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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

Functional annotation and KEGG molecular pathway analysis.(A) Enriched functional categories in the HC high/HT low group (B) Enriched functional categories in the HC low/HT high group. (C) KEGG pathway heat map of the differentially expressed genes. The HC high/HT low group was linked to MAPK, p53, and Toll-like receptor signaling pathways. The HC low/HT high group was linked to focal adhesion and renal cell carcinoma.
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pone.0135574.g004: Functional annotation and KEGG molecular pathway analysis.(A) Enriched functional categories in the HC high/HT low group (B) Enriched functional categories in the HC low/HT high group. (C) KEGG pathway heat map of the differentially expressed genes. The HC high/HT low group was linked to MAPK, p53, and Toll-like receptor signaling pathways. The HC low/HT high group was linked to focal adhesion and renal cell carcinoma.

Mentions: The HC high/HT low and HC low/HT high groups were analyzed for functional annotation and KEGG molecular pathway enrichment. Gene ontology analysis of the 183 differentially expressed genes in the HC high/HT low group revealed that they were related to developmental processes, immune response and cell death (Fig 4A). KEGG molecular pathways enriched in this group included MAPK, p53, and Toll-like receptor signaling pathways (Fig 4C, Table 1).


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)

Functional annotation and KEGG molecular pathway analysis.(A) Enriched functional categories in the HC high/HT low group (B) Enriched functional categories in the HC low/HT high group. (C) KEGG pathway heat map of the differentially expressed genes. The HC high/HT low group was linked to MAPK, p53, and Toll-like receptor signaling pathways. The HC low/HT high group was linked to focal adhesion and renal cell carcinoma.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135574.g004: Functional annotation and KEGG molecular pathway analysis.(A) Enriched functional categories in the HC high/HT low group (B) Enriched functional categories in the HC low/HT high group. (C) KEGG pathway heat map of the differentially expressed genes. The HC high/HT low group was linked to MAPK, p53, and Toll-like receptor signaling pathways. The HC low/HT high group was linked to focal adhesion and renal cell carcinoma.
Mentions: The HC high/HT low and HC low/HT high groups were analyzed for functional annotation and KEGG molecular pathway enrichment. Gene ontology analysis of the 183 differentially expressed genes in the HC high/HT low group revealed that they were related to developmental processes, immune response and cell death (Fig 4A). KEGG molecular pathways enriched in this group included MAPK, p53, and Toll-like receptor signaling pathways (Fig 4C, Table 1).

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