title: Cell type-dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury.
abstract: OBJECTIVE
  The aim of this study was to determine the optimal cell type for transplantation to protect against neonatal hyperoxic lung injury. To this end, the in vitro and in vivo therapeutic efficacies and paracrine potencies of human umbilical cord blood-derived mesenchymal stromal cells (HUMs), human adipose tissue-derived mesenchymal stromal cells (HAMs) and human umbilical cord blood mononuclear cells (HMNs) were compared.
  
  
  METHODS
  Hyperoxic injury was induced in vitro in A549 cells by challenge with H2O2. Alternatively, hyperoxic injury was induced in newborn Sprague-Dawley rats in vivo by exposure to hyperoxia (90% oxygen) for 14 days. HUMs, HAMs or HMNs (5 × 10(5) cells) were given intratracheally at postnatal day 5.
  
  
  RESULTS
  Hyperoxia-induced increases in in vitro cell death and in vivo impaired alveolarization were significantly attenuated in both the HUM and HAM groups but not in the HMN group. Hyperoxia impaired angiogenesis, increased the cell death and pulmonary macrophages and elevated inflammatory cytokine levels. These effects were significantly decreased in the HUM group but not in the HAM or HMN groups. The levels of human vascular endothelial growth factor and hepatocyte growth factor produced by donor cells were highest in HUM group, followed by HAM group and then HMN group.
  
  
  CONCLUSIONS
  HUMs exhibited the best therapeutic efficacy and paracrine potency than HAMs or HMNs in protecting against neonatal hyperoxic lung injury. These cell type-dependent variations in therapeutic efficacy might be associated or mediated with the paracrine potency of the transplanted donor cells.
authors: Department of Pediatrics, 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; Samsung Biomedical Research Institute, 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.
authors: Dong Kyung
authors: DK
authors: Sung
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Hye Soo
authors: HS
authors: Yoo
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Se In
authors: SI
authors: Sung
authors: Biomedical Research Institute, MEDIPOST Co., Ltd., Seoul, Korea.
authors: Soo Jin
authors: SJ
authors: Choi
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: wonspark@skku.edu.
authors: Won Soon
authors: WS
authors: Park
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D001997:Bronchopulmonary Dysplasia / Q000628:therapy; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018496:Hyperoxia / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation*; D055370:Lung Injury / Q000473:pathology / Q000628:therapy*; D016676:Macrophages, Alveolar / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; C066855:HGF protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D006861:Hydrogen Peroxide; D010100:Oxygen
keywords: bronchopulmonary dysplasia; cell transplantation; hepatocyte growth factor; vascular endothelial growth factor