Клеточная терапия перианальных проявлений болезни Крона
Клеточная терапия перианальных проявлений болезни Крона
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Аннотация
Цель. Сравнить влияние комбинированной (местное и системное введение) терапии мезенхимальными стромальными клетками (МСК) костного мозга, антицитокиновой (инфликсимаб – ИФЛ) терапии и терапии антибиотиками (АБ) и иммуносупрессорами (ИС) на заживление простых перианальных свищей при болезни Крона (БК).
Материалы и методы. Первая группа больных БК в возрасте от 19 до 58 лет (Ме – 29; n=12) получала культуру МСК системно по схеме и местно. Вторая группа (n=10) от 20 до 68 лет (Ме – 36) получала ИФЛ по схеме. Третья группа (n=14) от 20 до 62 лет (Ме – 28) получала АБ и ИС. Эффективность оценивали по индексу активности БК, индексу перианальной активности БК и частоте рецидивов.
Результаты. Через 12 нед среди больных 1-й группы заживление простых свищей отмечено у 8 (66,6%) больных, во 2-й группе – у 6 (60%), в 3-й группе – у 1 (7,14%) пациента. Через 6 мес в 1-й группе больных заживление простых свищей сохранялось у 8 (66,6%), во 2-й группе – у 6 (60%), в 3-й группе – у 1 (7,14%) пациента. Через 12 мес в 1-й группе заживление сохранялось у 7 (58,3%), во 2-й группе – у 6 (60%), в 3-й группе – у 2 (14,3%) пациентов. Через 24 мес среди больных 1-й группы закрытие свищей сохранялось у 5 (41,6%) больных, во 2-й группе – у 4 (40%), в 3-й группе – у 0 (0%).
Заключение. Комбинированная клеточная и антицитокиновая терапия БК с перианальными поражениями достоверно способствует более частому и длительному закрытию простых свищей по сравнению с АБ/ИС, а также уменьшению частоты рецидивов заболевания.
Ключевые слова: болезнь Крона, свищевая форма, инфликсимаб, мезенхимальные стромальные клетки, клеточная терапия.
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.
Keywords: Crohn's disease, infliximab, fistula form, mesenchymal stromal cells, stem cell therapy.
Материалы и методы. Первая группа больных БК в возрасте от 19 до 58 лет (Ме – 29; n=12) получала культуру МСК системно по схеме и местно. Вторая группа (n=10) от 20 до 68 лет (Ме – 36) получала ИФЛ по схеме. Третья группа (n=14) от 20 до 62 лет (Ме – 28) получала АБ и ИС. Эффективность оценивали по индексу активности БК, индексу перианальной активности БК и частоте рецидивов.
Результаты. Через 12 нед среди больных 1-й группы заживление простых свищей отмечено у 8 (66,6%) больных, во 2-й группе – у 6 (60%), в 3-й группе – у 1 (7,14%) пациента. Через 6 мес в 1-й группе больных заживление простых свищей сохранялось у 8 (66,6%), во 2-й группе – у 6 (60%), в 3-й группе – у 1 (7,14%) пациента. Через 12 мес в 1-й группе заживление сохранялось у 7 (58,3%), во 2-й группе – у 6 (60%), в 3-й группе – у 2 (14,3%) пациентов. Через 24 мес среди больных 1-й группы закрытие свищей сохранялось у 5 (41,6%) больных, во 2-й группе – у 4 (40%), в 3-й группе – у 0 (0%).
Заключение. Комбинированная клеточная и антицитокиновая терапия БК с перианальными поражениями достоверно способствует более частому и длительному закрытию простых свищей по сравнению с АБ/ИС, а также уменьшению частоты рецидивов заболевания.
Ключевые слова: болезнь Крона, свищевая форма, инфликсимаб, мезенхимальные стромальные клетки, клеточная терапия.
________________________________________________
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.
Keywords: Crohn's disease, infliximab, fistula form, mesenchymal stromal cells, stem cell therapy.
Список литературы
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17. 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 Jan 21. Epub ahead of print.
18. 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. 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 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.
21. Gonzalez-Rey E, Anderson P, González MA, 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 ME, Welling MM 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. [Clinical guidelines for the diagnosis and treatment of adult patients with chronic paraproctitis (fistulas of the anus, fistula of the rectum). Russian public organization «Association of Coloproctology Russia», Moscow, 2013: 20. (In Russ.)]
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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. [Knyazev OV, Parfenov AI, Shcherbakov PL, Konoplyannikov AG, Ruchkina IN, Lishchinskaya AA. Combined biological therapy of the fistula form of Crohn's disease. Clinical demonstration. Therapeutic archive. 2014; 86 (2): 102-105. (In Russ.)]
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.
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 IC, Yarn MH, 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 BC, Lichtenstein GR 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 IC, 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 JO 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 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.
11. Tang LY, Rawsthorne P, Bernstein CN. 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 GR, 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 WJ, Fazio VW, Feagan BC et al. American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn's disease. Gastroenterology. 2003; 125: 1508-1530.
14. Williamson PR, Hollinger MD, Larch SW et al. Twenty year review of the surgical management of perianal Crohn’s disease. Dis Colon Rectum. 1995; 38: 389-92.
15.[Knyazev OV, Parfenov AI, Shcherbakov PL., Ruchkina IN, Konoplyannikov AG. Cell therapy for refractory Crohn's disease. Cell technologies in biology and medicine. 2013; 3: 145-152. (In Russ.)]
