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Updated: Jul 20, 2026
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors
F Cornacchia1, A Fornoni, A R Plati
1Vascular Biology Institute, University of Miami School of Medicine, Miami, Florida 33136, USA.
Abstract:
We found that ROP Os/+ (Os/+) mice had diffuse glomerulosclerosis and glomerular hypertrophy and that their mesangial cells (the vascular smooth muscle cells of the glomerulus) displayed an apparent sclerosing phenotype. Since mesangial cells are the major source of scar tissue in glomerulosclerosis, we postulated that the sclerosis phenotype was carried by mesangial cell progenitors and that this phenotype could be derived from the bone marrow (BM). Therefore, we transplanted BM from Os/+ mice into congenic ROP +/+ mice (+/+ mice), which have normal glomeruli. We found that glomeruli of +/+ recipients of Os/+ marrow contained the Os/+ genotype, were hypertrophied, and contained increased extracellular matrix. Clones of recipient glomerular mesangial cells with the donor genotype were found in all +/+ recipients that developed mesangial sclerosis and glomerular hypertrophy, whereas +/+ recipients of +/+ BM had normal glomeruli. Thus, the sclerotic (Os/+) or normal (+/+) genotype and phenotype were present in, and transmitted by, BM-derived progenitors. These data show that glomerular mesangial cell progenitors are derived from the BM and can deliver a disease phenotype to normal glomeruli. Glomerular lesions may therefore be perpetuated or aggravated, rather than resolved, by newly arriving progenitor cells exhibiting a disease phenotype.
Insights
Bone marrow progenitor cells can transmit glomerulosclerosis. Transplanting bone marrow from affected mice into healthy mice caused kidney disease, indicating progenitors drive glomerular damage.
Area of Science:
- Nephrology
- Stem Cell Biology
- Genetics
Background:
- Glomerulosclerosis involves scar tissue formation in the kidney's glomeruli.
- Mesangial cells are key contributors to glomerular scarring.
- The origin of mesangial cell progenitors in glomerulosclerosis was unclear.
Purpose of the Study:
- To investigate if bone marrow (BM)-derived progenitors carry and transmit the glomerulosclerosis phenotype.
- To determine the role of BM progenitors in the development of kidney disease.
Main Methods:
- Bone marrow transplantation from Os/+ mice (prone to glomerulosclerosis) into congenic ROP +/+ mice (normal glomeruli).
- Genotyping of recipient glomeruli to identify donor-derived cells.
- Histological analysis of kidney tissues to assess glomerular morphology and extracellular matrix deposition.
Main Results:
- Recipient glomeruli receiving Os/+ BM exhibited the Os/+ genotype, hypertrophy, and increased extracellular matrix.
- Donor-derived mesangial cell clones were identified in glomeruli with sclerosis and hypertrophy.
- +/+ BM recipients maintained normal glomeruli, confirming the disease-associated genotype/phenotype transmission.
Conclusions:
- Glomerular mesangial cell progenitors are derived from the bone marrow.
- These BM-derived progenitors can transmit a disease phenotype, leading to glomerulosclerosis and glomerular hypertrophy in normal kidneys.
- Newly arriving progenitor cells with a disease phenotype may perpetuate or worsen glomerular lesions.
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