Bone marrow cells contribute to regeneration of damaged glomerular endothelial cells

doi:doi:10.1111/j.1523-1755.2005.00291.x

Abstract

Bone marrow cells contribute to regeneration of damaged glomerular endothelial cells.

Background

There is accumulating evidence that adult bone marrow (BM) cells show unexpected plasticity, and can differentiate into a wide range of specialized cells. In the case of intrinsic renal glomerular cells, BM-derived cells have been reported to differentiate into both mesangial cells and podocytes. However, there is controversy on recruitment of glomerular endothelial cells, although endothelial cells in other tissues are known to be recruited from the BM.

Methods

Sprague-Dawley (SD) rats and SD rats made chimeric by transplantation of bone marrow cells from enhanced green fluorescent protein (EGFP) transgenic littermate rats, were injected with anti-Thy-1.1 antibody, followed by unilateral nephrectomy (1-kidney model). Chimeric rats used in 1-kidney model were sacrificed for histologic examination at weeks 2, 4, 8, and 11. We examined isolated glomeruli and frozen sections of kidneys from rats of each group at weeks 2 and 11 by confocal laser scan microsopy (CLSM), both immunohistologically and three dimensionally.

Results

In the 1-kidney group, using chimeric rats transplanted with EGFP(+) bone marrow cells, most rats died, presumably of uremia, after 8 to 11 weeks. A CLSM study using isolated glomeruli and frozen sections of kidneys revealed that bone marrow-derived PECAM-1(+), RECA-1(+) cells, and OX-7(+) cells contributed to the structural support for the glomerular capillaries during the chronic course. Global glomerular sclerotic lesions and diffuse tubular atrophic changes, with interstitial cell infiltration, were remarkable at weeks 8 and 11.

Conclusion

Bone marrow–derived endothelial progenitor cells participated in glomerular endothelial cell turnover after severe damage. Treatment that could target bone marrow–derived endothelial progenitor cells and promote angiogenesis in regions of progressive glomerular lesions may be a promising therapeutic approach for preventing end-stage renal disease.

Keywords:

bone marrow–derived endothelial progenitor cells, reconstitution of glomerular endothelial cells, EGFP-transgenic rats, progressive glomerulosclerosis

Vascular Biology – Hemodynamics – Hypertension