This study tests the hypothesis that bone marrow-derived mononuclear cell (BMDMC) therapy may reduce lung inflammation and fibrosis leading to an improvement in respiratory mechanics in a murine model of silicosis.52 female C57BL/6 mice were randomly assigned into four groups. In the silica group (SIL), silica suspension (20 mg/50 mL in saline) was intratracheally instilled. In the control animals, 50 mL saline was administered intratracheally. At 1 h, the control and SIL groups were further randomised, receiving BMDMC (2610 6 In the SIL-cell group, the fraction area of granuloma, the number of macrophages and the collagen fibre content were reduced, yielding improved lung mechanics. The presence of male donor cells in lung tissue was not confirmed using detection of Y chromosome DNA. Nevertheless, caspase-3, IL-1b, IL-1a, IL-1RN and TGF-b mRNA expression diminished after cell therapy.In conclusion, BMDMC acted on inflammatory and fibrogenic processes improving lung function through paracrine effects.

Background/Aims: We investigated the regenerative capacity of intravenous administration of bone marrow–derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by ^99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups (n = 6 each). In the acute lung injury (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 μg, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 × 10(7) cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance (E(st)), resistive (ΔP(1)), and viscoelastic (ΔP(2)) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelial and endothelial repair with multinucleated type II pneumocytes. These histological changes yielded a reduction in lung E(st), ΔP(1), and ΔP(2) compared to ALI. In the present experimental ALI model, the administration of BMDMC yielded a reduction in the inflammatory process and a repair of epithelium and endothelium, reducing the amount of alveolar collapse, thus leading to an improvement in lung mechanics.

The time course of lung mechanics, histology, and inflammatory and fibrogenic mediators are analysed after intratracheal instillation (IT) of bone marrow-derived cells (BMDC) in a model of silicosis. C57BL/6 mice were randomly divided into SIL (silica, 20mg IT) and control (CTRL) groups (saline IT). At day 15, mice received saline or BMDC (2 x 10(6)cells) IT. The biodistribution of technetium-99m BMDC was higher in lungs compared with other organs. At days 30 and 60, lung mechanics, the area of granulomatous nodules, and mRNA expression of IL-1beta and TGF-beta were higher in SIL than CTRL animals. BMDC minimized changes in lung mechanics, the area of granulomatous nodules, and total cell infiltration at day 30, but these effects were no longer observed at day 60. Conversely, BMDC avoided the expression of IL-1beta at days 30 and 60 and TGF-beta only at day 30. In conclusion, BMDC therapy improved lung mechanics and histology, but this beneficial effect was not maintained in the course of injury.

The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic lesions. We present evidence for the improvement of renal morphology in a model of tubulointerstitial fibrosis. Wistar rats were submitted to unilateral ureteral obstruction (UUO), treated with bone-marrow mononuclear cells (UUO+BMMC) infused via the cava vein, and killed on day 14. Labeled BMMC were seen in renal tissue after 7 days in the group UUO+BMMC. UUO+BMMC also showed a reduction in ED1⁺ cells and tubular apoptotic cells together with enhanced tubular proliferation. Myofibroblasts were also reduced after BMMC which is consistent with a decrease in collagen deposition (picro Sirius staining) and RT-PCR data showing lower levels of procollagen-I mRNA. Simultaneously, nestin+ cells increased in the interstitium and decreased in the tubules. Double stained nestin⁺/α-SMA⁺ cells were present only in the interstitium, and their levels did not change after BMMC infusion. These data indicate a renoprotective effect of BMMC through increased tubular cell regeneration, inhibition of tubular cell apoptosis and partially blocking of the inflammatory and fibrotic events that occur after unilateral ureteral obstruction.