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

• Published in: Journal of inflammation research 2015-01, Vol.8 (default), p.1-8
• Main Authors: Khan, Imteyaz, Zhang, Liying, Mohammed, Moiz, Archer, Faith E, Abukharmah, Jehan, Yuan, Zengrong, Rizvi, S Saif, Melek, Michael G, Rabson, Arnold B, Shi, Yufang, Weinberger, Barry, Vetrano, Anna M
• Format: Article
• Language: English
• Subjects: Antioxidants; Apoptosis; Bone marrow; Care and treatment; Cell adhesion & migration; Chemokines; Comparative analysis; Cytokines; Experiments; Flow cytometry; Gene expression; Health aspects; Infants (Newborn); inflammation; Inflammatory diseases; Lipopolysaccharides; Mesenchymal stem cells; neutrophil; Neutrophils; Newborn babies; Original Research; Oxidases; Sepsis; Stem cells; Toll-like receptors; Umbilical cord; Vascular endothelial growth factor
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S71987

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. 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. 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. 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.