Effects of bone-marrow derived mononuclear cells from silicotic and healthy donors in experimental silicosis

Background: Silicosis is a chronic lung disease and with no effective therapy. Aim: To investigate the effects of bone-marrow mononuclear cells (BMMCs) obtained from healthy and silicotic donors on lung morpho-function in experimental silicosis. Methods: C57BL/6 mice were randomly divided in control (C) and silicosis (SIL) groups, intratracheally instilled with saline (50mL) or silica (20mg/50mL), respectively, and then treated intravenously with saline (Sal) or BMMCs (2x10 6 ) from healthy (ht) and silicotic (sc) mice. Results: SIL-Sal group showed higher lung static elastance (Est) (48.7±1.1cmH 2 O.ml -1 ), resistive (DP1) (1.4±0.1cmH 2 O) and viscoelastic (DP2) (1.2±0.1cmH 2 O) pressures than C group (33.7±1.4cmH 2 O.ml -1 ; 0.8±0.1cmH 2 O; 0.8±0.1cmH 2 O, respectively). Est, DP1, and DP2 were lower in SIL-BMMCs-ht (40.2±0.5cmH 2 O.ml -1 ; 1.1±0.1cmH 2 O; 0.8±0.1cmH 2 O) and SIL-BMMCs-sc (41.8±0.9 cmH 2 O.ml -1 ; 1.2±0.1cmH 2 O; 1.0±0.1cmH 2 O) than SIL-Sal group. The degree of apoptosis was higher in SIL-Sal (8.4±1.1%) than SIL-BMMCs-ht (2.5±0.4%) and SIL-BMMCs-sc (3.0±0.2%). SIL-Sal group presented a higher number of mononuclear (MN) and polymorphonuclear (PMN) cells in septae (42.6±1.0%, 8.2±0.7%) and nodules (38.8±0.5%; 11.3±0.7%) than SIL-BMMCs-ht (MN:38.3±1.3% and 36.3±0.8%, PMN: 5.1±0.8%, 7.2±0.9%, respectively) and SIL-BMMCs-sc (MN: 35.3±0.6% and 34.2±0.8%, PMN: 5.8±1.0% and 6.8±0.8%, respectively). SIL-Sal group showed higher fraction area of nodules (58.8±4.3%) than SIL-BMMCs-ht (32.8±2.7%) and SIL-BMMCs-sc (29.0±3.7%). Conclusion: Therapy with BMMCs-sc and BMMCs-ht led to similar improvement in lung mechanics and histology in the current experimental silicosis. Fundings: FAPERJ, CNPq, MS-DECIT.