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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

Survival rate and weight growth.(A) Kaplan-Meier survival curve and (B) body weights at postnatal day (P) 14. Normoxia control (NC), hyperoxia control (HC), hyperoxia-exposed rats with intratracheal transplantation of MSCs (HT) and hyperoxia-exposed rats with intravenous transplantation of MSCs (HV) groups, respectively.* P < 0.05 vs. NC; #P < 0.05 vs. HC (n = 18 per group).
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pone.0135574.g001: Survival rate and weight growth.(A) Kaplan-Meier survival curve and (B) body weights at postnatal day (P) 14. Normoxia control (NC), hyperoxia control (HC), hyperoxia-exposed rats with intratracheal transplantation of MSCs (HT) and hyperoxia-exposed rats with intravenous transplantation of MSCs (HV) groups, respectively.* P < 0.05 vs. NC; #P < 0.05 vs. HC (n = 18 per group).

Mentions: Exposure to oxygen (HC group) significantly reduced the survival rate (P < 0.05 vs. NC) by the end of experiment (P14), compared to the 100% survival rate of the NC group. On the contrary, the survival rates of the HT and HV groups were not different when compared to the NC group. There was no difference in the survival rate between the HT and HV groups (Fig 1A).The decrease in body weight gain observed in the HC group was significantly improved in the HT group (P < 0.05 vs. HC), but not in the HV group (Fig 1B).


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)

Survival rate and weight growth.(A) Kaplan-Meier survival curve and (B) body weights at postnatal day (P) 14. Normoxia control (NC), hyperoxia control (HC), hyperoxia-exposed rats with intratracheal transplantation of MSCs (HT) and hyperoxia-exposed rats with intravenous transplantation of MSCs (HV) groups, respectively.* P < 0.05 vs. NC; #P < 0.05 vs. HC (n = 18 per group).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135574.g001: Survival rate and weight growth.(A) Kaplan-Meier survival curve and (B) body weights at postnatal day (P) 14. Normoxia control (NC), hyperoxia control (HC), hyperoxia-exposed rats with intratracheal transplantation of MSCs (HT) and hyperoxia-exposed rats with intravenous transplantation of MSCs (HV) groups, respectively.* P < 0.05 vs. NC; #P < 0.05 vs. HC (n = 18 per group).
Mentions: Exposure to oxygen (HC group) significantly reduced the survival rate (P < 0.05 vs. NC) by the end of experiment (P14), compared to the 100% survival rate of the NC group. On the contrary, the survival rates of the HT and HV groups were not different when compared to the NC group. There was no difference in the survival rate between the HT and HV groups (Fig 1A).The decrease in body weight gain observed in the HC group was significantly improved in the HT group (P < 0.05 vs. HC), but not in the HV group (Fig 1B).

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