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 ME, 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 JA. 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 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.
21. Gonzalez-Rey E, Anderson P, González MA, 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 ME, Welling MM 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. [Clinical guidelines for the diagnosis and treatment of adult patients with chronic paraproctitis (fistulas of the anus, fistula of the rectum). Russian public organization «Association of Coloproctology Russia», Moscow, 2013: 20. (In Russ.)]
27. [Tsyb AF, Konoplyannikov AG, Kolesnikov AI, Pavlov VV. The preparation and use in medicine, cell cultures of mesenchymal stem cells of bone marrow. Bulletin of the Russian Academy of Medical Sciences. 2004; 59 (9): 71-76. (In Russ.)]
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. Knyazev OV, Parfenov AI, Shcherbakov PL, Konoplyannikov AG, Ruchkina IN, Lishchinskaya AA. Combined biological therapy of the fistula form of Crohn's disease. Clinical demonstration. Therapeutic archive. 2014; 86 (2): 102-105. (In Russ.)]
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.
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 IC, Yarn MH, 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 BC, Lichtenstein GR 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 IC, 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 JO 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 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.
11. Tang LY, Rawsthorne P, Bernstein CN. 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 GR, 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 WJ, Fazio VW, Feagan BC et al. American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn's disease. Gastroenterology. 2003; 125: 1508-1530.
14. Williamson PR, Hollinger MD, Larch SW 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. [Knyazev OV, Parfenov AI, Shcherbakov PL., Ruchkina IN, Konoplyannikov AG. Cell therapy for refractory Crohn's disease. Cell technologies in biology and medicine. 2013; 3: 145-152. (In Russ.)]
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 ME, 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 JA. 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 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.
21. Gonzalez-Rey E, Anderson P, González MA, 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 ME, Welling MM 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. [Clinical guidelines for the diagnosis and treatment of adult patients with chronic paraproctitis (fistulas of the anus, fistula of the rectum). Russian public organization «Association of Coloproctology Russia», Moscow, 2013: 20. (In Russ.)]
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. [Tsyb AF, Konoplyannikov AG, Kolesnikov AI, Pavlov VV. The preparation and use in medicine, cell cultures of mesenchymal stem cells of bone marrow. Bulletin of the Russian Academy of Medical Sciences. 2004; 59 (9): 71-76. (In Russ.)]
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. [Knyazev OV, Parfenov AI, Shcherbakov PL, Konoplyannikov AG, Ruchkina IN, Lishchinskaya AA. Combined biological therapy of the fistula form of Crohn's disease. Clinical demonstration. Therapeutic archive. 2014; 86 (2): 102-105. (In Russ.)]
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.
________________________________________________
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 IC, Yarn MH, 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 BC, Lichtenstein GR 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 IC, 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 JO 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 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.
11. Tang LY, Rawsthorne P, Bernstein CN. 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 GR, 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 WJ, Fazio VW, Feagan BC et al. American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn's disease. Gastroenterology. 2003; 125: 1508-1530.
14. Williamson PR, Hollinger MD, Larch SW et al. Twenty year review of the surgical management of perianal Crohn’s disease. Dis Colon Rectum. 1995; 38: 389-92.
15.[Knyazev OV, Parfenov AI, Shcherbakov PL., Ruchkina IN, Konoplyannikov AG. Cell therapy for refractory Crohn's disease. Cell technologies in biology and medicine. 2013; 3: 145-152. (In Russ.)]
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 ME, 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 JA. 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 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.
21. Gonzalez-Rey E, Anderson P, González MA, 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 ME, Welling MM 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. [Clinical guidelines for the diagnosis and treatment of adult patients with chronic paraproctitis (fistulas of the anus, fistula of the rectum). Russian public organization «Association of Coloproctology Russia», Moscow, 2013: 20. (In Russ.)]
27. [Tsyb AF, Konoplyannikov AG, Kolesnikov AI, Pavlov VV. The preparation and use in medicine, cell cultures of mesenchymal stem cells of bone marrow. Bulletin of the Russian Academy of Medical Sciences. 2004; 59 (9): 71-76. (In Russ.)]
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. Knyazev OV, Parfenov AI, Shcherbakov PL, Konoplyannikov AG, Ruchkina IN, Lishchinskaya AA. Combined biological therapy of the fistula form of Crohn's disease. Clinical demonstration. Therapeutic archive. 2014; 86 (2): 102-105. (In Russ.)]
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.
Авторы
О.В. КНЯЗЕВ 1, Н.А. ФАДЕЕВА 1, А.В. КАГРАМАНОВА 1, Н.И. БЕЛЯКОВ 1, Н.В. ОРЛОВА 1, А.А. ЛИЩИНСКАЯ 1, А.Г. КОНОПЛЯННИКОВ 2, А.И. ПАРФЕНОВ 1
1 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова Департамента здравоохранения г. Москвы», Москва, Россия;
2 Медицинский радиологический научный центр им. А.Ф. Цыба Минздрава РФ, Обнинск, Россия
1 Moscow Clinical Research Center, Moscow, Russia;
2Medical Radiological Research Center, Obninsk, Russia
1 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова Департамента здравоохранения г. Москвы», Москва, Россия;
2 Медицинский радиологический научный центр им. А.Ф. Цыба Минздрава РФ, Обнинск, Россия
________________________________________________
1 Moscow Clinical Research Center, Moscow, Russia;
2Medical Radiological Research Center, Obninsk, Russia
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