title: Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.
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.
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Dong Kyung
authors: DK
authors: Sung
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Yun Sil
authors: YS
authors: Chang
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: So Yoon
authors: SY
authors: Ahn
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Se In
authors: SI
authors: Sung
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Hye Soo
authors: HS
authors: Yoo
authors: Biomedical Research Institute, MEDIPOST Co., Ltd., Seoul, Korea.
authors: Soo Jin
authors: SJ
authors: Choi
authors: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Soo Yoon
authors: SY
authors: Kim
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Won Soon
authors: WS
authors: Park
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018496:Hyperoxia / Q000235:genetics; D020287:In Situ Nick-End Labeling; D018836:Inflammation Mediators / Q000378:metabolism; D055370:Lung Injury / Q000235:genetics* / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D009930:Organic Chemicals / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D016019:Survival Analysis; D014019:Tissue Donors; D015854:Up-Regulation / Q000235:genetics; D015430:Weight Gain
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009930:Organic Chemicals; C070080:PKH 26; D020011:Protective Agents; D012333:RNA, Messenger