scholarly journals Neonatal low-density granulocytes internalize and kill bacteria but suppress monocyte function using extracellular DNA

2021 ◽  
pp. jcs.252528
Author(s):  
Brittany G. Seman ◽  
Jordan K. Vance ◽  
Stephen M. Akers ◽  
Cory M. Robinson
Keyword(s):  
Acute Infection ◽  
Mononuclear Phagocytes ◽  
Extracellular Dna ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Low Density ◽  
E Coli ◽  
Host Protection ◽  
Bacterial Uptake ◽  
Inflammatory Cytokine Response

Low-density granulocytes (LDGs) are found abundantly in neonatal blood. However, there is limited mechanistic understanding of LDG interactions with bacteria and innate immune cells during acute infection. We aimed to determine how human neonatal LDGs may influence control of the bacterial burden at sites of infection, both individually and in the presence of mononuclear phagocytes. LDGs from human umbilical cord blood do phagocytose E. coli O1:K1:H7 and traffic bacteria into acidic compartments. However, LDGs were significantly less efficient at bacterial uptake and killing compared to monocytes, and this activity was associated with a reduced inflammatory cytokine response. The presence of bacteria triggered the release of DNA (eDNA) from LDGs into the extracellular space that resembled neutrophil extracellular traps, but had limited anti-bacterial activity. Instead, eDNA significantly impaired monocyte control of bacteria during co-culture. These results suggest that LDG recruitment to sites of bacterial infection may compromise host protection in the neonate. Furthermore, our findings reveal novel insights into LDG activity during infection, clarify inflammatory contributions relative to monocytes, and identify a novel LDG mechanism of immunosuppression.

scholarly journals Neonatal granulocytic MDSCs possess phagocytic properties during bacterial infection

2019 ◽  
Author(s):  
Brittany G. Seman ◽  
Jordan K. Vance ◽  
Michelle R. Witt ◽  
Cory M. Robinson
Keyword(s):  
Bacterial Infection ◽  
Acute Infection ◽  
Suppressor Cells ◽  
Extracellular Dna ◽  
Phagocytic Capacity ◽  
E Coli ◽  
Susceptibility To Infection ◽  
Immunosuppressive Cell ◽  
Gene And Protein Expression ◽  
Bacterial Uptake

AbstractMyeloid-derived suppressor cells (MDSCs) are an immunosuppressive cell type found in high abundance in early life. Currently, there has been limited mechanistic understanding of MDSC phagocytosis of bacteria and the corresponding consequences in the context of acute infection. We set out to determine whether human granulocytic MDSCs have phagocytic capacity that is comparable to other professional phagocytes. To investigate these properties, we utilized fluorescent confocal microscopy, flow cytometry, and bacterial burden assays. We demonstrate that human granulocytic MDSCs phagocytose E. coli O1:K1:H7, and subsequently traffic the bacteria into acidic compartments similar to other phagocytes. However, MDSCs were significantly less efficient at bacterial uptake and killing compared to monocytes. This activity is associated with an inflammatory response, but the amount of TNFα gene and protein expression was reduced in infected MDSCs compared to monocytes. Interestingly, we also found that MDSCs release DNA (MeDNA) into the extracellular space that resembles neutrophil extracellular traps. We found that MeDNA had some impact on bacterial viability in single cultures, with an increase in bacterial recovery in MDSCs treated with DNAse. However, MeDNA did not impact the ability of monocytes to eliminate bacteria in co-cultures, suggesting that MDSC extracellular DNA does not compromise monocyte function. Overall, our data reveals mechanistic insight into MDSC activity during infection that includes the kinetics and efficiency of bacterial uptake, elimination through trafficking to acidified compartments, and inflammatory contributions relative to primary human monocytes. These results enhance our understanding of MDSC contributions during acute bacterial infection and identify host-directed targets for immune intervention to improve outcomes and reduce susceptibility to infection early in life.

scholarly journals Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Xingfu Li ◽  
Li Duan ◽  
Yujie Liang ◽  
Weimin Zhu ◽  
Jianyi Xiong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Expression ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Type I ◽  
Low Density

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs) and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2) and decreased type I collagen (COL1) protein expression levels. SRY-box 9 (SOX9) mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

Therapeutic Potential of Endothelial Colony Forming Cells Derived from Human Umbilical Cord Blood

2019 ◽  
Vol 14 (6) ◽  
pp. 460-465 ◽  
Author(s):  
Jing Jia ◽  
Baitao Ma ◽  
Shaoshuai Wang ◽  
Ling Feng
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Tissue Regeneration ◽  
Umbilical Cord Blood ◽  
Therapeutic Potential ◽  
Human Umbilical Cord Blood ◽  
Proliferative Potential ◽  
Human Umbilical Cord ◽  
Preclinical Studies ◽  
Endothelial Colony Forming Cells

Endothelial progenitor cells (EPCs) are implicated in multiple biologic processes such as vascular homeostasis, neovascularization and tissue regeneration, and tumor angiogenesis. A subtype of EPCs is referred to as endothelial colony-forming cells (ECFCs), which display robust clonal proliferative potential and can form durable and functional blood vessels in animal models. In this review, we provide a brief overview of EPCs’ characteristics, classification and origins, a summary of the progress in preclinical studies with regard to the therapeutic potential of human umbilical cord blood derived ECFCs (CB-ECFCs) for ischemia repair, tissue engineering and tumor, and highlight the necessity to select high proliferative CB-ECFCs and to optimize their recovery and expansion conditions.

Hoechst dye efflux reveals a novel CD7+CD34− lymphoid progenitor in human umbilical cord blood

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2125-2133 ◽  
Author(s):  
Robert W. Storms ◽  
Margaret A. Goodell ◽  
Alan Fisher ◽  
Richard C. Mulligan ◽  
Clay Smith
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Large Population ◽  
Lymphoid Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract A novel Hoechst 33342 dye efflux assay was recently developed that identifies a population of hematopoietic cells termed side population (SP) cells. In the bone marrow of multiple species, including mice and primates, the SP is composed primarily of CD34−cells, yet has many of the functional properties of hematopoietic stem cells (HSCs). This report characterizes SP cells from human umbilical cord blood (UCB). The SP in unfractionated UCB was enriched for CD34+ cells but also contained a large population of CD34− cells, many of which were mature lymphocytes. SP cells isolated from UCB that had been depleted of lineage-committed cells (Lin− UCB) contained CD34+ and CD34− cells in approximately equivalent proportions. Similar to previous descriptions of human HSCs, the CD34+Lin− SP cells were CD38dimHLA-DRdimThy-1dimCD45RA−CD71−and were enriched for myelo-erythroid precursors. In contrast, the CD34−Lin− SP cells were CD38−HLA-DR−Thy-1−CD71−and failed to generate myelo-erythroid progeny in vitro. The majority of these cells were CD7+CD11b+CD45RA+, as might be expected of early lymphoid cells, but did not express other lymphoid markers. The CD7+CD34−Lin− UCB SP cells did not proliferate in simple suspension cultures but did differentiate into natural killer cells when cultured on stroma with various cytokines. In conclusion, the human Lin− UCB SP contains both CD34+ multipotential stem cells and a novel CD7+CD34−Lin− lymphoid progenitor. This observation adds to the growing body of evidence that CD34− progenitors exist in humans.

scholarly journals Endothelial cell precursors are normal components of human umbilical cord blood

1997 ◽  
Vol 98 (3) ◽  
pp. 775-777 ◽  
Author(s):  
Mie Nieda ◽  
Andrew Nicol ◽  
Patricia Denning‐Kendall ◽  
John Sweetenham ◽  
Ben Bradley ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord
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