Experimental model Therapeutic cell or product Outcomes Suggested mechanism References Bone marrow-derived MSCs (i.t.) Improved survival Improved alveolar structure/prevented alveolar arrest Prevented vascular growth arrest Improved exercise capacity Reduced pulmonary hypertension Engraftment as AT2 Paracrine mechanisms [48 ] Bone marrow-derived MSCs or CdM (i.v.) Improved alveolar structure/prevented alveolar arrest Attenuated inflammation Prevented vascular growth arrest Prevented pulmonary hypertension Paracrine mechanisms Immunomodulatory effects [54 ] Bone marrow-derived MSCs or CdM (i.v.) Increased number of BASCs Improved alveolar structure/prevented alveolar arrest Stimulation of BASCs Paracrine mechanisms [55 ] Hyperoxia-induced neonatal lung injury Bone marrow-derived MSCs (i.p.) Improved survival Improved alveolar structure/prevented alveolar arrest Attenuated inflammation Inhibited lung fibrosis Engraftment as AT2 Reduction in ECM remodeling and fibrosis gene expression (TGF-
1, collagen 1
, TIMP-1) Anti-inflammatory effects [56 ] Bone marrow-derived MSC-CdM (i.v.) Improved alveolar structure Attenuated myofibroblast infiltration Improved lung function Reversed pulmonary hypertention and RV hypertrophy Attenuated pulmonary arterial remodeling Rescued loss of pulmonary blood vessels Paracrine mechanisms Cytoprotective effects Activation of BASCs [57 ] hUCB-derived MSCs (i.t.) Improved survival and growth restriction Improved alveolar structure Attenuated lung fibrosis, inflammation, and ROS activity Paracrine anti-inflammatory, antifibrotic and antioxidative effects [59 , 60 ] hUCB-derived MSCs and MSC-CdM (i.t.) Umbilical cord-derived PCs and PC-CdM (i.t.) Prevented and restored impaired alveolar growth Improved lung function and exercise capacity Prevented impaired lung angiogenesis Prevented pulmonary arterial wall remodeling and RV hypertrophy Persistent benefit on lung architecture and exercise capacity at 6 months No adverse effects on lung structure in treated control animals at 6 months Paracrine mechanisms [58 ] BMDACs (i.v.) Improved alveolar structure Improved vascular growth Paracrine mechanisms [72 ] LPS-induced (i.a.) neonatal lung injury hAECs (i.t.; i.v.) Improved alveolar structure Increased surfactant protein expression Attenuated inflammation Immunomodulatory effects [73 ]