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MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ

Year 2011, Volume: 74 Issue: 4, 59 - 63, 08.02.2012

Abstract

Amaç: Mezenkimal kök hücreler (MKH) T hücre oluşumunu ve antijen sunan hücreleri inhibe ederek inflamatuar sitokinlerin
salınımını baskılayarak (IFN-γ, TNF-α) ve antiinflamatuar sitokinlerin (IL-10) salınımını arttırarak immunsupresiv etki
oluşturmaktadırlar. Crohn hastalığında bağırsaklarda oluşan mukozal hasarda ise birçok sitokin sorumlu olmakla birlikte TNF-α
bunlar içerisinde önde gelenlerdendir. Bu çalışmanın amacı MKH lerin Deneysel Kolit modelinde tedavideki yerini belirlemektir.
Gereç ve yöntem: Deneysel kolit oluşturmak için %3 Dekstran sülfat sodyum (DSS) kulllanıldı. Çalışma her grup da 6 sar rat
olmak üzere 7 grup üzerinde yapıldı: Grup 1:SHAM grubu, Grup 2: DSS+ placebo, Grup 3: DSS+ metilprednisolon 1 mg/kg, po,
Grup 4: DSS + mesalazin 100 mg/kg, po., Grup 5: DSS+ MKH,106 hücre/rat, intraperitoneal, Grup 6: DSS + metilprednisolon 1
mg/kg, po + MKH,106 hücre/rat, intraperitoneal, Grup 7: DSS + mesalazin 100 mg/kg, po + MKH, 106 hücre/rat, intraperitoneal.
Gruplar patolojik ve biyokimyasal (TNF, INF IL-10) parametrelerdeki değişimler ölçülerek karşılaştırıldı.
Bulgular: Patolojik değerlendirmede Grup 1, 2 ve 3‘ün ortalama skorlarının Grup 5, 6 ve 7‘nin ortalama skorlarından belirgin
yüksek olduğu gözlendi (p < 0,05). IL-10 düzeyi Grup 1 için 108,33±2,23 pg/ml, Grup 2 için 80,83±3,62 pg/ml olup MKH tedavisi
verilen gruplar olan Grup 5, 6 ve 7 de bu değerler sırasıyla 131,66±3,83 pg/ml, 138,33±3,19 pg/ml ve 115,33±5,21 pg/ml olarak
ölçülmüş olup, bu son üç grup ortalamalarının anlamlı olarak yüksek olduğu gözlendi (p < 0,05). IFN-γ ve TNF-α düzeyleri
açısından gruplar arasında anlamlı bir fark bulunmadı.
Sonuç: Bu çalışmanın sonucuna göre MKH‘in IL-10 düzeyini yükselterek Crohn hastalığı tedavisinde yeri olabileceği
düşünülebilir.

