title: Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial Clearance in Neonatal Sepsis in Rats.
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 (107cells/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.
authors.affiliation: 1 Department of Pediatric Critical Care Medicine, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine , Shanghai, China .|2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Yueniu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Liqun
authors.initials: L
authors.lastname: Xu
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .|4 Department of Cellular and Molecular Biology, University of Ottawa , Ontario, Canada .
authors.forename: Jennifer J P
authors.initials: JJP
authors.lastname: Collins
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Arul
authors.initials: A
authors.lastname: Vadivel
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Chanèle
authors.initials: C
authors.lastname: Cyr-Depauw
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Shumei
authors.initials: S
authors.lastname: Zhong
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Lars
authors.initials: L
authors.lastname: Mense
authors.affiliation: 3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .
authors.forename: Marius A
authors.initials: MA
authors.lastname: Möbius
authors.affiliation: 2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .|3 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute (OHRI) , Ottawa, Ontario, Canada .|4 Department of Cellular and Molecular Biology, University of Ottawa , Ontario, Canada .
authors.forename: Bernard
authors.initials: B
authors.lastname: Thébaud
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000097:blood; D004926:Escherichia coli / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D000071074:Neonatal Sepsis / Q000097:blood / Q000382:microbiology* / Q000628:therapy*; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D051381:Rats; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins
keywords: infection; newborn; sepsis; stem cells; umbilical cord