Prevention of mesangial sclerosis by bone marrow transplantation.

Abstract

Previously we have shown that bone marrow (BM) transplantation (BMT) can attenuate progression of and even ameliorate mesangial sclerosis (MS) in Wt1-heterozygous mice. However, it is unclear whether BMT performed before the onset of disease will prevent the development of MS. To investigate whether intravenous (i.v.) or intrarenal (i.r.) administration of BM have equal effects on the progression of MS in Wt1-heterozygous mice, young Wt1-heterozygous mice that had not yet developed renal disease were used as recipients for BMT. After preconditioning with 750 cGy radiation, mice were transplanted with one million wild-type BM via i.v. or i.r. administration. All recipients and untreated controls were assessed for urinary albumin loss, renal pathology, and BM donor-derived renal cells over time. Representative kidney samples were subjected to transmission electron microscopy (TEM) analysis. Interestingly, i.r. and i.v. administration of BM cells gave comparable hematopoietic engraftment levels, and both were able to prevent the onset of MS as assessed by improved lifespan, renal function, renal histology, and TEM analysis. Taken together, we show for the first time that MS can be prevented if BMT is performed before disease onset. Similar therapeutic effects were obtained whether the BM was administered i.v. or i.r.

• Authors: J-K Guo, T A Ardito, M Kashgarian, D S Krause
• Journal: Kidney international (Kidney Int) Vol. 70 Issue 5 Pg. 910-3 (Sep 2006) ISSN: 0085-2538 [Print] United States
• PMID: 16850025 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• WT1 Proteins

Topics

• Animals
• Bone Marrow Cells (metabolism, pathology)
• Bone Marrow Transplantation (methods)
• Disease Models, Animal
• Disease Progression
• Gene Expression Regulation
• Hematopoiesis
• Mesangial Cells (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Models, Genetic
• Nephrosclerosis (genetics, pathology, prevention & control)
• Time Factors
• Transplantation Conditioning (methods)
• WT1 Proteins (genetics, metabolism)