AEC-II-iPL cells are able to engraft and differentiate to mature AEC-II and AEC-I cells in severely fibrotic lungs. a Experimental schema depicting the in vivo study using male recipients. Lung mechanical function measured by FlexiVent showing PV curves of all the experimental groups, b BLM cell-treated male recipient lungs 2 weeks after receiving either AEC-II-iPL or MSC cells at day 7 of BLM treatment (BLM day7 + iPL+2W, BLM day7 + MSC+2W), and c BLM cell-treated male recipient lungs 1 week after receiving AEC-II-iPL cells or MSC at day 14 of BLM treatment (BLM day14 + iPL+1W, BLM day14 + MSC+1W). d Representative images of whole lungs from all the experimental groups at day 21 of bleomycin (BLM) treatment. e The cell retention rate of engrafted GFP cells in recipient lungs (percentage of day 0 injected cells) was calculated using genomic GFP at day 21 of BLM treatment (relative to β-actin GFP lungs) measured by PCR. f Confocal microscopic images of alveolar epithelium of the saline control, BLM untreated (BLM day21), and BLM cell-treated at day 7 (BLM day7 + iPL+2W, BLM day7 + MSC+2W) or at day 14 (BLM day14 + iPL+1W, BLM day14 + MSC+1W) animals showing nuclear stain DAPI (blue) and LAMP3 (red) and GFP (green) expression. g Expression levels of SPC in recipient lungs, as measured by qRT-PCR, comparing fold differences in the expression to control lungs. h Confocal microscopic images of alveolar epithelium of the saline control, BLM untreated (BLM day21), and BLM cell-treated at day 7 (BLM day7 + iPL+2W, BLM day7 + MSC+2W) and at day 14 (BLM day14 + iPL+1W, BLM day14 + MSC+1W) showing nuclear stain DAPI (blue) and AQP5 (red) and GFP (green). i Expression levels of AQP5 in the recipient lungs, as measured by qRT-PCR, comparing fold differences in the expression to control lungs. For b, c, e, g, i, values are mean ± S.D. of three independent biological replicates *p < 0.05; **p < 0.001; ***p < 0.0001. Scale bar, 100 µm (f); 10 µm (f—zoom and h)