***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The aim of the present study was to investigate the effect of bone marrow‑derived mesenchymal stem cells ( BMSCs ) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia ( BPD ) and examine the underlying mechanisms . A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days . BMSCs were isolated , cultured and then labeled with green fluorescent protein . Cells ( 1x106 ) were subsequently injected intravenously 1 h prior to high oxygen treatment . Animals were r and omly divided into three groups ( n=5 in each ) : Control group , BPD model group and BMSC injection group . At two weeks post‑treatment , the expression of transforming growth factor‑β1 ( TGF‑β1 ) , vascular endothelial growth factor ( VEGF ) and von Willebr and factor ( vWF ) was detected using immunohistochemical staining and immunofluorescence . Compared with the BPD model group , the body weight , airway structure and levels of TGF‑β1 and VEGF were significantly improved in the BMSC‑treated group . Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF , which are markers of vascular tissues . The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxia‑induced injury . This provides novel information which may be used to guide further investigation into the use of stem cells in BPD For scientific , ethical and economic reasons , experiments involving animals should be appropriately design ed , correctly analysed and transparently reported . This increases the scientific validity of the results , and maximises the knowledge gained from each experiment . A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be review ed , analysed and repeated . Omitting essential information can raise scientific and ethical concerns . We report the findings of a systematic survey of reporting , experimental design and statistical analysis in published biomedical research using laboratory animals . Medline and EMBASE were search ed for studies reporting research on live rats , mice and non-human primates carried out in UK and US publicly funded research establishments . Detailed information was collected from 271 publications , about the objective or hypothesis of the study , the number , sex , age and /or weight of animals used , and experimental and statistical methods . Only 59 % of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used . Appropriate and efficient experimental design is a critical component of high- quality science . Most of the papers surveyed did not use r and omisation ( 87 % ) or blinding ( 86 % ) , to reduce bias in animal selection and outcome assessment . Only 70 % of the publications that used statistical methods described their methods and presented the results with a measure of error or variability . This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals . Scientific publication is a powerful and important source of information ; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively , accurately and transparently , and peer review ers and journal editors share the responsibility to ensure that published studies fulfil these criteria OBJECTIVE To evaluate whether human mesenchymal stem cells ( hMSCs ) administration alter the clinical course of hyperoxia-induced lung injury . METHODS hMSCs were obtained from bone marrow aspirates from healthy donors after informed consent was signed , hMSCs were separated , cultured , amplified , identified and labeled with BrdU. For BrdU labeling , a sterile stock solution was added to the culture medium 48 h before the end of culture , at a final concentration of 10 micromol/L. Thirty-two 3-day old SD rats from four litters were r and omly divided into four groups , as hyperoxia exposed + hMSC group ( A ) , air-exposed + hMSC group ( B ) , hyperoxia exposed group ( C ) , and air-exposed group ( D ) . The rats from the group A and the group C were placed in a sealed Plexiglas chamber with a minimal in- and outflow , providing six to seven exchanges per hour of the chamber volume and maintaining O2 levels above 95 % , while the rats in the group B and the group D were only exposed to room air . Seven days later , all of them were taken out of the chamber , rats in the group A and B were injected intraperitoneally with hMSCs ( 1 x 10(5 ) in 50 microl of PBS ) immediately , while the rats in the group C and D were only treated with 50 microl of PBS 3 days later . All the animals were sacrificed by an injection of sodium pentobarbital ( 120 mg/kg ) , perfused with cold 0.9 % NaCl , and the left lungs were removed , the upper lobes of which were ground as tissue homogenates and used for ELISA , while the inferior lobes were stored at -70 degrees C until use for RT-PCR . The right lungs were fixed in situ for 2 h by the intratracheal instillation with 10 % neutral formalin and then postfixed for 24 h. Sagittal sections ( 4-microm ) of paraffin-embedded middle lobe and upper lobe of the right lung were used for immunohistochemistry and histology , respectively . RESULTS ( 1 ) There was a significant difference in the value of RAC ( raditive alveoli coant ) among the 4 groups ( 11.145 + /- 1.331 , 13.941 + /- 0.985 , 9.595 + /- 0.672 , 14.819 + /- 1.080 , F = 43.234 , P = 0.000 ) . RAC in group A and C were significantly reduced compared with subjects in group D ( P < 0.05 , P < 0.05 ) ; and there was also a significant difference between group A and group C ( P < 0.05 ) , but not between group B and D subjects ( P > 0.05 ) . ( 2 ) There were significant differences in the levels of both TNFalpha and TGFbeta(1 ) in the homogenate of lungs among the 4 groups ( 142.933 + /- 24.017 , 79.033 + /- 11.573 , 224.088 + /- 41.915 , 76.500 + /- 10.373 , F = 59.970 , P = 0.000 ; 1726.484 + /- 91.086 , 1530.359 + /- 173.441 , 2047.717 + /- 152.057 , 1515.777 + /- 