Development of cell therapy using autologous bone marrow cells for liver cirrhosis

被引:54
作者
Isao Sakaida
Shuji Terai
Hiroshi Nishina
Kiwamu Okita
机构
[1] Yamaguchi University School of Medicine,Department of Gastroenterology & Hepatology
[2] Tokyo Medical and Dental University,Department of Developmental and Regenerative Biology, Medical Research Institute
关键词
Bone marrow cell (BMC); Liver cirrhosis; GFP (green fluorescent protein); Liver fibrosis; Stem cell; Liv8;
D O I
10.1007/s00795-005-0298-z
中图分类号
学科分类号
摘要
The plasticity of bone marrow has been confirmed by the autopsy of a female recipient of bone marrow cell transplantation from a male donor. To establish new clinical cell therapies using autologous bone marrow cells for patients with liver failure, we developed a new in vivo model named the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model. Using the GFP/CCl4 model, we found that transplanted Liv8-negative cells efficiently repopulated into cirrhotic liver tissue and differentiated into albumin-producing hepatocytes under persistent liver damage induced by carbon tetrachloride. Moreover, bone marrow cell transplantation into mice with liver cirrhosis improved liver function and liver fibrosis with the strong expression of matrix metalloproteinases (MMPs), especially MMP-9 activity, resulting in an improved survival rate. Results from the GFP/CCl4 model showed that cell therapy using autologous bone marrow cells has the potential to become an effective treatment for patients with liver failure. A summary of findings from the GFP/CCl4 model is described.
引用
收藏
页码:197 / 202
页数:5
相关论文
共 317 条
[1]  
Alison MR(2000)Hepatocytes from non-hepatic adult stem cells Nature (Lond) 406 257-16
[2]  
Poulsom R(2000)Liver from bone marrow in humans Hepatology 32 11-746
[3]  
Jeffery R(2000)Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells N Engl J Med 346 738-1017
[4]  
Dhillon AP(2002)Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract Nat Med 8 1011-163
[5]  
Quaglia A(2002)A new cell therapy using bone marrow cells to repair damaged liver J Gastroenterol 37 162-558
[6]  
Jacob J(2003)An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes J Biochem (Tokyo) 134 551-1426
[7]  
Novelli M(1998)Treatment of the Crigler–Najjar syndrome type I with hepatocyte transplantation N Engl J Med 338 1422-318
[8]  
Prentice G(2002)Hepatocyte transplantation as a treatment for glycogen storage disease type 1a Lancet 359 317-46
[9]  
Williamson J(2003)Autologous bone-marrow stem-cell transplantation for myocardial regeneration Lancet 361 45-374
[10]  
Wright NA(2003)Adult bone marrow is a rich source of human mesenchymal “stem” cells but umbilical cord and mobilized adult blood are not Br J Haematol 121 368-1215