Cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn’s disease

References

• Schwartz DA, Loftus EV Jr., Tremaine WJ, et al.The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology. 2002;122(4):875–880.
   PubMed Web of Science ®Google Scholar
• Hellers G, Bergstrand O, Ewerth S, et al. Occurrence and outcome after primary treatment of anal fistulae in Crohn’s disease. Gut. 1980;21(6):525–527.
   PubMed Web of Science ®Google Scholar
• Buchmann P, Keighley MR, Allan RN, et al. Natural history of perianal Crohn’s disease. Ten year follow-up: a plea for conservatism. Am J Surg. 1980;140(5):642–644.
   PubMed Web of Science ®Google Scholar
• Makowiec F, Jehle EC, Starlinger M Clinical course of perianal fistulas in Crohn’s disease. Gut. 1995;37(5):696–701.
   PubMed Web of Science ®Google Scholar
• Bell SJ, Williams AB, Wiesel P, et al. The clinical course of fistulating Crohn’s disease. Aliment Pharmacol Ther. 2003;17(9):1145–1151.
   PubMed Web of Science ®Google Scholar
• Michelassi F, Melis M, Rubin M, et al. Surgical treatment of anorectal complications in Crohn’s disease. Surgery. 2000;128(4):597–603.
   PubMed Web of Science ®Google Scholar
• Parks AG, Gordon PH, Hardcastle JD A classification of fistula-in-ano. Br J Surg. 1976;63(1):1–12.
   PubMed Web of Science ®Google Scholar
• Molendijk I, Nuij VJ, van der Meulen-de Jong AE, et al. Disappointing durable remission rates in complex Crohn’s disease fistula. Inflamm Bowel Dis. 2014;20(11):2022–2028.
   PubMed Web of Science ®Google Scholar
• Schwartz DA, Herdman CR Review article: the medical treatment of Crohn’s perianal fistulas. Aliment Pharmacol Ther. 2004;19(9):953–967.
   PubMed Web of Science ®Google Scholar
• Jones JH, Lennard-Jones JE Corticosteroids and corticotrophin in the treatment of Crohn’s disease. Gut. 1966;7(2):181–187.
   PubMed Web of Science ®Google Scholar
• Brandt LJ, Bernstein LH, Boley SJ, et al. Metronidazole therapy for perineal Crohn’s disease: a follow-up study. Gastroenterology. 1982;83(2):383–387.
   PubMed Web of Science ®Google Scholar
• Bernstein LH, Frank MS, Brandt LJ, et al. Healing of perineal Crohn’s disease with metronidazole. Gastroenterology. 1980;79(3):599.
   PubMed Web of Science ®Google Scholar
• Jakobovits J, Schuster MM Metronidazole therapy for Crohn’s disease and associated fistulae. Am J Gastroenterol. 1984;79(7):533–540.
   PubMed Web of Science ®Google Scholar
• Hanauer SB, Smith MB Rapid closure of Crohn’s disease fistulas with continuous intravenous cyclosporin A. Am J Gastroenterol. 1993;88(5):646–649.
   PubMed Web of Science ®Google Scholar
• Present DH, Lichtiger S Efficacy of cyclosporine in treatment of fistula of Crohn’s disease. Dig Dis Sci. 1994;39(2):374–380.
   PubMed Web of Science ®Google Scholar
• Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut. 2014;63(9):1381–1392.
   PubMed Web of Science ®Google Scholar
• Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340(18):1398–1405.
   PubMed Web of Science ®Google Scholar
• Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350(9):876–885.
   PubMed Web of Science ®Google Scholar
• Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65.
   PubMed Web of Science ®Google Scholar
• Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323–333; quiz 591.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829–838.
   PubMed Web of Science ®Google Scholar
• Schreiber S, Lawrance IC, Thomsen OO, et al. Randomised clinical trial: certolizumab pegol for fistulas in Crohn’s disease - subgroup results from a placebo-controlled study. Aliment Pharmacol Ther. 2011;33(2):185–193.
   PubMed Web of Science ®Google Scholar
• Sands BE, Blank MA, Patel K, et al. Long-term treatment of rectovaginal fistulas in Crohn’s disease: response to infliximab in the ACCENT II Study. Clin Gastroenterol Hepatol. 2004;2(10):912–920.
   PubMed Web of Science ®Google Scholar
• Bouguen G, Siproudhis L, Gizard E, et al. Long-term outcome of perianal fistulizing Crohn’s disease treated with infliximab. Clin Gastroenterol Hepatol. 2013;11(8):975–81 e1-4.
   PubMed Web of Science ®Google Scholar
• Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–1395.
   PubMed Web of Science ®Google Scholar
• Feagan BG, Schwartz D, Danese S, et al. Efficacy of vedolizumab in fistulising Crohn’s disease: exploratory analyses of data from GEMINI 2. J Crohns Colitis. 2018;12(5):621–626.
