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Stem Cells Dev. 2017 Jul 15;26(14):1054-1064. doi: 10.1089/scd.2016.0329. Epub 2017 May 17.

Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial Clearance in Neonatal Sepsis in Rats.

Author information

1
1 Department of Pediatric Critical Care Medicine, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine , Shanghai, China .
2
2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .
3
3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
4
4 Department of Cellular and Molecular Biology, University of Ottawa , Ontario, Canada .

Abstract

Sepsis is the main cause of morbidity and mortality in neonates. Mesenchymal stromal cells (MSCs) are potent immune-modulatory cells. Their effect in neonatal sepsis has never been explored. We hypothesized that human umbilical cord-derived MSCs (hUC-MSCs) improve survival in experimental neonatal sepsis. Sepsis was induced in 3-day-old rats by intravenous injection of Escherichia coli (5 × 105/rat). One hour after infection, rats were treated intravenously with normal saline, hUC-MSCs, or with interferon-γ preconditioned hUC-MSCs (107 cells/kg). Eighteen hours after infection, survival, bacterial counts, lung neutrophil and macrophage influx, phagocytosis and apoptosis of splenocytes plasma, and LL-37 concentration were evaluated. Animals were observed for survival for 72 h after E. coli injection. Treatment with either hUC-MSCs or preconditioned hUC-MSCs significantly increased survival (hUC-MSCs, 81%; preconditioned hUC-MSCs, 89%; saline, 51%; P < 0.05). Both hUC-MSCs and preconditioned hUC-MSCs enhanced bacterial clearance. Lung neutrophil influx was decreased with preconditioned hUC-MSCs. The number of activated macrophages (CD206+) in the spleen was increased with hUC-MSCs and preconditioned hUC-MSCs; preconditioned hUC-MSCs increased the phagocytic activity of CD206+ macrophages. hUC-MSCs and preconditioned hUC-MSCs decreased splenocyte apoptosis in E. coli infected rats. Finally, LL-37 plasma levels were elevated in neonatal rats treated with hUC-MSCs or preconditioned hUC-MSCs. hUC-MSCs enhance survival and bacterial clearance in experimental neonatal sepsis. hUC-MSCs may be an effective adjunct therapy to reduce neonatal sepsis-related morbidity and mortality.

KEYWORDS:

infection; newborn; sepsis; stem cells; umbilical cord

PMID:
28401804
DOI:
10.1089/scd.2016.0329
[Indexed for MEDLINE]

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