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Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.

Sung DK, Chang YS, Ahn SY, Sung SI, Yoo HS, Choi SJ, Kim SY, Park WS - PLoS ONE (2015)

Bottom Line: However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration.Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group.These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC) transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t.) versus intravenous (i.v.) MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i.t. (5×10(5)) or i.v. (2×10(6)) route at postnatal day (P) 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV), indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both i.t. and i.v. transplantations. However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group. Although the i.t. group received only one fourth of the number of MSCs that the i.v. group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the i.t. group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group. Thus, local i.t. MSC transplantation was more effective than systemic i.v. MSC administration in protecting against neonatal hyperoxic lung injury.

No MeSH data available.


Related in: MedlinePlus

Histological and morphometric analysis of lung tissue from P14 rats.Hematoxylin and eosin-stained lung sections from representative animals (scale bar = 200 μm, × 100). The NC group shows normal alveolar development. The HC group shows disrupted alveolar development, with larger and simpler alveoli. The HT and HV groups both show attenuated lung morphometric changes upon stem cell transplantation. The degrees of alveolarization, as measured by the mean linear intercept (MLI) and mean alveolar volume (MAV), of P14 rat lungs are shown. MLI and MAV in the HT and HV groups are significantly lower than in the HC group. MAV in the HT group is significantly lower than in the HC and HV group. * P < 0.05 vs. NC; #P < 0.05 vs. HC; $P < 0.05 vs. HV (n = 7 per group).
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pone.0135574.g003: Histological and morphometric analysis of lung tissue from P14 rats.Hematoxylin and eosin-stained lung sections from representative animals (scale bar = 200 μm, × 100). The NC group shows normal alveolar development. The HC group shows disrupted alveolar development, with larger and simpler alveoli. The HT and HV groups both show attenuated lung morphometric changes upon stem cell transplantation. The degrees of alveolarization, as measured by the mean linear intercept (MLI) and mean alveolar volume (MAV), of P14 rat lungs are shown. MLI and MAV in the HT and HV groups are significantly lower than in the HC group. MAV in the HT group is significantly lower than in the HC and HV group. * P < 0.05 vs. NC; #P < 0.05 vs. HC; $P < 0.05 vs. HV (n = 7 per group).

Mentions: Representative light microscope photomicrographs showing the histopathological differences between the experimental groups are shown in Fig 3A. While small and uniform alveoli were observed in the NC group, the alveoli in the HC group were fewer and larger. The HC group also exhibited focal airspace enlargement and heterogeneous alveolar sizes, which are indicative of an impaired alveolarization. These hyperoxia-induced morphological changes and the impaired alveolar growth were attenuated after MSC transplantation, particularly in the HT group compared to the HV group. Morphometric analysis revealed that the MLI and MAV, which represent the mean size and volume of the alveoli respectively, were significantly higher in the HC group than in the NC group (Fig 3B). These hyperoxia-induced morphometric abnormalities were significantly attenuated in the HT and HV groups, with a greater attenuation of the alveolar volume in the HT group than in the HV group.


Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.

Sung DK, Chang YS, Ahn SY, Sung SI, Yoo HS, Choi SJ, Kim SY, Park WS - PLoS ONE (2015)

Histological and morphometric analysis of lung tissue from P14 rats.Hematoxylin and eosin-stained lung sections from representative animals (scale bar = 200 μm, × 100). The NC group shows normal alveolar development. The HC group shows disrupted alveolar development, with larger and simpler alveoli. The HT and HV groups both show attenuated lung morphometric changes upon stem cell transplantation. The degrees of alveolarization, as measured by the mean linear intercept (MLI) and mean alveolar volume (MAV), of P14 rat lungs are shown. MLI and MAV in the HT and HV groups are significantly lower than in the HC group. MAV in the HT group is significantly lower than in the HC and HV group. * P < 0.05 vs. NC; #P < 0.05 vs. HC; $P < 0.05 vs. HV (n = 7 per group).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549285&req=5

pone.0135574.g003: Histological and morphometric analysis of lung tissue from P14 rats.Hematoxylin and eosin-stained lung sections from representative animals (scale bar = 200 μm, × 100). The NC group shows normal alveolar development. The HC group shows disrupted alveolar development, with larger and simpler alveoli. The HT and HV groups both show attenuated lung morphometric changes upon stem cell transplantation. The degrees of alveolarization, as measured by the mean linear intercept (MLI) and mean alveolar volume (MAV), of P14 rat lungs are shown. MLI and MAV in the HT and HV groups are significantly lower than in the HC group. MAV in the HT group is significantly lower than in the HC and HV group. * P < 0.05 vs. NC; #P < 0.05 vs. HC; $P < 0.05 vs. HV (n = 7 per group).
Mentions: Representative light microscope photomicrographs showing the histopathological differences between the experimental groups are shown in Fig 3A. While small and uniform alveoli were observed in the NC group, the alveoli in the HC group were fewer and larger. The HC group also exhibited focal airspace enlargement and heterogeneous alveolar sizes, which are indicative of an impaired alveolarization. These hyperoxia-induced morphological changes and the impaired alveolar growth were attenuated after MSC transplantation, particularly in the HT group compared to the HV group. Morphometric analysis revealed that the MLI and MAV, which represent the mean size and volume of the alveoli respectively, were significantly higher in the HC group than in the NC group (Fig 3B). These hyperoxia-induced morphometric abnormalities were significantly attenuated in the HT and HV groups, with a greater attenuation of the alveolar volume in the HT group than in the HV group.

Bottom Line: However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration.Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group.These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC) transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t.) versus intravenous (i.v.) MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i.t. (5×10(5)) or i.v. (2×10(6)) route at postnatal day (P) 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV), indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both i.t. and i.v. transplantations. However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group. Although the i.t. group received only one fourth of the number of MSCs that the i.v. group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the i.t. group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group. Thus, local i.t. MSC transplantation was more effective than systemic i.v. MSC administration in protecting against neonatal hyperoxic lung injury.

No MeSH data available.


Related in: MedlinePlus