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Open Access Research article

The fate of bone marrow-derived cells carrying a polycystic kidney disease mutation in the genetically normal kidney

Elizabeth Verghese12, Chad Johnson3, John F Bertram4, Sharon D Ricardo2 and James A Deane25*

Author Affiliations

1 Biomedical and Health Sciences, Victoria University, St Albans, Australia

2 Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Australia

3 Monash Micro Imaging, Monash University, Clayton, Australia

4 Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia

5 Current Address: The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Australia

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BMC Nephrology 2012, 13:91  doi:10.1186/1471-2369-13-91

Published: 29 August 2012

Abstract

Background

Polycystic Kidney Disease (PKD) is a genetic condition in which dedifferentiated and highly proliferative epithelial cells form renal cysts and is frequently treated by renal transplantation. Studies have reported that bone marrow-derived cells give rise to renal epithelial cells, particularly following renal injury as often occurs during transplantation. This raises the possibility that bone marrow-derived cells from a PKD-afflicted recipient could populate a transplanted kidney and express a disease phenotype. However, for reasons that are not clear the reoccurrence of PKD has not been reported in a genetically normal renal graft. We used a mouse model to examine whether PKD mutant bone marrow-derived cells are capable of expressing a disease phenotype in the kidney.

Methods

Wild type female mice were transplanted with bone marrow from male mice homozygous for a PKD-causing mutation and subjected to renal injury. Y chromosome positive, bone marrow-derived cells in the kidney were assessed for epithelial markers.

Results

Mutant bone marrow-derived cells were present in the kidney. Some mutant cells were within the bounds of the tubule or duct, but none demonstrated convincing evidence of an epithelial phenotype.

Conclusions

Bone marrow-derived cells appear incapable of giving rise to genuine epithelial cells and this is the most likely reason cysts do not reoccur in kidneys transplanted into PKD patients.

Keywords:
Bone marrow-derived epithelial cells; Cyst; Hematopoietic stem cells; Polycystic kidney disease; Proliferation; Renal injury