Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils
Imteyaz Khan,1 Liying Zhang,2 Moiz Mohammed,1 Faith E Archer,1 Jehan Abukharmah,1 Zengrong Yuan,2 S Saif Rizvi,1 Michael G Melek,1 Arnold B Rabson,1,2 Yufang Shi,2 Barry Weinberger,1 Anna M Vetrano1,21Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, 2Ru...
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Dove Medical Press
2014
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oai:doaj.org-article:ade0be8f4b6b4999b5420c09df0bb5942021-12-02T02:32:02ZEffects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils1178-7031https://doaj.org/article/ade0be8f4b6b4999b5420c09df0bb5942014-12-01T00:00:00Zhttp://www.dovepress.com/effects-of-wharton39s-jelly-derived-mesenchymal-stem-cells-on-neonatal-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031 Imteyaz Khan,1 Liying Zhang,2 Moiz Mohammed,1 Faith E Archer,1 Jehan Abukharmah,1 Zengrong Yuan,2 S Saif Rizvi,1 Michael G Melek,1 Arnold B Rabson,1,2 Yufang Shi,2 Barry Weinberger,1 Anna M Vetrano1,21Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, 2Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USABackground: 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: inflammation, umbilical cord, apoptosis, neutrophil, mesenchymal stem cellsKhan IZhang LMohammed MArcher FEAbukharmah JYuan ZRizvi SSMelek MGRabson ABShi YWeinberger BVetrano AMDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2015, Iss default, Pp 1-8 (2014) |
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DOAJ |
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Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Khan I Zhang L Mohammed M Archer FE Abukharmah J Yuan Z Rizvi SS Melek MG Rabson AB Shi Y Weinberger B Vetrano AM Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| description |
Imteyaz Khan,1 Liying Zhang,2 Moiz Mohammed,1 Faith E Archer,1 Jehan Abukharmah,1 Zengrong Yuan,2 S Saif Rizvi,1 Michael G Melek,1 Arnold B Rabson,1,2 Yufang Shi,2 Barry Weinberger,1 Anna M Vetrano1,21Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, 2Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USABackground: 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: inflammation, umbilical cord, apoptosis, neutrophil, mesenchymal stem cells |
| format |
article |
| author |
Khan I Zhang L Mohammed M Archer FE Abukharmah J Yuan Z Rizvi SS Melek MG Rabson AB Shi Y Weinberger B Vetrano AM |
| author_facet |
Khan I Zhang L Mohammed M Archer FE Abukharmah J Yuan Z Rizvi SS Melek MG Rabson AB Shi Y Weinberger B Vetrano AM |
| author_sort |
Khan I |
| title |
Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| title_short |
Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| title_full |
Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| title_fullStr |
Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| title_full_unstemmed |
Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| title_sort |
effects of wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils |
| publisher |
Dove Medical Press |
| publishDate |
2014 |
| url |
https://doaj.org/article/ade0be8f4b6b4999b5420c09df0bb594 |
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