Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep

2012 ◽  
Vol 206 (5) ◽  
pp. 448.e8-448.e15 ◽  
Author(s):  
Ryan J. Hodges ◽  
Graham Jenkin ◽  
Stuart B. Hooper ◽  
Beth Allison ◽  
Rebecca Lim ◽  
...  
2017 ◽  
Vol 8 ◽  
Author(s):  
Alana Westover ◽  
Jacqueline M. Melville ◽  
Courtney McDonald ◽  
Rebecca Lim ◽  
Graham Jenkin ◽  
...  

2017 ◽  
Vol 26 (4) ◽  
pp. 541-553 ◽  
Author(s):  
Tamara Yawno ◽  
Tharani Sabaretnam ◽  
Jingang Li ◽  
Courtney Mcdonald ◽  
Rebecca Lim ◽  
...  

Intrauterine inflammation is a significant cause of injury to the developing fetal brain. Using a preterm fetal sheep model of in utero infection, we asked whether human amnion epithelial cells (hAECs) were able to reduce inflammation-induced fetal brain injury. Surgery was undertaken on pregnant sheep at ~105 days gestation (term is 147 days) for implantation of vascular catheters. Lipopolysaccharide (LPS; 150 ng/kg bolus) or saline was administered IV at 109, 110, and 111 days. Sixty million fluorescent-labeled hAECs were administered at 110, 111, and 112 days gestation via the brachial artery catheter. Brains were collected at 114 days for histological assessment. hAECs were observed within the cortex, white matter, and hippocampus. Compared to control lambs, LPS administration was associated with significant and widespread fetal brain inflammation and injury as evidenced by increased number of activated microglia in the periventricular white matter ( p = 0.02), increased pyknosis, cell degeneration ( p = 0.01), and a nonsignificant trend of fewer oligodendrocytes in the subcortical and periventricular white matter. Administration of hAECs to LPS-treated animals was associated with a significant mitigation in both inflammation and injury as evidenced by fewer activated microglia ( p = 0.03) and pyknotic cells ( p = 0.03), significantly more oligodendrocytes in the subcortical and periventricular white matter ( p = 0.01 and 0.02, respectively), and more myelin basic protein-positive cells within the periventricular white matter ( p = 0.02). hAEC administration to fetal sheep exposed to multiple doses of LPS dampens the resultant fetal inflammatory response and mitigates associated brain injury.


2011 ◽  
Vol 20 (6) ◽  
pp. 909-924 ◽  
Author(s):  
Sean Murphy ◽  
Rebecca Lim ◽  
Hayley Dickinson ◽  
Rutu Acharya ◽  
Sharina Rosli ◽  
...  

2013 ◽  
Vol 22 (8) ◽  
pp. 1337-1349 ◽  
Author(s):  
Patricia Vosdoganes ◽  
Euan M. Wallace ◽  
Siow Teng Chan ◽  
Rutu Acharya ◽  
Tim J. M. Moss ◽  
...  

2017 ◽  
Vol 39 (2) ◽  
pp. 223-239 ◽  
Author(s):  
Lotte G van den Heuij ◽  
Mhoyra Fraser ◽  
Suzanne L Miller ◽  
Graham Jenkin ◽  
Euan M Wallace ◽  
...  

Perinatal hypoxic-ischemic (HI) brain injury remains highly associated with neurodevelopmental disability after preterm birth. There is increasing evidence that disability is linked with impaired white matter maturation, but there is no specific treatment. In this study, we evaluated whether, in preterm fetal sheep, delayed intranasal infusion of human amnion epithelial cells (hAECs) given 1, 3 and 10 days after severe HI, induced by umbilical cord occlusion for 25 min, can restore white matter maturation or reduce delayed cell loss. After 21 days recovery, asphyxia was associated with reduced electroencephalographic (EEG) maturation, brain weight and cortical area, impaired maturation of oligodendrocytes (OLs), no significant loss of total OLs but a marked reduction in immature/mature OLs and reduced myelination. Intranasal infusion of hAECs was associated with improved brain weight and restoration of immature/mature OLs and fractional area of myelin basic protein, with reduced microglia and astrogliosis. Cortical EEG frequency distribution was partially improved, with reduced loss of cortical area, and attenuated cleaved-caspase-3 expression and microgliosis. Neuronal survival in deep grey matter nuclei was improved, with reduced microglia, astrogliosis and cleaved-caspase-3-positive apoptosis. These findings suggest that delayed intranasal hAEC administration has potential to alleviate chronic dysmaturation after perinatal HI.


2011 ◽  
Vol 205 (2) ◽  
pp. 156.e26-156.e33 ◽  
Author(s):  
Patricia Vosdoganes ◽  
Ryan J. Hodges ◽  
Rebecca Lim ◽  
Alana J. Westover ◽  
Rutu Y. Acharya ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Dandan Zhu ◽  
Ruth Muljadi ◽  
Siow Teng Chan ◽  
Patricia Vosdoganes ◽  
Camden Lo ◽  
...  

The effects of human amnion epithelial cells (hAECs) on angiogenesis remain controversial. It is yet unknown if the presence of inflammation and/or gestational age of hAEC donors have an impact on angiogenesis. In this study, we examined the differences between term and preterm hAECs on angiogenesisin vitroandin vivo. Conditioned media from term hAECs induced the formation of longer huVEC tubules on Matrigel. Both term and preterm hAECs expressedVEGFA,PDGFB, ANGPT1,andFOXC1, which significantly increased after TNFαand IFNγstimulation. In the presence of TNFαand IFNγ, coculture with term hAECs reduced gene transcription ofTie-2andFoxc1in huVECs, while coculture with preterm hAECs increased gene transcription ofPDGFRαandPDGFRβand reduced gene transcription ofFOXC1in huVECs.In vivoassessment of angiogenesis using vWF immunostaining revealed that hAEC treatment decreased angiogenesis in a bleomycin model of lung fibrosis but increased angiogenesis in a neonatal model of hyperoxia-induced lung injury. In summary, our findings suggested that the impact of hAECs on angiogenesis may be influenced by the presence of inflammation and underlying pathology.


Cytotherapy ◽  
2013 ◽  
Vol 15 (8) ◽  
pp. 1021-1029 ◽  
Author(s):  
Patricia Vosdoganes ◽  
Rebecca Lim ◽  
Eugenia Koulaeva ◽  
Siow Teng Chan ◽  
Rutu Acharya ◽  
...  

1995 ◽  
Vol 52 (4) ◽  
pp. 839-847 ◽  
Author(s):  
Catherine A. Jones ◽  
Keryn A. Williams ◽  
John J. Finlay-Jones ◽  
Prue H. Hart

2010 ◽  
Vol 19 (9) ◽  
pp. 1157-1168 ◽  
Author(s):  
Ursula Manuelpillai ◽  
Jorge Tchongue ◽  
Dinushka Lourensz ◽  
Vijesh Vaghjiani ◽  
Chrishan S. Samuel ◽  
...  

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