Bone marrow contributes to renal parenchymal turnover and regeneration

TLDR

The study aimed to determine whether bone marrow–derived cells contribute to renal tissue turnover and repair by analyzing kidneys of mice that received male bone marrow transplants and human kidney grafts from opposite‑sex donors. They used Y‑chromosome in situ hybridization combined with immunostaining for epithelial markers (CAM 5.2, Ulex europaeus, Ricinus communis, Lens culinaris) and functional enzyme CYP1A2 to identify bone marrow–derived cells in mouse and human kidneys. Y‑chromosome–positive bone marrow cells were found in both mouse and human kidneys, differentiating into tubular epithelial cells and podocytes, expressing functional markers such as CYP1A2, and were present in normal and damaged tissues, demonstrating that bone marrow contributes to renal epithelial 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.