Stem Cell Therapy for Perianal Crohn’s Disease


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Abstract

Aim. To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease. Materials and methods. In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses. Results. After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%). Conclusion. Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.

About the authors

O V Knyazev

Moscow Clinical Research Center

д.м.н., зав. отд-нием воспалительных заболеваний кишечника Moscow, Russia

N A Fadeeva

Moscow Clinical Research Center

к.м.н., с.н.с. отд-ния воспалительных заболеваний кишечника Moscow, Russia

A V Kagramanova

Moscow Clinical Research Center

к.м.н., с.н.с. отд-ния патологии кишечника Moscow, Russia

N I Belyakov

Moscow Clinical Research Center

ординатор отд-ния воспалительных заболеваний кишечника Moscow, Russia

N V Orlova

Moscow Clinical Research Center

зав. отд-нием рентгенологии Moscow, Russia

A A Lishchinskaya

Moscow Clinical Research Center

к.м.н., н.с. отд-ния воспалительных заболеваний кишечника Moscow, Russia

A G Konoplyannikov

Medical Radiological Research Center

проф., зав. отд-нием клеточной и экспериментальной лучевой терапии Obninsk, Russia

A I Parfenov

Moscow Clinical Research Center

Email: asfold@mail.ru
д.м.н., проф., зав. отделом патологии кишечника Moscow, Russia

