title: Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton's jelly (WJ-MSCs) are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known. We compared the effects of WJ-MSCs on apoptosis and the expression of inflammatory, oxidant, and antioxidant mediators in adult and neonatal neutrophils.
  
  
  METHODS
  WJ-MSCs were isolated, and their purity and function were confirmed by flow cytometry. Neutrophils were isolated from cord and adult blood by density centrifugation. The effects of neutrophil/WJ-MSC co-culture on apoptosis and gene and protein expression were measured.
  
  
  RESULTS
  WJ-MSCs suppressed neutrophil apoptosis in a dose-dependent manner. WJ-MSCs decreased gene expression of NADPH oxidase-1 in both adult and neonatal neutrophils, but decreased heme oxygenase-1 and vascular endothelial growth factor and increased catalase and cyclooxygenase-2 in the presence of lipopolysaccharide only in adult cells. Similarly, generation of interleukin-8 was suppressed in adult but not neonatal neutrophils. Thus, WJ-MSCs dampened oxidative, vascular, and inflammatory activity by adult neutrophils, but neonatal neutrophils were less responsive. Conversely, Toll-like receptor-4, and cyclooxygenase-2 were upregulated in WJ-MSCs only in the presence of adult neutrophils, suggesting an inflammatory MSC phenotype that is not induced by neonatal neutrophils.
  
  
  CONCLUSIONS
  Whereas WJ-MSCs altered gene expression in adult neutrophils in ways suggesting anti-inflammatory and antioxidant effects, these responses were attenuated in neonatal cells. In contrast, inflammatory gene expression in WJ-MSCs was increased in the presence of adult but not neonatal neutrophils. These effects should be considered in clinical trial design before WJ-MSC-based therapy is used in infants.
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Imteyaz
authors: I
authors: Khan
authors: Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USA.
authors: Liying
authors: L
authors: Zhang
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Moiz
authors: M
authors: Mohammed
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Faith E
authors: FE
authors: Archer
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Jehan
authors: J
authors: Abukharmah
authors: Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USA.
authors: Zengrong
authors: Z
authors: Yuan
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: S Saif
authors: SS
authors: Rizvi
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Michael G
authors: MG
authors: Melek
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA ; Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USA.
authors: Arnold B
authors: AB
authors: Rabson
authors: Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USA.
authors: Yufang
authors: Y
authors: Shi
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Barry
authors: B
authors: Weinberger
authors: Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA ; Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USA.
authors: Anna M
authors: AM
authors: Vetrano
keywords: apoptosis; inflammation; mesenchymal stem cells; neutrophil; umbilical cord