The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells.
Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not been known to differentiate into glomerular cells. To investigate whether such differentiation is possible, a search was made for donor glomerular cells in lethally irradiated C57BL/6j (B6) mice given transplants of BMC from syngeneic mice transgenic for green fluorescence protein (GFP) ([GFP-->B6] mice). After the recipients of donor BMC manifested GFP-positive cells in their glomeruli, the numbers of such cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after bone marrow transplantation. Immunohistochemical analyses revealed that most GFP-positive cells in the glomeruli were neither macrophages nor T cells. With the use of a laser-scanning confocal microscope, GFP-positive cells were observed within the mesangium of [GFP-->B6] mice. Furthermore, indirect immunofluorescence assays demonstrated that desmin-positive cells in the glomeruli of these chimeric mice were also positive for GFP. Among glomerular cells isolated from [GFP-->B6] mice 24 wk after bone marrow transplantation and then cultured, the majority of cells (approximately 84%) stained for desmin and approximately 60% of the desmin-positive cells expressed GFP. In addition, these GFP-positive cells in the cultures contracted in response to angiotensin II stimulation. These results suggest that bone marrow-derived cells may have the potential to differentiate into glomerular mesangial cells.
Imasawa
Toshiyuki
T
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.|Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan.|Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Utsunomiya
Yasunori
Y
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Kawamura
Tetsuya
T
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Zhong
Y U
YU
Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan.
Nagasawa
Ryuji
R
Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan.|Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Okabe
Masaru
M
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Maruyama
Naoki
N
Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Hosoya
Tatsuo
T
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Ohno
Tsuneya
T
Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D013997:Time Factors; D014019:Tissue Donors
D003893:Desmin; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D000804:Angiotensin II; D049452:Green Fluorescent Proteins