References

  1. Sachar D.B, Andrew H.A, Farmer R.G el al. Proposed classification of patient subgroups in Crohn's disease. Gastroenterol Intern. 1992; 5: 141-154.
  2. Cosnes J, Cattan S, Blain A et al. Longterm evolution of disease behavior of Crohn's disease. Inflamm Bowel Dis. 2002; 8: 244-250.
  3. Solberg I.C, Yarn M.H, Hoie O et al. Clinical course in Crohn's disease: results of a Norwegian population - based ten - year follow - up study. Clin Gastroenterol Hepatol. 2007; 5: 1430-1438.
  4. Munkholm P, Langholz E, Davidsen M, Binder V. Disease activity courses in a regional cohort of Crohn's. Scand J Gastroenterol. 1995; 30: 699-706.
  5. Rutgeerts P, Feagan B.C, Lichtenstein G.R et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease. Gastroenterology. 2004; 126: 402-413.
  6. Schnitzler E, Fielder H, Ferrante M et al. Mucosal healing predicts long - term outcome for maintenance therapy with infliximab in Crohn's disease. Inflamm Bowel Dis. 2009; 15: 1295-1301.
  7. Solberg I.C, Lygren I, Jahnsen J et al. Mucosal healing after initial treatment may be a prognostic marker for long - term outcome in inflammatory bowel disease. Gut. 2008; 57 (Suppl. II): A-15.
  8. Dignass A, Van Assche G, Lindsay J.O et al. The second European evidencebased consensus on the diagnosis and management of Crohn's disease: current management. J Crohn's Colitis. 2010; 4: 28-62.
  9. Hellers G, Bergstrand O, Ewerth S, Holmstrom B. Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut. 1980; 21 (6): 525-7.
  10. Schwartz D.A, Loftus E.V. Jr., Tremaine W.J, Panaccione R, Harmsen W.S, Zinsmeister A.R et al. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002; 122 (4): 875-80.
  11. Tang L.Y, Rawsthorne P, Bernstein C.N. Are perineal and luminal fistulas associated in Crohn's disease? A population - based study. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association. 2006; 4 (9): 1130-4.
  12. Lichtenstein G.R, Van S, Bala M et al. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology. 2005; 128: 862-86.
  13. Sandborn W.J, Fazio V.W, Feagan B.C et al. American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn's disease. Gastroenterology. 2003; 125: 1508-1530.
  14. Williamson P.R, Hollinger M.D, Larch S.W et al. Twenty year review of the surgical management of perianal Crohn’s disease. Dis Colon Rectum. 1995; 38: 389-92.
  15. Князев О.В. Клеточная терапия рефрактерных форм болезни Крона / О. В. Князев, А.И. Парфенов, П.Л. Щербаков, И.Н. Ручкина, А.Г. Конопляников. Клеточные технологии в биологии и медицине. 2013; 3: 145-152.
  16. Aguilera-Castro L, Ferre-Aracil C, Garcia-Garcia - de-Paredes A, Rodriguez - de - Santiago E, Lopez-Sanroman A. Management of complex perianal Crohn's disease. Ann Gastroenterol. 2017; 30 (1): 33-44. doi: 10.20524/aog.2016.0099
  17. Ciccocioppo R, Bernardo M.E, Sgarella A et al. Autologous bone marrow - derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease. Gut. 2011 Jan 21. Epub ahead of print.
  18. García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes J.A. A phase I clinical trial of the treatment of crohn’s fistula by adipose mesenchymal stem cell transplantation. Diseases of the Colon and Rectum. 2005; 48 (7): 1416-1423.
  19. 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. Diseases of the Colon and Rectum. 2009; 52(1): 79-86.
  20. Ciccocioppo R, Bernardo M.E, 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.
  21. Gonzalez-Rey E, Anderson P, González M.A, Rico L, Büscher D, Delgado M. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut. 2009; 58 (7): 929-939.
  22. Duijvestein M, Wildenberg M.E, Welling M.M et al. Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis. Stem Cells. 2011; 29: 1549-1558.
  23. Lei Yea, Xiaowei Wua, Na Yua, Jingxin Panb, Lianming Liaoc, Fangyu. Clinical efficacy and safety of stem cells in refractory Crohn's disease: A systematic review. Wang Journal of Cellular Immunotherapy. March 2016; 2 (1): 21-2.
  24. Panes J. Stem Cell Therapy for Perianal Fistulas in Crohn's Disease. Gastroenterol Hepatol (NY). 2016 Oct; 12 (10): 637-640.
  25. Fernando de la Portilla, Ana M. García Cabrera, Rosa M. Rodríguez Jiménez, Maria L. Reyes and Damian García Olmo. Autologous and Allogeneic Stem Cell Transplantation for Treatment of Crohn’s Fistulae/New Insights into Inflammatory Bowel Disease. Edited by Samuel Huber, ISBN 978-953-51-2755-0, Print ISBN 978-953-51-2754-3, 262 pages, Publisher: InTech, Chapters published October 26. doi: 10.5772/61540
  26. Клинические рекомендации по диагностике и лечению взрослых больных хроническим парапроктитом (свищ заднего прохода, свищ прямой кишки). Общероссийская общественная организация «Ассоциация колопроктологов России», Москва, 2013: 20.
  27. Цыб А.Ф., Коноплянников А.Г., Колесникова А.И., Павлов В.В. Получение и использование в медицине клеточных культур из мезенхимальных стволовых клеток костного мозга человека. Вестник Российской Академии медицинских наук. 2004; 59 (9): 71-76.
  28. Friedenstein A, Chailakhyan R, Latsinik N, Panasyuk A, Keiliss-Borok I. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974; 17: 331-340.
  29. Zuk P, Zhu M, Ashjian P, De Ugarte D, Huang J, Mizuno H et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13: 4279-4295.
  30. Sensebe L, Krampera M, Schrezenmeier H, Bourin P, Giordano R. Mesenchymal stem cells for clinical application. Vox Sang. 2010; 98: 93-107.
  31. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, Mcintosh K, Patil S et al. (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 30: 42-48.
  32. Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E et al. Bone marrow mesenchymal stem cells inhibit the response of naïve and memory antigen - specific T cells to their cognate peptide. Blood. 2003; 101: 3722-3729.
  33. Stappenbeck T, Miyoshi H. The role of stromal stem cells in tissue regeneration and wound repair. Science. 2009; 324: 1666-166.
  34. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003; 31: 890-896.
  35. Augello A, Tasso R, Negrini S, Amateis A, Indiveri F, Cancedda R et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol. 2005; 35: 1482-1490.
  36. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni P, Matteucci P et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002; 99: 3838-3843.
  37. Ankrum J, Ong J, Karp J. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotech. 2014; 32: 252-260.
  38. Князев О.В., Парфенов А.И., Щербаков П.Л., Коноплянников А.Г., Ручкина И.Н., Лищинская А.А. Комбинированная биологическая терапия свищевой формы болезни Крона. Клиническая демонстрация. Терапевтический архив. 2014; 86 (2):102-105.
  39. Schwartz D, Loftus E, Tremaine W, Panaccione R, Harmsen W, Zinsmeister A et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology. 2002; 122: 875-880.

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