Bone marrow contributes to renal parenchymal turnover and regeneration

Abstract

In order to establish whether extra-renal cells contribute to the turnover and repair of renal tissues, this study examined kidneys of female mice that had received a male bone marrow transplant and kidney biopsies from male patients who had received kidney transplants from female donors. By using in situ hybridization to detect Y-chromosomes it could be demonstrated that circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells. In the human renal grafts it was confirmed that some of the recipient-derived cells within the kidney exhibited a tubular epithelial phenotype, by combining in situ hybridization with immunostaining for the epithelial markers CAM 5.2 and the lectin Ulex europaeus. Female mouse recipients of male bone marrow grafts showed co-localization of Y-chromosomes and tubular epithelial markers Ricinus communis and Lens culinaris, and a specific cytochrome P450 enzyme (CYP1A2) indicating an appropriate functional capability of clustered newly formed marrow-derived tubular epithelial cells. Y-chromosome-containing cells were observed within glomeruli, with morphology and location appropriate for podocytes. Within the murine kidney, these Y-chromosome-positive cells were negative for the mouse macrophage marker F4/80 antigen and leukocyte common antigen, but were vimentin-positive. The presence of bone marrow-derived cells was noted in both histologically normal mouse kidneys and in human transplanted kidneys suffering damage from a variety of causes. These data indicate that bone marrow cells contribute to both normal turnover of renal epithelia and regeneration after damage, and it is suggested that this could be exploited therapeutically.

Stem cell options for kidney disease

“…It has long been proposed that bone marrow, a known source of stem cells, might be able to contribute to the repair of other organs [17]. Early reports noted the presence of bone marrow-derived cells in the kidney, using sex-mismatching of bone marrow donor and recipient [18]. Additionally, it was noted by Imasawa et al [19] that mice with a spontaneous presentation of IgA nephropathy showed disease amelioration after bone marrow transplantation from an unaffected donor.…”

Hepatic and renal differentiation from blood-borne stem cells

“…23 We have also found occasional male endothelial cells in female kidneys grafted into male recipients, 16 however other groups have reported no evidence of revascularization by the recipient, even in cases where the transplant failed. 24 …”

“…We have used in situ hybridization for the Y chromosome in female mice that have received male whole bone marrow transplants to demonstrate the bone marrow origin of a wide range of kidney cell types, including tubular epithelial cells (Figure 1e), interstitial cells and podocytes. 16 Other groups have found evidence for the mesangial cell differentiation of BMSCs. 17 In our studies, up to 8% of the renal tubular epithelium was found to be of bone marrow origin.…”

Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchymain vivo1

“…One recent study showed that highly purified hematopoietic stem cells even have the potential to differentiate into muscle [19] . Moreover, Poulsom et al [24] found that bone marrow cells could differentiate into both epithelial cells of the renal tubule and podocytes of glomerulus in the adult mouse kidney. Taken together, the pluripotency has been confirmed in most stem cells types.…”