   PubMed Web of Science ®Google Scholar
• Sands B, Gasink C, Sandborn WJ Fistula healing in pivotal studies of ustekinumab in Crohn’s disease. Gastroenterology. 2017;152 (5)(S185).
   Web of Science ®Google Scholar
• Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375(20):1946–1960.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012;367(16):1519–1528.
   PubMed Web of Science ®Google Scholar
• Regueiro M, Mardini H Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis. 2003;9(2):98–103.
   PubMed Web of Science ®Google Scholar
• Tanaka S, Matsuo K, Sasaki T, et al. Clinical advantages of combined seton placement and infliximab maintenance therapy for perianal fistulizing Crohn’s disease: when and how were the seton drains removed? Hepatogastroenterology. 2010;57(97):3–7.
   PubMedGoogle Scholar
• Hyder SA, Travis SP, Jewell DP, et al. Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum. 2006;49(12):1837–1841.
   PubMed Web of Science ®Google Scholar
• Davies M, Harris D, Lohana P, et al. The surgical management of fistula-in-ano in a specialist colorectal unit. Int J Colorectal Dis. 2008;23(9):833–838.
   PubMed Web of Science ®Google Scholar
• Soltani A, Kaiser AM Endorectal advancement flap for cryptoglandular or Crohn’s fistula-in-ano. Dis Colon Rectum. 2010;53(4):486–495.
   PubMed Web of Science ®Google Scholar
• Ellis CN, Rostas JW, Greiner FG Long-term outcomes with the use of bioprosthetic plugs for the management of complex anal fistulas. Dis Colon Rectum. 2010;53(5):798–802.
   PubMed Web of Science ®Google Scholar
• Owen G, Keshava A, Stewart P, et al. Plugs unplugged. Anal fistula plug: the Concord experience. ANZ J Surg. 2010;80(5):341–343.
   PubMed Web of Science ®Google Scholar
• Abcarian AM, Estrada JJ, Park J, et al. Ligation of intersphincteric fistula tract: early results of a pilot study. Dis Colon Rectum. 2012;55(7):778–782.
   PubMed Web of Science ®Google Scholar
• Cirocchi R, Santoro A, Trastulli S, et al. Meta-analysis of fibrin glue versus surgery for treatment of fistula-in-ano. Ann Ital Chir. 2010;81(5):349–356.
   PubMed Web of Science ®Google Scholar
• Siegmund B, Feakins RM, Barmias G, et al. Results of the Fifth Scientific Workshop of the ECCO (II): pathophysiology of perianal fistulizing disease. J Crohns Colitis. 2016;10(4):377–386.
   PubMed Web of Science ®Google Scholar
• Panes J, Rimola J Perianal fistulizing Crohn’s disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol. 2017;14(11):652–664.
   PubMed Web of Science ®Google Scholar
• Bataille F, Klebl F, Rummele P, et al. Morphological characterisation of Crohn’s disease fistulae. Gut. 2004;53(9):1314–1321.
   PubMed Web of Science ®Google Scholar
• Scharl M, Frei S, Pesch T, et al. Interleukin-13 and transforming growth factor beta synergise in the pathogenesis of human intestinal fistulae. Gut. 2013;62(1):63–72.
   PubMed Web of Science ®Google Scholar
• West RL, Van der Woude CJ, Endtz HP, et al. Perianal fistulas in Crohn’s disease are predominantly colonized by skin flora: implications for antibiotic treatment? Dig Dis Sci. 2005;50(7):1260–1263.
   PubMed Web of Science ®Google Scholar
• van Onkelen RS, Mitalas LE, Gosselink MP, et al. Assessment of microbiota and peptidoglycan in perianal fistulas. Diagn Microbiol Infect Dis. 2013;75(1):50–54.
   PubMed Web of Science ®Google Scholar
• Tozer PJ, Rayment N, Hart AL, et al. What role do bacteria play in persisting fistula formation in idiopathic and Crohn’s anal fistula? Colorectal Dis. 2015;17(3):235–241.
   PubMed Web of Science ®Google Scholar
• Lovisa S, Genovese G, Danese S Role of epithelial-to-mesenchymal transition in inflammatory bowel disease. J Crohns Colitis. 2018.
   PubMed Web of Science ®Google Scholar
• Kirkegaard T, Hansen A, Bruun E, et al. Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn’s disease. Gut. 2004;53(5):701–709.
   PubMed Web of Science ®Google Scholar
• von Lampe B, Barthel B, Coupland SE, et al. Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut. 2000;47(1):63–73.
   PubMed Web of Science ®Google Scholar
• Strioga M, Viswanathan S, Darinskas A, et al. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012;21(14):2724–2752.
   PubMed Web of Science ®Google Scholar
• Moll G, Ignatowicz L, Catar R, et al. Different procoagulant activity of therapeutic mesenchymal stromal cells derived from bone marrow and placental decidua. Stem Cells Dev. 2015;24(19):2269–2279.
