Roles of bone marrow cells in glomerular diseases

被引:13
作者
Toshiyuki Imasawa
机构
[1] Fourth Dept. of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kamoda, Kawagoe, Saitama 350-8550
来源
Journal of Clinical and Experimental Nephrology | 2003年 / 7卷 / 3期
关键词
Bone marrow transplantation; Bone marrow-derived mesangial cells; Glomerular homeostasis; Glomerular remodeling; IgA nephropathy; Stem cell disease;
D O I
10.1007/s10157-003-0248-9
中图分类号
学科分类号
摘要
Bone marrow transplantation (BMT) has been used as a tool to investigate various roles of bone marrow cells in glomerular diseases. BMT from IgA nephropathy-prone mice caused glomerular IgA deposition associated with increased circulating macromolecular IgA in normal recipients. Conversely, glomerular mesangial lesions of IgA nephropathy-prone mice were markedly diminished by BMT from normal donors, and the circulating levels of macromolecular IgA were also decreased in the recipients. These data suggest that IgA nephropathy may be a stem-cell disease. BMT clearly decreased the glomerular injuries in glomerular diseases other than murine IgA nephropathy. Theoretically, one mechanism underlying the therapeutic effect of BMT is the replacement of the recipient's destructive immune cells with the donor's bone marrow cells. Interestingly, when BMT was performed by using bone marrow cells of green fluorescent protein (GFP) transgenic mice to investigate the differentiation of bone marrow stem cells in recipients, it was revealed that bone marrow-derived cells differentiated into glomerular cells in mice receiving BMT. This result suggests an alternative mechanism, in that bone marrow cells not only replace harmful immune cells but that they also replenish injured glomerular cells in BMT recipients, which results in the repair of glomerular lesions after BMT. In addition, the glomerular remodeling could participate in maintaining glomerular homeostasis. If the mechanisms of glomerular remodeling are investigated, this could offer a new therapeutic strategy for the repair of glomerular injuries.
引用
收藏
页码:179 / 185
页数:6
相关论文
共 59 条
[21]  
Lai K.N., To W.Y., Li P.K., Leung J.C., Increased binding of polymeric lambda-IgA to cultured human mesangial cells in IgA nephropathy, Kidney Int, 49, pp. 839-845, (1996)
[22]  
Lai K.N., Ho R.T., Lai C.K., Chan C.H., Li P.K., Increase of both circulating Th1 and Th2 T lymphocyte subsets in IgA nephropathy, Clin Exp Immunol, 96, pp. 116-121, (1994)
[23]  
De Caestecker M.P., Bottomley M., Telfer B.A., Hutchinson I.V., Vose B.M., Ballardie F.W., Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy, Kidney Int, 44, pp. 1298-1308, (1993)
[24]  
Rifai A., Schena F.P., Montinaro V., Mele M., D'Addabbo A., Nitti L., Et al., Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy, Lab Invest, 61, pp. 381-388, (1989)
[25]  
Berger J., Recurrence of IgA nephropathy in renal allografts, Am J Kidney Dis, 12, pp. 371-372, (1988)
[26]  
Silva F.G., Chander P., Pirani C.L., Hardy M.A., Disappearance of glomerular mesangial IgA deposits after renal allograft transplantation, Transplantation, 33, pp. 241-246, (1982)
[27]  
Sakai O., IgA nephropathy: Current concepts and future trends, Nephrology, 3, pp. 2-3, (1997)
[28]  
Imasawa T., Utsunomiya Y., Kawamura T., Nagasawa R., Maruyama N., Sakai O., Evidence suggesting the involvement of hematopoietic stem cells in the pathogenesis of IgA nephropathy, Biochem Biophys Res Commun, 249, pp. 605-611, (1998)
[29]  
Imasawa T., Nagasawa R., Utsunomiya Y., Kawamura T., Zhong Y., Makita N., Et al., Bone marrow transplantation attenuates murine IgA nephropathy: Role of a stem cell disorder, Kidney Int, 56, pp. 1809-1817, (1999)
[30]  
Imai H., Nakamoto Y., Asakura K., Miki K., Yasuda T., Miura A.B., Spontaneous glomerular IgA deposition in ddY mice: An animal model of IgA nephritis, Kidney Int, 27, pp. 756-761, (1985)