title: Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients.
abstract: BACKGROUND
  In 2003, we initiated a clinical trial to examine autologous bone marrow cell infusion (ABMi) therapy for cirrhotic patients and reported the clinical effect of the therapy. To analyze how splenectomy may potentiate the effects of bone marrow cell infusion on cirrhosis, we performed a mouse study and a clinical trial on patients with cirrhosis.
  
  
  METHODS
  In mice, we analyzed the effect of splenectomy on bone marrow cell infusion in four experimental groups (group A, splenectomy + bone marrow cell infusion + CCl(4); group B, sham operation + bone marrow cell infusion + CCl(4); group C, splenectomy + CCl(4); group D, sham operation + CCl(4)). In clinical, we compared the effect of splenectomy on ABMi therapy.
  
  
  RESULTS
  We observed significantly increased average serum albumin levels and higher expression of green fluorescent protein (GFP), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen in the livers of group A. We observed MMP9/GFP double-positive cells in the cirrhotic livers. A significant decrease in the liver fibrosis areas was observed in group A. Splenectomy enhanced the repopulation of bone marrow cells into the cirrhotic liver and improved the liver microenvironment via expression of MMP9 secreted from repopulating GFP-positive cells. Next, we performed a clinical trial to compare the effect of splenectomy on the efficacy of ABMi therapy. Cirrhotic patients who underwent splenectomy before ABMi therapy tended to have a greater improvement in liver function.
  
  
  CONCLUSIONS
  ABMi therapy with splenectomy may be an effective therapeutic modality for cirrhosis.
authors: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
authors: Takuya
authors: T
authors: Iwamoto
authors: Shuji
authors: S
authors: Terai
authors: Yuko
authors: Y
authors: Mizunaga
authors: Naoki
authors: N
authors: Yamamoto
authors: Kaoru
authors: K
authors: Omori
authors: Koichi
authors: K
authors: Uchida
authors: Takahiro
authors: T
authors: Yamasaki
authors: Yasuhiko
authors: Y
authors: Fujii
authors: Hiroshi
authors: H
authors: Nishina
authors: Isao
authors: I
authors: Sakaida
mesh_terms: D000368:Aged; D000818:Animals; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000628:therapy*; D008106:Liver Cirrhosis, Experimental / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism; D013156:Splenectomy / Q000379:methods*
chemical_list: D012709:Serum Albumin; D020780:Matrix Metalloproteinase 9