Decision letter for "Ex Vivo Organ Cultures as Models to Study Bone Biology"

Keyword(s):  
Ex Vivo ◽  
JBMR Plus ◽  
2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Teresita Bellido ◽  
Jesus Delgado‐Calle
Keyword(s):  
Ex Vivo ◽  

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3197-3206 ◽  
Author(s):  
Agatha Kokot ◽  
Dieter Metze ◽  
Nicolas Mouchet ◽  
Marie-Dominique Galibert ◽  
Meinhard Schiller ◽  
...  

Human skin is constantly exposed to UV light, the most ubiquitous environmental stressor. Here, we investigated the expression and regulation of Nrf1-3, transcription factors crucially involved in protection against oxidative stress in human skin cells in vitro, ex vivo, and in situ. In particular, we examined whether α-MSH, a UV-induced peptide, is capable of modulating Nrf2 and Nrf-dependent gene expression. Nrf1, -2, and -3 were found to be expressed in various cutaneous cell types in vitro. Surprisingly, UVB irradiation at physiological doses (10 mJ/cm2) reduced Nrf2 and Nrf-dependent gene expression in normal keratinocytes and melanocytes in vitro as well as ex vivo in skin organ cultures. α-MSH alone significantly increased Nrf2 as well as Nrf-dependent heme oxygenase-1, γ-glutamylcysteine-synthetase, and glutathione-S-transferase Pi gene expression in both keratinocytes and melanocytes. This effect of α-MSH occurred at physiological doses and was due to transcriptional induction, mimicked by the artificial cAMP inducer forskolin, and blocked by protein kinase A pathway inhibition. In silico promoter analysis of Nrf2 further identified several putative binding sites for activator protein 1 and cAMP response element-binding protein, transcription factors typically activated by α-MSH. Importantly, α-MSH prevented or even overcompensated the UVB-induced suppression of Nrf2 and Nrf-dependent genes not only in normal keratinocytes and melanocytes in vitro but also in skin organ cultures. These findings, for the first time, show regulation of Nrf2 and Nrf-dependent genes by α-MSH. Our data also highlight a novel facet in the cytoprotective and antioxidative effector mechanisms of α-MSH and perhaps of related melanocortin peptides.


2021 ◽  
Vol 250 ◽  
pp. 01024
Author(s):  
Benjamin Butler ◽  
Thuy-Tien Nguyen ◽  
Alun Williams ◽  
Andrew Tucker ◽  
William G. Proud ◽  
...  

War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).


mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Jeffrey M. Grabowski ◽  
Konstantin A. Tsetsarkin ◽  
Dan Long ◽  
Dana P. Scott ◽  
Rebecca Rosenke ◽  
...  

ABSTRACT Ixodes scapularis ticks transmit many infectious agents that cause disease, including tick-borne flaviviruses (TBFVs). TBFV infections cause thousands of human encephalitis cases worldwide annually. In the United States, human TBFV infections with Powassan virus (POWV) are increasing and have a fatality rate of 10 to 30%. Additionally, Langat virus (LGTV) is a TBFV of low neurovirulence and is used as a model TBFV. TBFV replication and dissemination within I. scapularis organs are poorly characterized, and a deeper understanding of virus biology in this vector may inform effective countermeasures to reduce TBFV transmission. Here, we describe short-term, I. scapularis organ culture models of TBFV infection. Ex vivo organs were metabolically active for 9 to 10 days and were permissive to LGTV and POWV replication. Imaging and videography demonstrated replication and spread of green fluorescent protein-expressing LGTV in the organs. Immunohistochemical staining confirmed LGTV envelope and POWV protein synthesis within the infected organs. LGTV- and POWV-infected organs produced infectious LGTV and POWV; thus, the ex vivo cultures were suitable for study of virus replication in individual organs. LGTV- and POWV-infected midgut and salivary glands were subjected to double-stranded RNA (dsRNA) transfection with dsRNA to the LGTV 3′ untranslated region (UTR), which reduced infectious LGTV and POWV replication, providing a proof-of-concept use of RNA interference in I. scapularis organ cultures to study the effects on TBFV replication. The results contribute important information on TBFV localization within ex vivo I. scapularis organs and provide a significant translational tool for evaluating recombinant, live vaccine candidates and potential tick transcripts and proteins for possible therapeutic use and vaccine development to reduce TBFV transmission. IMPORTANCE Tick-borne flavivirus (TBFV) infections cause neurological and/or hemorrhagic disease in humans worldwide. There are currently no licensed therapeutics or vaccines against Powassan virus (POWV), the only TBFV known to circulate in North America. Evaluating tick vector targets for antitick vaccines directed at reducing TBFV infection within the arthropod vector is a critical step in identifying efficient approaches to controlling TBFV transmission. This study characterized infection of female Ixodes scapularis tick organ cultures of midgut, salivary glands, and synganglion with the low-neurovirulence Langat virus (LGTV) and the more pathogenic POWV. Cell types of specific organs were susceptible to TBFV infection, and a difference in LGTV and POWV replication was noted in TBFV-infected organs. This tick organ culture model of TBFV infection will be useful for various applications, such as screening of tick endogenous dsRNA corresponding to potential control targets within midgut and salivary glands to confirm restriction of TBFV infection.


2013 ◽  
Vol 87 (12) ◽  
pp. 6604-6614 ◽  
Author(s):  
R. W. Y. Chan ◽  
M. C. W. Chan ◽  
S. Agnihothram ◽  
L. L. Y. Chan ◽  
D. I. T. Kuok ◽  
...  

2018 ◽  
Vol 4 (3) ◽  
pp. 247-256 ◽  
Author(s):  
Jeffrey M. Grabowski ◽  
Danielle K. Offerdahl ◽  
Marshall E. Bloom

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