DOI:10.1053/j.gastro.2017.04.001]
15 Ciccocioppo R,Bernardo ME,Sgarella A,Maccario R,Avanzini MA,Ubezio C,Minelli A,Alvisi C,Vanoli A,Calliada F,Dionigi P,Perotti C,Locatelli F,Corazza GR.Autologous bone marrowderived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease.Gut 2011;60:788-798[PMID:21257987 DOI:10.1136/gut.2010.214841]
16 Panés J,García-Olmo D,Van Assche G,Colombel JF,Reinisch W,Baumgart DC,Dignass A,Nachury M,Ferrante M,KazemiShirazi L,Grimaud JC,de la Portilla F,Goldin E,Richard MP,Diez MC,Tagarro I,Leselbaum A,Danese S;ADMIRE CD Study Group Collaborators.Long-term Efficacy and Safety of Stem Cell Therapy(Cx601)for Complex Perianal Fistulas in Patients With Crohn’s Disease.Gastroenterology 2018;154:1334-1342.e4[PMID:29277560 DOI:10.1053/j.gastro.2017.12.020]
17 Molendijk I,Bonsing BA,Roelofs H,Peeters KC,Wasser MN,Dijkstra G,van der Woude CJ,Duijvestein M,Veenendaal RA,Zwaginga JJ,Verspaget HW,Fibbe WE,van der Meulen-de Jong AE,Hommes DW.Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn’s Disease.Gastroenterology 2015;149:918-927.e6[PMID:26116801 DOI:10.1053/j.gastro.2015.06.014]