Efficacy of cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn’s disease—A prospective nationwide multicenter cohort study

Schwartz DA, Loftus EV Jr., Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology. 2002;122(4):875–80.

Article  PubMed  Google Scholar 

Bell SJ, Williams AB, Wiesel P, Wilkinson K, Cohen RC, Kamm MA. The clinical course of fistulating Crohn’s disease. Aliment Pharmacol Ther. 2003;17(9):1145–51.

Article  CAS  PubMed  Google Scholar 

Pearson DC, May GR, Fick GH, Sutherland LR. Azathioprine and 6‑mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med. 1995;123(2):132–42.

Article  CAS  PubMed  Google Scholar 

Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS. Treatment of Crohn’s disease with 6‑mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med. 1980;302(18):981–7.

Article  CAS  PubMed  Google Scholar 

Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340(18):1398–405.

Article  CAS  PubMed  Google Scholar 

Domenech E, Hinojosa J, Nos P, Garcia-Planella E, Cabre E, Bernal I, et al. Clinical evolution of luminal and perianal Crohn’s disease after inducing remission with infliximab: how long should patients be treated? Aliment Pharmacol Ther. 2005;22(11):1107–13.

Article  CAS  PubMed  Google Scholar 

Molendijk I, Nuij VJ, van der Meulen-de Jong AE, van der Woude CJ. Disappointing durable remission rates in complex Crohn’s disease fistula. Inflamm Bowel Dis. 2014;20(11):2022–8.

Article  PubMed  Google Scholar 

Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350(9):876–85.

Article  CAS  PubMed  Google Scholar 

Scharl M, Rogler G. Pathophysiology of fistula formation in Crohn’s disease. World J Gastrointest Pathophysiol. 2014;5(3):205–12.

Article  PubMed  PubMed Central  Google Scholar 

Garg P, Kaur B, Goyal A, Yagnik VD, Dawka S, Menon GR. Lessons learned from an audit of 1250 anal fistula patients operated at a single center: a retrospective review. World J Gastrointest Surg. 2021;13(4):340–54.

Article  PubMed  PubMed Central  Google Scholar 

Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011;6:457–78.

Article  CAS  PubMed  Google Scholar 

Garcia-Olmo D, Guadalajara H, Rubio-Perez I, Herreros MD, de-la-Quintana P, Garcia-Arranz M. Recurrent anal fistulae: limited surgery supported by stem cells. World J Gastroenterol. 2015;21(11):3330–6.

Article  PubMed  PubMed Central  Google Scholar 

Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, 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. Lancet. 2016;388(10051):1281–90.

Article  PubMed  Google Scholar 

Agha R, Abdall-Razak A, Crossley E, Dowlut N, Iosifidis C, Mathew G, et al. STROCSS 2019 guideline: strengthening the reporting of cohort studies in surgery. Int J Surg. 2019;72:156–65.

Article  PubMed  Google Scholar 

Carvello M, Lightner A, Yamamoto T, Kotze PG, Spinelli A. Mesenchymal stem cells for perianal Crohn’s disease. Cells. 2019;8(7):764. https://doi.org/10.3390/cells8070764.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371(9624):1579–86.

Article  CAS  PubMed  Google Scholar 

Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG‑6. Cell Stem Cell. 2009;5(1):54–63.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm. 2005;2:8.

Article  Google Scholar 

Yamout B, Hourani R, Salti H, Barada W, El-Hajj T, Al-Kutoubi A, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 2010;227(1–2):185–9.

Article  CAS  PubMed  Google Scholar 

Dai W, Hale SL, Martin BJ, Kuang JQ, Dow JS, Wold LE, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation. 2005;112(2):214–23.

Article  PubMed  Google Scholar 

Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007;149(2):353–63.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42–8.

Article  PubMed  Google Scholar 

Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T‑cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103(12):4619–21.

Article  CAS  PubMed  Google Scholar 

Horton JA, Hudak KE, Chung EJ, White AO, Scroggins BT, Burkeen JF, et al. Mesenchymal stem cells inhibit cutaneous radiation-induced fibrosis by suppressing chronic inflammation. Stem Cells. 2013;31(10):2231–41.

Article  CAS  PubMed  Google Scholar 

Garcia-Olmo D, Garcia-Arranz M, Garcia LG, Cuellar ES, Blanco IF, Prianes LA, et al. 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(5):451–4.

Article  PubMed  Google Scholar 

Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018;154(5):1334–42.e4.

Article  PubMed  Google Scholar 

Cabalzar-Wondberg D, Turina M, Biedermann L, Rogler G, Schreiner P. Allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulas in Crohn’s disease: a case series. Colorectal Dis. 2021;23(6):1444–50.

Article  PubMed  Google Scholar 

Schwandner O. Stem cell injection for complex anal fistula in Crohn’s disease: a single-center experience. World J Gastroenterol. 2021;27(24):3643–53.

Article  PubMed  PubMed Central  Google Scholar 

Nikolic M, Stift A, Reinisch W, Vogelsang H, Matic A, Muller C, et al. Allogeneic expanded adipose-derived stem cells in the treatment of rectovaginal fistulas in Crohn’s disease. Colorectal Dis. 2021;23(1):153–8.

Article  CAS  PubMed  Google Scholar 

Dietz AB, Dozois EJ, Fletcher JG, Butler GW, Radel D, Lightner AL, et al. Autologous mesenchymal stem cells, applied in a bioabsorbable matrix, for treatment of perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2017;153(1):59–62.e2.

Article  CAS  PubMed  Google Scholar 

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