Bone marrow cells contribute to tubular epithelium regeneration following acute kidney injury induced by mercuric chloride.

Acute tubular necrosis (ATN) caused by renal ischaemia, renal hypo-perfusion, or nephrotoxic substances is the most common form of acute kidney injury (AKI). There are a few treatment options for this life-threatening disease and the mortality rate exceeds 50 per cent. In critical cases of AKI the only option is renal transplantation. In the present study we evaluated whether bone marrow cells (BMCs) are involved in regeneration of kidney tubules following acute tubular necrosis in the mouse. Six to eight week old C57BL6/J and congenic enhanced green fluorescence protein (eGFP) mice were used. The relative contributions of eGFP-expressing BMCs were compared in two different approaches to kidney regeneration in the mercuric chloride (HgCl 2 )-induced mouse model of AKI: induced engraftment and forced engraftment. In vitro differentiation of lineage-depleted (Lin - ) BMCs into renal epithelial cells was also studied. In the forced engraftment approach, BMCs were found to play a role in the regeneration of tubules of renal cortex and outer medulla regions. About 70 per cent of donor-derived cells expressed megalin. In vitro culture revealed that Lin - BMCs differentiated into megalin, E-cadherin and cytokeratin-19 (CK-19) expressing renal epithelial cells. The present results demonstrate that Lin - BMCs may contribute in the regeneration of renal tubular epithelium of HgCl 2 -induced AKI. This study may also suggest a potential role of BMCs in treating AKI.