One more chance of fistula healing in inflammatory bowel disease:Stem cell therapy
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摘要
Patients with fistulizing inflammatory bowel disease are traditionally difficult to treat. This patient population often experiences delayed or insufficient healing of fistulas using current standard regimens including anti-biotics, immunomodulators, anti-tumor necrosis factor--α drug, placement of setons, and surgical repair. Several studies over the last ten to fifteen years have been conducted using stem cell therapies with promising results in this patient population. These studies show stem cell therapy in fistulizing disease to be successful in healing between 60%--88% compared to currently 50% with infliximab. Moreover, remission was seen 24 wk to 52 wk in these studies. Further research with a multi--approach treatment using medications, stem cell therapy, and surgical interventions will likely be the future of this innovative treatment approach.
Patients with fistulizing inflammatory bowel disease are traditionally difficult to treat. This patient population often experiences delayed or insufficient healing of fistulas using current standard regimens including anti-biotics, immunomodulators, anti-tumor necrosis factor--α drug, placement of setons, and surgical repair. Several studies over the last ten to fifteen years have been conducted using stem cell therapies with promising results in this patient population. These studies show stem cell therapy in fistulizing disease to be successful in healing between 60%--88% compared to currently 50% with infliximab. Moreover, remission was seen 24 wk to 52 wk in these studies. Further research with a multi--approach treatment using medications, stem cell therapy, and surgical interventions will likely be the future of this innovative treatment approach.
Patients with fistulizing inflammatory bowel disease are traditionally difficult to treat. This patient population often experiences delayed or insufficient healing of fistulas using current standard regimens including anti-biotics, immunomodulators, anti-tumor necrosis factor--α drug, placement of setons, and surgical repair. Several studies over the last ten to fifteen years have been conducted using stem cell therapies with promising results in this patient population. These studies show stem cell therapy in fistulizing disease to be successful in healing between 60%--88% compared to currently 50% with infliximab. Moreover, remission was seen 24 wk to 52 wk in these studies. Further research with a multi--approach treatment using medications, stem cell therapy, and surgical interventions will likely be the future of this innovative treatment approach.
引文
1 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 Panes J.Stem Cell Therapy for Perianal Fistulas in Crohn’s Disease.Gastroenterol Hepatol(N Y)2016;12:637-640[PMID:27917079]
3 De Francesco F,Romano M,Zarantonello L,Ruffolo C,Neri D,Bassi N,Giordano A,Zanus G,Ferraro GA,Cillo U.The role of adipose stem cells in inflammatory bowel disease:From biology to novel therapeutic strategies.Cancer Biol Ther 2016;17:889-898[PMID:27414952 DOI:10.1080/15384047.2016.1210741]
4 Dothel G,Raschi E,Rimondini R,De Ponti F.Mesenchymal stromal cell-based therapy:Regulatory and translational aspects in gastroenterology.World J Gastroenterol 2016;22:9057-9068[PMID:27895395 DOI:10.3748/wjg.v22.i41.9057]
5 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 J Colorectal Dis 2003;18:451-454[PMID:12756590 DOI:10.1007/s00384-003-0490-3]
6 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]
7 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]
8 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 Med 2015;4:532-537[PMID:25829404 DOI:10.5966/sctm.2014-0199]
9 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.Gastroenterology2017;153:59-62.e2[PMID:28400193 DOI:10.1053/j.gastro.2017.04.001]
10 Ciccocioppo R,Gallia A,Sgarella A,Kruzliak P,Gobbi PG,Corazza GR.Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells.Mayo Clin Proc 2015;90:747-755[PMID:26046409DOI:10.1016/j.mayocp.2015.03.023]
11 García-Arranz M,Herreros MD,González-Gómez C,de la Quintana P,Guadalajara H,Georgiev-Hristov T,Trébol J,GarciaOlmo D.Treatment of Crohn’s-Related Rectovaginal Fistula With Allogeneic Expanded-Adipose Derived Stem Cells:A Phase I-IIa Clinical Trial.Stem Cells Transl Med 2016;5:1441-1446[PMID:27412883 DOI:10.5966/sctm.2015-0356]
