title: Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial.
abstract: OBJECTIVE
  To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell (MSC) transplantation in preterm infants.
  
  
  METHODS
  In a phase I dose-escalation trial, we assessed the safety and feasibility of a single, intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia (BPD). The first 3 patients were given a low dose (1 × 10(7) cells/kg) of cells, and the next 6 patients were given a high dose (2 × 10(7) cells/kg). We compared their adverse outcomes, including BPD severity, with those of historical case-matched comparison group.
  
  
  RESULTS
  Intratracheal MSC transplantation was performed in 9 preterm infants, with a mean gestational age of 25.3 ± 0.9 weeks and a mean birth weight of 793 ± 127 g, at a mean of 10.4 ± 2.6 days after birth. The treatments were well tolerated, without serious adverse effects or dose-limiting toxicity attributable to the transplantation. Levels of interleukin-6, interleukin-8, matrix metalloproteinase-9, tumor necrosis factor α, and transforming growth factor β1 in tracheal aspirates at day 7 were significantly reduced compared with those at baseline or at day 3 posttransplantation. BPD severity was lower in the transplant recipients, and rates of other adverse outcomes did not differ between the comparison group and transplant recipients.
  
  
  CONCLUSIONS
  Intratracheal transplantation of allogeneic hUCB-derived MSCs in preterm infants is safe and feasible, and warrants a larger and controlled phase II study.
authors: Department of Pediatrics, 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.
authors: So Yoon
authors: SY
authors: Ahn
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: Biomedical Research Institute, MEDIPOST Co, Ltd, Seoul, Korea.
authors: Won Il
authors: WI
authors: Oh
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: wonspark@skku.edu.
authors: Won Soon
authors: WS
authors: Park
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016015:Logistic Models; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012720:Severity of Illness Index; D014132:Trachea / Q000378:metabolism / Q000601:surgery; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; C066855:HGF protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor