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J Inflamm Res. 2014 Dec 31;8:1-8. doi: 10.2147/JIR.S71987. eCollection 2015.

Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils.

Author information

1
Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
2
Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USA.
3
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.

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.

CONCLUSION:

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.

KEYWORDS:

apoptosis; inflammation; mesenchymal stem cells; neutrophil; umbilical cord

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