12 de la Portilla F,Alba F,García-Olmo D,Herrerías JM,González FX,Galindo A.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.Int J Colorectal Dis 2013;28:313-323[PMID:23053677 DOI:10.1007/s00384-012-1581-9]
13 Panés J,García-Olmo D,Van Assche G,Colombel JF,Reinisch W,Baumgart DC,Dignass A,Nachury M,Ferrante M,Kazemi-Shirazi L,Grimaud JC,de la Portilla F,Goldin E,Richard MP,Leselbaum A,Danese S;ADMIRE CD Study Group Collaborators.Expanded allogeneic adipose-derived mesenchymal stem cells(Cx601)for complex perianal fistulas in Crohn’s disease:a phase 3 randomised,double-blind controlled trial.Lancet 2016;388:1281-1290[PMID:27477896 DOI:10.1016/S0140-6736(16)31203-X]
14 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]
15 Wainstein C,Quera R,FluxáD,Kronberg U,Conejero A,LópezK?stner F,Jofre C,Zarate AJ.Stem Cell Therapy in Refractory Perineal Crohn’s Disease:Long-term Follow-up.Colorectal Dis2018[PMID:29316139 DOI:10.1111/codi.14002]
16 Sanz-Baro R,García-Arranz M,Guadalajara H,de la Quintana P,Herreros MD,García-Olmo D.First-in-Human Case Study:Pregnancy in Women With Crohn’s Perianal Fistula Treated With Adipose-Derived Stem Cells:A Safety Study.Stem Cells Transl Med 2015;4:598-602[PMID:25925838 DOI:10.5966/sctm.2014-0255]
17 Tsuchiya A,Kojima Y,Ikarashi S,Seino S,Watanabe Y,Kawata Y,Terai S.Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases.Inflamm Regen 2017;37:16[PMID:29259715 DOI:10.1186/s41232-017-0045-6]
2 Panes J.Stem Cell Therapy for Perianal Fistulas in Crohn’s Disease.Gastroenterol Hepatol(N Y)2016;12:637-640[PMID:27917079]
3 De Francesco F,Romano M,Zarantonello L,Ruffolo C,Neri D,Bassi N,Giordano A,Zanus G,Ferraro GA,Cillo U.The role of adipose stem cells in inflammatory bowel disease:From biology to novel therapeutic strategies.Cancer Biol Ther 2016;17:889-898[PMID:27414952 DOI:10.1080/15384047.2016.1210741]
4 Dothel G,Raschi E,Rimondini R,De Ponti F.Mesenchymal stromal cell-based therapy:Regulatory and translational aspects in gastroenterology.World J Gastroenterol 2016;22:9057-9068[PMID:27895395 DOI:10.3748/wjg.v22.i41.9057]
5 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 J Colorectal Dis 2003;18:451-454[PMID:12756590 DOI:10.1007/s00384-003-0490-3]
6 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]
7 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]
8 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 Med 2015;4:532-537[PMID:25829404 DOI:10.5966/sctm.2014-0199]
9 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.Gastroenterology2017;153:59-62.e2[PMID:28400193 DOI:10.1053/j.gastro.2017.04.001]
10 Ciccocioppo R,Gallia A,Sgarella A,Kruzliak P,Gobbi PG,Corazza GR.Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells.Mayo Clin Proc 2015;90:747-755[PMID:26046409DOI:10.1016/j.mayocp.2015.03.023]
11 García-Arranz M,Herreros MD,González-Gómez C,de la Quintana P,Guadalajara H,Georgiev-Hristov T,Trébol J,GarciaOlmo D.Treatment of Crohn’s-Related Rectovaginal Fistula With Allogeneic Expanded-Adipose Derived Stem Cells:A Phase I-IIa Clinical Trial.Stem Cells Transl Med 2016;5:1441-1446[PMID:27412883 DOI:10.5966/sctm.2015-0356]
12 de la Portilla F,Alba F,García-Olmo D,Herrerías JM,González FX,Galindo A.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.Int J Colorectal Dis 2013;28:313-323[PMID:23053677 DOI:10.1007/s00384-012-1581-9]
13 Panés J,García-Olmo D,Van Assche G,Colombel JF,Reinisch W,Baumgart DC,Dignass A,Nachury M,Ferrante M,Kazemi-Shirazi L,Grimaud JC,de la Portilla F,Goldin E,Richard MP,Leselbaum A,Danese S;ADMIRE CD Study Group Collaborators.Expanded allogeneic adipose-derived mesenchymal stem cells(Cx601)for complex perianal fistulas in Crohn’s disease:a phase 3 randomised,double-blind controlled trial.Lancet 2016;388:1281-1290[PMID:27477896 DOI:10.1016/S0140-6736(16)31203-X]
14 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]
15 Wainstein C,Quera R,FluxáD,Kronberg U,Conejero A,LópezK?stner F,Jofre C,Zarate AJ.Stem Cell Therapy in Refractory Perineal Crohn’s Disease:Long-term Follow-up.Colorectal Dis2018[PMID:29316139 DOI:10.1111/codi.14002]
16 Sanz-Baro R,García-Arranz M,Guadalajara H,de la Quintana P,Herreros MD,García-Olmo D.First-in-Human Case Study:Pregnancy in Women With Crohn’s Perianal Fistula Treated With Adipose-Derived Stem Cells:A Safety Study.Stem Cells Transl Med 2015;4:598-602[PMID:25925838 DOI:10.5966/sctm.2014-0255]
17 Tsuchiya A,Kojima Y,Ikarashi S,Seino S,Watanabe Y,Kawata Y,Terai S.Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases.Inflamm Regen 2017;37:16[PMID:29259715 DOI:10.1186/s41232-017-0045-6]