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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

Analysis of ED-1-positive cells and apoptotic cells.(A) Both HC and HV groups exhibited significantly more ED-1-positive cells than the HT group. ED-1 positive cells were labeled with FITC (green), and nuclei were labeled with DAPI (blue) (scale bars: 25 μm, × 400). (B) Apoptotic cells in the lungs of neonatal rats exposed to hyperoxic (90% oxygen) or normoxic conditions were identified by in situ TUNEL. Apoptotic cells were labeled with FITC (green), and nuclei were labeled with PI (red) (scale bars: 25 μm, × 400). The lungs of rat lungs exposed to hyperoxic conditions exhibited increased numbers of apoptotic cells compared to control rats. Less TUNEL-positive cells were detected in the HT group than in the HT and HV groups.* 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.g005: Analysis of ED-1-positive cells and apoptotic cells.(A) Both HC and HV groups exhibited significantly more ED-1-positive cells than the HT group. ED-1 positive cells were labeled with FITC (green), and nuclei were labeled with DAPI (blue) (scale bars: 25 μm, × 400). (B) Apoptotic cells in the lungs of neonatal rats exposed to hyperoxic (90% oxygen) or normoxic conditions were identified by in situ TUNEL. Apoptotic cells were labeled with FITC (green), and nuclei were labeled with PI (red) (scale bars: 25 μm, × 400). The lungs of rat lungs exposed to hyperoxic conditions exhibited increased numbers of apoptotic cells compared to control rats. Less TUNEL-positive cells were detected in the HT group than in the HT and HV groups.* P < 0.05 vs. NC; #P < 0.05 vs. HC; $P < 0.05 vs. HV. (n = 7 per group)

Mentions: The numbers of ED-1-positive and TUNEL-positive cells per high power field were significantly higher in the HC group than in the NC group (Fig 5). This hyperoxia-induced increase in the number of ED-1 positive cells was significantly attenuated in both the HT and HV groups, with more attenuation in the HT group (Fig 5A). Moreover, the increase in the number of TUNEL-positive cells observed in the HC group was significantly attenuated only in the HT group and not in the HV group (Fig 5B).


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)

Analysis of ED-1-positive cells and apoptotic cells.(A) Both HC and HV groups exhibited significantly more ED-1-positive cells than the HT group. ED-1 positive cells were labeled with FITC (green), and nuclei were labeled with DAPI (blue) (scale bars: 25 μm, × 400). (B) Apoptotic cells in the lungs of neonatal rats exposed to hyperoxic (90% oxygen) or normoxic conditions were identified by in situ TUNEL. Apoptotic cells were labeled with FITC (green), and nuclei were labeled with PI (red) (scale bars: 25 μm, × 400). The lungs of rat lungs exposed to hyperoxic conditions exhibited increased numbers of apoptotic cells compared to control rats. Less TUNEL-positive cells were detected in the HT group than in the HT and HV groups.* 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

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getmorefigures.php?uid=PMC4549285&req=5

pone.0135574.g005: Analysis of ED-1-positive cells and apoptotic cells.(A) Both HC and HV groups exhibited significantly more ED-1-positive cells than the HT group. ED-1 positive cells were labeled with FITC (green), and nuclei were labeled with DAPI (blue) (scale bars: 25 μm, × 400). (B) Apoptotic cells in the lungs of neonatal rats exposed to hyperoxic (90% oxygen) or normoxic conditions were identified by in situ TUNEL. Apoptotic cells were labeled with FITC (green), and nuclei were labeled with PI (red) (scale bars: 25 μm, × 400). The lungs of rat lungs exposed to hyperoxic conditions exhibited increased numbers of apoptotic cells compared to control rats. Less TUNEL-positive cells were detected in the HT group than in the HT and HV groups.* P < 0.05 vs. NC; #P < 0.05 vs. HC; $P < 0.05 vs. HV. (n = 7 per group)
Mentions: The numbers of ED-1-positive and TUNEL-positive cells per high power field were significantly higher in the HC group than in the NC group (Fig 5). This hyperoxia-induced increase in the number of ED-1 positive cells was significantly attenuated in both the HT and HV groups, with more attenuation in the HT group (Fig 5A). Moreover, the increase in the number of TUNEL-positive cells observed in the HC group was significantly attenuated only in the HT group and not in the HV group (Fig 5B).

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