Abstract
Recent studies have shown bone marrow (BM) cells to differentiate into a variety of cell types and to thereby participate in the reconstitution of damaged organs. In the present study, we examined the extent to which BM-derived cells are incorporated into glomeruli during recovery from experimentally induced nephritis. To investigate the localization of BM cells in glomeruli, chimeric mice were prepared by transplanting BM cells from green fluorescent protein (GFP) transgenic mice into wild-type mice. Five weeks later, glomerulonephritis was induced by intravenous injection of Habu snake venom. Groups of mice were then killed every few days for 42 d, and harvested kidney samples were subjected to immunohistochemical and immunoelectron microscopic analyses with the aim of detecting the presence of GFP(+) cells within glomeruli. Chimeric animals injected with Habu venom developed proliferative glomerulonephritis within 1–3 d. The lesion gradually subsided and the glomerular structure returned to normal within 42 d. Consistent with the disease course, large numbers of GFP(+) cells were present within glomeruli on d 1–3, but most had disappeared by d 7. Nevertheless, some GFP(+) cells did remain within glomeruli showing mesangial proliferative changes, and were found to express thrombomodulin (TM), a specific endothelial cell marker. These GFP-TM–double-positive cells accounted for a mean of 1.31–2.24% of the total glomerular nuclei from d 7 through d 42, levels that remained stable for at least 12 mo. It thus appears that BM cells can give rise to endothelial cells that participate in the remodeling of glomeruli.
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Abbreviations
- BM:
-
bone marrow
- E-GFP:
-
enhanced green fluorescent protein
- GFP:
-
green fluorescent protein
- HSV:
-
Habu snake venom
- TM:
-
thrombomodulin
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Acknowledgements
The authors thank Dr. David Stern and Dr. Yukio Yuzawa, Columbia University, New York, NY, for providing the anti-TM antibody; Ms. Kyoko Wakamatsu, Mr. Takashi Arai, and Ms. Arimi Ishikawa for expert technical assistance; Dr. Shigeru Sato, Ms. Akiko Adachi, and Mr. Yoshihiro Sasaki for technical support of electron microscopy; and Dr. Akira Shimizu, Dr. Ryuji Ohashi, Dr. Hiroshi Kitamura, Dr. Yukinari Masuda, Dr. Yuichi Sugisaki, Dr. Yu Fukuda, and Dr. Nobuaki Yamanaka for helpful discussions and advices.
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Hayakawa, M., Ishizaki, M., Hayakawa, J. et al. Role of Bone Marrow Cells in the Healing Process of Mouse Experimental Glomerulonephritis. Pediatr Res 58, 323–328 (2005). https://doi.org/10.1203/01.PDR.0000169997.45684.05
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DOI: https://doi.org/10.1203/01.PDR.0000169997.45684.05
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