References

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  • Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human firsttrimester fetal blood, liver, and bone marrow. Blood 2001; 98: 2396-2402
  • Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-650.
  • Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid expansion of recycling stem cells in cultures of plasticadherent cells from human bone marrow. Proc Natl Acad Sci USA 2000; 97: 3213-3218.
  • Derkx B, Taminiau J, Radema S, Stronkhorst A, Wortel C, Tytgat G, van Deventer S. Tumour necrosis factor antibody treatment in Crohn's disease. Lancet 1993; 342:173-174.
  • Devine SM, Cobbs C Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusions into nonhuman primates. Blood 2003; 101: 2009-3001.
  • Fedorak RW, Empley LR, Walker K. Verapamil alters eicosanoid synthesis and accelerates healing during experimental colitis in rats. Gastroenterology 1992; 102: 1229-1235.
  • González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by ınhibiting ınflammatory and autoimmune responses. Gastroenterology 2009; 136: 978-989.
  • 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: 929-939.
  • Helm GA, Gazit Z. Future uses of mesenchymal stem cells in spine surgery. Neurosurg Focus 2005; 19:E13.
  • Irvine EJ, Farrokhyar F, Swarbrick ET. A critical review of epidemiological studies in inflammatory bowel disease. Scand J Gastroenterol 2001; 36: 2-15.
  • Kemp KC, Hows J, Donaldson C. Bonemarrow-derived mesenchymal stem cells. Leuk Lymphoma 2005; 46: 1531- 1544.
  • Krabbe C, Zimmer J, Meyer M. Neural transdifferentiation of mesenchymal stem cells-a critical review. APMIS 2005; 113:831-844.
  • Le Blanc K, Rıngden O. Immunomodulation by mesenchymal stem cells and clinical experience. Journal of Internal Medicine 2007; 262: 509-525.
  • MacDermott RP. Progress in understanding the mechanisms of action of 5- aminosalicylic acid. Am J Gastroenterol 2000; 95: 3343-3345.
  • Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: A prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut 1989; 30: 983-989.
  • Misiewicz JJ, Lond MB. Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet 1965; 2: 185.
  • Moore KL. The developing human: Clinically oriented embriology. In: Moore KL (ed). The Developing Human.WB Saunders, Philadelphia, London, 4th ed. ,1988.
  • Munkholm P, Langholz E, Davidsen M, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn's disease. Gut 1994; 35: 360-362.
  • Munkholm P. Crohn's disease—occurrence, course and prognosis: An epidemiologic cohort-study. Dan Med Bull 1997; 44: 287-302.
  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
  • Rao MS, Mattson MP. Stem cells and aging: expanding the possibilities. Mech Ageing Dev 2001; 122: 713-734.
  • Sands BE. Crohn‘s Disease. In: Feldman M. (ed). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8 th ed. Saunders, 2006: pp 2459-2498.
  • Sands BE. Novel therapies for inflammatory bowel disease. Gastroenterol Clin North Am 1999; 28: 323- 351.
  • Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: A randomized study. N Engl J Med 1987; 317: 1625-1629.
  • Scotiniotis I, Rubesin SE, Ginsberg GG. Imaging modalities in inflammatory bowel disease. Gastroenterol Clin North Am 1999; 28:391-421.
  • Su C, Lichtenstein GR. Ulcerative Colitis. In: Feldman M (ed). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed. Saunders, 2006: pp 2499-2548.
  • Truelove SC, Witts LJ. Cortisone in ulcerative colitis: Final report on a therapeutic trial. BMJ 1955; 2: 1041-1048.
  • Uccelli A, Zappia E, Benvenuto F, Frassoni F, Mancardi G. Stem cells in inflammatory demyelinating disorders: a dual role for immunosuppression and neuroprotection. Expert Opin Biol Ther 2006; 6:17-22.
Year 2011, Volume: 74 Issue: 4, 59 - 63, 08.02.2012

Abstract

References

  • Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stem cells: Nature, biology, and potential applications. Stem Cells 2001; 19: 180- 192.
  • Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human firsttrimester fetal blood, liver, and bone marrow. Blood 2001; 98: 2396-2402
  • Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-650.
  • Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid expansion of recycling stem cells in cultures of plasticadherent cells from human bone marrow. Proc Natl Acad Sci USA 2000; 97: 3213-3218.
  • Derkx B, Taminiau J, Radema S, Stronkhorst A, Wortel C, Tytgat G, van Deventer S. Tumour necrosis factor antibody treatment in Crohn's disease. Lancet 1993; 342:173-174.
  • Devine SM, Cobbs C Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusions into nonhuman primates. Blood 2003; 101: 2009-3001.
  • Fedorak RW, Empley LR, Walker K. Verapamil alters eicosanoid synthesis and accelerates healing during experimental colitis in rats. Gastroenterology 1992; 102: 1229-1235.
  • González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by ınhibiting ınflammatory and autoimmune responses. Gastroenterology 2009; 136: 978-989.
  • 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: 929-939.
  • Helm GA, Gazit Z. Future uses of mesenchymal stem cells in spine surgery. Neurosurg Focus 2005; 19:E13.
  • Irvine EJ, Farrokhyar F, Swarbrick ET. A critical review of epidemiological studies in inflammatory bowel disease. Scand J Gastroenterol 2001; 36: 2-15.
  • Kemp KC, Hows J, Donaldson C. Bonemarrow-derived mesenchymal stem cells. Leuk Lymphoma 2005; 46: 1531- 1544.
  • Krabbe C, Zimmer J, Meyer M. Neural transdifferentiation of mesenchymal stem cells-a critical review. APMIS 2005; 113:831-844.
  • Le Blanc K, Rıngden O. Immunomodulation by mesenchymal stem cells and clinical experience. Journal of Internal Medicine 2007; 262: 509-525.
  • MacDermott RP. Progress in understanding the mechanisms of action of 5- aminosalicylic acid. Am J Gastroenterol 2000; 95: 3343-3345.
  • Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: A prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut 1989; 30: 983-989.
  • Misiewicz JJ, Lond MB. Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet 1965; 2: 185.
  • Moore KL. The developing human: Clinically oriented embriology. In: Moore KL (ed). The Developing Human.WB Saunders, Philadelphia, London, 4th ed. ,1988.
  • Munkholm P, Langholz E, Davidsen M, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn's disease. Gut 1994; 35: 360-362.
  • Munkholm P. Crohn's disease—occurrence, course and prognosis: An epidemiologic cohort-study. Dan Med Bull 1997; 44: 287-302.
  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
  • Rao MS, Mattson MP. Stem cells and aging: expanding the possibilities. Mech Ageing Dev 2001; 122: 713-734.
  • Sands BE. Crohn‘s Disease. In: Feldman M. (ed). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8 th ed. Saunders, 2006: pp 2459-2498.
  • Sands BE. Novel therapies for inflammatory bowel disease. Gastroenterol Clin North Am 1999; 28: 323- 351.
  • Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: A randomized study. N Engl J Med 1987; 317: 1625-1629.
  • Scotiniotis I, Rubesin SE, Ginsberg GG. Imaging modalities in inflammatory bowel disease. Gastroenterol Clin North Am 1999; 28:391-421.
  • Su C, Lichtenstein GR. Ulcerative Colitis. In: Feldman M (ed). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed. Saunders, 2006: pp 2499-2548.
  • Truelove SC, Witts LJ. Cortisone in ulcerative colitis: Final report on a therapeutic trial. BMJ 1955; 2: 1041-1048.
  • Uccelli A, Zappia E, Benvenuto F, Frassoni F, Mancardi G. Stem cells in inflammatory demyelinating disorders: a dual role for immunosuppression and neuroprotection. Expert Opin Biol Ther 2006; 6:17-22.
There are 29 citations in total.

