USE of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases

Leonid Borisovich Lazebnik; Лазебник Леонид Борисович; Anatoliy Georgievich Konoplyannikov; Коноплянников Анатолий Георгиевич; Oleg Vladimirovich Knyazev; Князев Олег Владимирович; Asfol'd Ivanovich Parfenov; Парфенов Асфольд Иванович; Tamara Mikhaylovna Tsaregorodtseva; Царегородцева Тамара Михайловна; Irina Nikolaevna Ruchkina; Ручкина Ирина Николаевна; Sergey Germanovich Khomeriki; Хомерики Сергей Германович; Vera Aleksandrovna Rogozina; Рогозина Вера Александровна; Ol'ga Andreevna Konoplyannikova; Коноплянникова Ольга Андреевна; L B Lazebnik; Lazebnik L B; A G Konoplyannikov; Konoplyannikov A G; O V Knyazev; Knyazev O V; A I Parfenov; Parfenov A I; T M Tsaregorodtseva; Tsaregorodtseva T M; I N Ruchkina; Ruchkina I N; S G Khomeriki; Khomeriki S G; V A Rogozina; Rogozina V A; O A Konoplyannikova; Konoplyannikova O A

USE of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases

Authors: Lazebnik L.B.¹, Konoplyannikov A.G.², Knyazev O.V.¹, Parfenov A.I.¹, Tsaregorodtseva T.M.¹, Ruchkina I.N.¹, Khomeriki S.G.¹, Rogozina V.A.¹, Konoplyannikova O.A.², Lazebnik LB², Konoplyannikov AG², Knyazev OV², Parfenov AI², Tsaregorodtseva TM², Ruchkina IN², Khomeriki SG², Rogozina VA², Konoplyannikova OA²
Affiliations:
1. Центральный научно-исследовательский институт гастроэнтерологии Департамента здравоохранения Москвы
2. Медицинский радиологический научный центр РАМН
Issue: Vol 82, No 2 (2010)
Pages: 38-43
Section: Editorial
URL: https://journals.rcsi.science/0040-3660/article/view/30543
ID: 30543

Cite item

Abstract

Aim. to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chronic intestinal inflammatory diseases (IID).
Subjects and methods. Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn's disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn's disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2)108 cells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion.
Results. A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comparison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only.
Conclusion. The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

Keywords

allogeneic mesenchymal stem cells, Crohn's disease, ulcerative colitis

References

Fiocchi С. The multifactorial pathogenesis of IBD. Jn: Inflammatory bowel disease - diagnostic and therapeutic strategies: Falk symposium 154. June 9-10. Abstracts. 2006: 21-22.
Frieedenstein A. J., Petrakova K. V., Kurolesova A. L., Frolova G. P. Hetrotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoetic tissue. Transplantation 1968; 6 (2): 230-247.
Dennis J., Charbord P. Origin and differentiation of human and murine stroma stem. Cells 2002; 20: 205-214.
Stasi R., Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin. Proc. 2004; 79 (4): 504-522.
Aggarwal S., Pittinger M. F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105 (4): 1815-1822.
Makino S., Fukuda K., Mioshi S. et al. Cardiomyocytes can be regeneration from marrow stromal cells in vitro. J. Clin. Invest. 1999; 103: 697-705.
Шахов В. П., Кокарев О. В., Попов С. В. и др. Феномен формирования мезенхимальных островков из клеток костного мозга мышей в системе in vitro. Бюл. сиб. мед. 2004; 1: 60-62.
Шумаков В. И., Казаков Э. Н., Онищенко H. A. и др. Первый опыт клинического применения аутологичных мезенхимальных стволовых клеток костного мозга для восстановления сократительной функции миокарда. Рос. кардиол. журн. 2003; 5: 42-50.
Caplan A. I., Heckman J. D., Lennon D. P. et al. Osteochondral progenitor cells in acute and chronic canine nonunions. J. Orthop. Res. 1999; 17: 246-255.
Tyndall A., Matucci-Cerinic M. Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders. Expert Opin. Biol. Ther. 2003; 3 (7): 1040-1049.
Jayne D., Passweg J., Marmont A. et al. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus 2004; 13 (3): 168-176.
Chaudhari M., Cornelius J. G., Schatz D. et al. Pancreatic stem cells: a therapeutic agent that may offer the best approach for curing type 1 diabetes. Pediatr Diabet. 2001; 2 (4): 195-202.
Yamaoka Т. Regeneration therapy of pancreatic beta cells: towards a cure for diabetes? Biochem. Biophys. Res. Commun. 2002; 296 (5): 1039-1043.
Васильева И. А., Коноплянников А. Г., Ерохин В. В. и др. Лечебный эффект системной трансплантации культивируемых аутогенных мезенхимальных стволовых клеток костного мозга у больных с резистентными формами туберкулеза легких. Клеточ. трансплантол. 2007; 1: 77-80.
Манукян Г. В., Ерамишанцев А. К., Сухих Г. Т. и др. Трансплантация фетальных клеток в лечении больных циррозом печени и портальной гипертензией. Гепатология 2004; 6: 14-20.
Черных Е. П., Пальцев А. И., Старостина Н. М. и др. Аутологичные клетки костного мозга в комплексном лечении пациентов хроническими гепатитами и циррозом печени. Гепатология 2005; 1: 30-36.
Banias G., Sugawara K., Pagnini С., Cominelli F. The Thl immune pathway as a therapeutic target in Crohn's disease. Curr. Opin. Invest. Drugs 2003; 4: 1279-1286.
Hugot J. P., Chamaillard M., Zouali H. et al. Association of NOD2 lencinerich repeat variants with susceptibility to Crohn's disease. Nature 2001; 411: 599-603.
Oyama Y., Craig R. M., Traynor A. E. et al. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. Gastroenterology 2005; 128 (3): 552-563.
Hawkey C. J. Stem cell transplantation for Crohn's disease. Best Pract. Res. Clin. Haematol. 2004; 17 (2): 317-325.
Geboes K., Riddel R., Jensfelt B. et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 2000; 47: 404-409.
Цыб А. Ф., Коноплянников А. Г., Колесникова А. И. и др. Получение и использование в медицине клеточных культур из мезенхимальных стволовых клеток костного мозга человека. Вестн. РАМН. 2004; 59 (9): 71-76.

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USE of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases

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