131.049 , F = 24.977 , P = 0.000 ) . The levels of TNFalpha and TGFbeta1 were significantly elevated in both group A and group C when compared with subjects in group D ( P < 0.05 for both ) . Concentrations of TNFalpha and TGFbeta1 were both significantly decreased in group A versus group C ( P < 0.05 for both ) . There was no significant difference between group B and D subjects in the fields of TNFalpha and TGFbeta(1 ) ( P > 0.05 for both ) . ( 3 ) BrdU-labelled cells were observed at alveolar wall and bronchioles in both group A and group B , and there was a significant difference in BrdU-labeled cells between two groups ( 0.230 + /- 0.026 , 0.190 + /- 0.015 ; t = 3.769 , P = 0.002 ) , but none was found in group C and group D. Electrophoresis of the PCR products showed a 224 bp b and , specific for Alu mRNA , in 7 of 8 rats of group A and 5 of 8 rats of group B , respectively , but no such b and was found in group C and group D. CONCLUSION hMSCs administered by intraperitoneal injection could be implanted in the lungs of newborn rats , and they could effectively protect the rats against damage to the lungs caused by hyperoxia OBJECTIVE To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell ( MSC ) transplantation in preterm infants . STUDY DESIGN In a phase I dose-escalation trial , we assessed the safety and feasibility of a single , intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia ( BPD ) . The first 3 patients were given a low dose ( 1 × 10(7 ) cells/kg ) of cells , and the next 6 patients were given a high dose ( 2 × 10(7 ) cells/kg ) . We compared their adverse outcomes , including BPD severity , with those of historical case-matched comparison group . RESULTS Intratracheal MSC transplantation was performed in 9 preterm infants , with a mean gestational age of 25.3 ± 0.9 weeks and a mean birth weight of 793 ± 127 g , at a mean of 10.4 ± 2.6 days after birth . The treatments were well tolerated , without serious adverse effects or dose-limiting toxicity attributable to the transplantation . Levels of interleukin-6 , interleukin-8 , matrix metalloproteinase-9 , tumor necrosis factor α , and transforming growth factor β1 in tracheal aspirates at day 7 were significantly reduced compared with those at baseline or at day 3 posttransplantation . BPD severity was lower in the transplant recipients , and rates of other adverse outcomes did not differ between the comparison group and transplant recipients . CONCLUSION Intratracheal transplantation of allogeneic hUCB-derived MSCs in preterm infants is safe and feasible , and warrants a larger and controlled phase II study Background : Mesenchymal stem cell ( MSC ) therapy may prevent neonatal hyperoxia-induced lung injury ( HILI ) . There are , however , no clear data on the therapeutic efficacy of MSC therapy in established HILI , the duration of the reparative effects , and the exact mechanisms of repair . The main objective of this study was to evaluate whether the long-term reparative effects of a single intratracheal ( IT ) dose of MSCs or MSC-conditioned medium ( CM ) are comparable in established HILI . Methods : Newborn rats exposed to normoxia or hyperoxia from postnatal day (P)2)–P16 were r and omized to receive IT MSCs , IT CM , or IT placebo ( PL ) on P9 . Alveolarization and angiogenesis were evaluated at P16 , P30 , and P100 . Results : At all time periods , there were marked improvements in alveolar and vascular development in hyperoxic pups treated with MSCs or CM as compared with PL . This was associated with decreased expression of inflammatory mediators and an upregulation of angiogenic factors . Of note , at P100 , the improvements were more substantial with MSCs as compared with CM . Conclusion : These data suggest that acute effects of MSC therapy in HILI are mainly paracrine mediated ; however , optimum long-term improvement following HILI requires treatment with the MSCs themselves or potentially repetitive administration of CM Recent evidence suggests mesenchymal stem cells ( MSCs ) can downmodulate bleomycin-induced lung injury , and umbilical cord blood ( UCB ) is a promising source for human MSCs . This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate  hyperoxia-induced lung injury in immunocompetent newborn rats . Wild-type Sprague-Dawley rats were r and omly exposed to 95 % oxygen or air from birth . In the transplantation groups , a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally ( 2 × 106 cells ) or intraperitoneally ( 5 × 105 cells ) at postnatal day ( P ) 5 . At P14 , the harvested lungs were examined for morphometric analyses of alveolarization and TUNEL staining , as well as the myeoloperoxidase activity , the level of tumor necrosis factor (TNF)-α , interleukin (IL)-6 , and transforming growth factor (TGF)-β mRNA , α-smooth muscle actin ( SMA ) protein , and collagen levels . Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation . Despite one fourth dosage of MSCs , significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia . The hyperoxia-induced increase in the number of TUNEL-positive cells , myeloperoixdase activity , and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation . However , the hyperoxia-induced impaired alveolarization and increased the level of TNF-α and TGF-β mRNA , α-SMA protein , and collagen were significantly attenuated only with intratracheal MSCs transplantation . MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged lungs 
    Output:
    
MSCs also significantly ameliorated pulmonary hypertension , lung inflammation , fibrosis , angiogenesis , and apoptosis .
Similarly , MSC-CM significantly improved alveolarization , angiogenesis , and pulmonary artery remodeling .
MSCs , tested exclusively in hyperoxic rodent models of BPD , show significant therapeutic benefit .