Details

Primary Language Turkish
Journal Section Clinical Research
Authors

İbrahim Şenkal This is me

Ümit Akyüz This is me

Fırat Yalnız This is me

Ferda Çiftçi This is me

Aysel Yurtsever This is me

Cengiz Pata This is me

Publication Date February 8, 2012
Submission Date February 8, 2012
Published in Issue Year 2011 Volume: 74 Issue: 4

Cite

APA Şenkal, İ., Akyüz, Ü., Yalnız, F., Çiftçi, F., et al. (2012). MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ. Journal of Istanbul Faculty of Medicine, 74(4), 59-63.
AMA Şenkal İ, Akyüz Ü, Yalnız F, Çiftçi F, Yurtsever A, Pata C. MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ. İst Tıp Fak Derg. February 2012;74(4):59-63.
Chicago Şenkal, İbrahim, Ümit Akyüz, Fırat Yalnız, Ferda Çiftçi, Aysel Yurtsever, and Cengiz Pata. “MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ”. Journal of Istanbul Faculty of Medicine 74, no. 4 (February 2012): 59-63.
EndNote Şenkal İ, Akyüz Ü, Yalnız F, Çiftçi F, Yurtsever A, Pata C (February 1, 2012) MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ. Journal of Istanbul Faculty of Medicine 74 4 59–63.
IEEE İ. Şenkal, Ü. Akyüz, F. Yalnız, F. Çiftçi, A. Yurtsever, and C. Pata, “MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ”, İst Tıp Fak Derg, vol. 74, no. 4, pp. 59–63, 2012.
ISNAD Şenkal, İbrahim et al. “MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ”. Journal of Istanbul Faculty of Medicine 74/4 (February 2012), 59-63.
JAMA Şenkal İ, Akyüz Ü, Yalnız F, Çiftçi F, Yurtsever A, Pata C. MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ. İst Tıp Fak Derg. 2012;74:59–63.
MLA Şenkal, İbrahim et al. “MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ”. Journal of Istanbul Faculty of Medicine, vol. 74, no. 4, 2012, pp. 59-63.
Vancouver Şenkal İ, Akyüz Ü, Yalnız F, Çiftçi F, Yurtsever A, Pata C. MEZENKİMAL KÖK HÜCRELERİN RATLARDA CROHN HASTALIĞI MODELİNDE DOKU HASARI, İNFLAMATUAR VE ANTİNFLAMATUAR SİTOKİNLERE ETKİSİ. İst Tıp Fak Derg. 2012;74(4):59-63.

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Email: itfdergisi@istanbul.edu.tr

Phone: +90 212 414 21 61