Renal and bone marrow cells fuse after renal ischemic injury

After acute kidney injury, bone marrow cells contribute to renal repair by converting into renal cells, but the mechanism of this conversion is not well understood. To determine whether cell fusion between bone marrow cells and injured renal cells plays a role, we subjected female mice expressing Cre recombinase in tubular epithelial cells to unilateral renal ischemia-reperfusion injury, and subsequently transplanted male bone marrow cells containing a loxP-flanked reporter gene. After 28 days, cell fusion was detected by polysomy for the sex chromosomes and Cre-mediated activation of the reporter gene. After injury, 1.8% of tubular cells were bone marrow-derived, but Cre/loxP recombination demonstrated a frequency of fusion between tubular epithelial and bone marrow cells of only 0.066% (approximately 7 per 10,000 tubular cells). The second strategy, chromosome fluorescence in situ hybridization (FISH), detected cell fusion in 3.8% of bone marrow-derived tubular epithelial cells. No cell fusion was observed in nonischemic kidneys, suggesting that injury was required for cell fusion. This finding was substantiated in co-culture experiments, because cell fusion was only observed between bone marrow cells and renal tubular cells when the latter were depleted of ATP. In conclusion, bone marrow cells can fuse with renal epithelial cells after ischemic injury, but the low frequency of fusion does not account for the majority of the observed conversion of bone marrow cells into kidney cells.