   PubMed Web of Science ®Google Scholar
• Kim Y, Kim H, Cho H, et al. Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia. Cell Physiol Biochem. 2007;20(6):867–876.
   PubMed Web of Science ®Google Scholar
• Kern S, Eichler H, Stoeve J, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294–1301.
   PubMed Web of Science ®Google Scholar
• Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem. 2006;99(5):1285–1297.
   PubMed Web of Science ®Google Scholar
• Nie Y, Lau C, Lie A, et al. Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2010;19(7):850–859.
   PubMed Web of Science ®Google Scholar
• Choudhery MS, Khan M, Mahmood R, et al. Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and anti-apoptosis capabilities. Cell Biol Int. 2012;36(8):747–753.
   PubMed Web of Science ®Google Scholar
• Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31(10):890–896.
   PubMed Web of Science ®Google Scholar
• Berglund AK, Fortier LA, Antczak DF, et al. Immunoprivileged no more: measuring the immunogenicity of allogeneic adult mesenchymal stem cells. Stem Cell Res Ther. 2017;8(1):288.
   PubMed Web of Science ®Google Scholar
• Devine SM, Cobbs C, Jennings M, et al. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood. 2003;101(8):2999–3001.
   PubMed Web of Science ®Google Scholar
• Iso Y, Spees JL, Serrano C, et al. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment. Biochem Biophys Res Commun. 2007;354(3):700–706.
   PubMed Web of Science ®Google Scholar
• Gnecchi M Paracrine mechanisms of mesenchymal stem cells in tissue repair. Mesenchymal stem cells: methods and protocols, Second Edition: Springer Nature; 2011.
   Google Scholar
• Yao Y, Huang J, Geng YJ, et al. Paracrine action of mesenchymal stem cells revealed by single cell gene profiling in infarcted murine hearts. Plos One. 2015;10(6).
   Web of Science ®Google Scholar
• Nauta AJ, Fibbe WE Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110(10):3499–3506.
   PubMed Web of Science ®Google Scholar
• Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1):367–372.
   PubMed Web of Science ®Google Scholar
• Di IM, Bl DP, Moretti L, et al. Mesenchymal Cells Recruit and Regulate T Regulatory Cells. Haematol-Hematol J. 2008;93:S120–S.
   PubMed Web of Science ®Google Scholar
• Vasandan AB, Jahnavi S, Shashank C, et al. Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE(2)-dependent mechanism. Sci Rep-Uk. 2016;6:38308.
   Web of Science ®Google Scholar
• Spees JL, Lee RH, Gregory CA Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther. 2016;7(1):125.
   PubMed Web of Science ®Google Scholar
• Panes J, Garcia-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. Lancet. 2016;388(10051):1281–1290.
   PubMed Web of Science ®Google Scholar
• Panes J, Garcia-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. Gastroenterology. 2018;154(5):1334–42 e4.
   PubMed Web of Science ®Google Scholar
• de la Portilla F, Alba F, Garcia-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. Int J Colorectal Dis. 2013;28(3):313–323.
   PubMed Web of Science ®Google Scholar
• 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. Gastroenterology. 2015;149(4):918–27 e6.
   PubMed Web of Science ®Google Scholar
• 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. Stem Cells. 2013;31(11):2575–2581.
   PubMed Web of Science ®Google Scholar
• Cho YB, Park KJ, Yoon SN, et al. Long-term results of adipose-derived stem cell therapy for the treatment of Crohn’s fistula. Stem Cells Transl Med. 2015;4(5):532–537.
   PubMed Web of Science ®Google Scholar
• 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. Dis Colon Rectum. 2009;52(1):79–86.
   PubMed Web of Science ®Google Scholar
• 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. Gastroenterology. 2017;153(1):59–62 e2.
   PubMed Web of Science ®Google Scholar
• 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. Dis Colon Rectum. 2018;61(5):629–640.
   PubMed Web of Science ®Google Scholar
• Nistico P, Bissell MJ, Radisky DC Epithelial-mesenchymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases. Cold Spring Harb Perspect Biol. 2012;4(2).
   PubMed Web of Science ®Google Scholar
• Frei SM, Pesch T, Lang S, et al. A role for tumor necrosis factor and bacterial antigens in the pathogenesis of Crohn’s disease-associated fistulae. Inflamm Bowel Dis. 2013;19(13):2878–2887.
   PubMed Web of Science ®Google Scholar
• 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. Cell Transplant. 2013;22(2):279–285.
   PubMed Web of Science ®Google Scholar
• Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease. Gut. 2011;60(6):788–798.
   PubMed Web of Science ®Google Scholar
• 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. Mayo Clin Proc. 2015;90(6):747–755.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ. AGA technical review on perianal Crohn’s disease. Gastroenterology. 2003;125, 1508–1530.
   PubMed Web of Science ®Google Scholar