Mesenchymal stromal cell turnover in the normal adult lung revisited.

We have employed a simple and robust noninvasive method of continuous in vivo long-term bromodeoxyuridine (BrdU) labeling to analyze lung mesenchymal stromal cell turnover in adult mice in the steady state. Mathematical modeling of BrdU uptake in flow cytometrically sorted CD45(neg)CD31(neg)Sca-1(pos) lung cells following long-term feeding of BrdU to mice in their drinking water reveals that lung mesenchymal stromal cells cycle continuously throughout life. Analysis of BrdU incorporation during long-term feeding and during chasing (delabeling) following replacement of BrdU-water with normal water shows that the CD45(neg)CD31(neg)Sca-1(pos) lung mesenchymal stromal cell compartment turns over at a rate of ∼2.26% per day with a time to half-cycled of 44 days, an estimated cell proliferation rate of 0.004/day, and a cell death rate of 0.018/day.