Center for Experimental Medicine

Medicine, Ireland

Center for Experimental Medicine

Medicine, Ireland
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Jackson M.V.,Center for Experimental Medicine | Morrison T.J.,Center for Experimental Medicine | Doherty D.F.,Center for Experimental Medicine | Mcauley D.F.,Center for Experimental Medicine | And 3 more authors.
Stem Cells | Year: 2016

Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct coculture of MSC with monocyte-derived macrophages enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through tunneling nanotubes (TNT)-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the antimicrobial effect of MSC in vivo. Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the antimicrobial effect of MSC in ARDS. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.


Schuck O.,Transplant Center | Teplan V.,Transplant Center | Franekova J.,Specialized Laboratory of Biochemistry | Malinska H.,Center for Experimental Medicine | And 4 more authors.
Clinical Nephrology | Year: 2014

It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution. © 2014 Dustri-Verlag Dr. K. Feistle.


Calpe S.,Center for Experimental Medicine | Compare D.,University of Naples Federico II | Mari L.,Center for Experimental Medicine | Nardone G.,University of Naples Federico II | Parikh K.,Center for Experimental Medicine
Annals of the New York Academy of Sciences | Year: 2014

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on signaling pathways that can be targeted with immunotherapy; the role of micro-RNAs in the immune response to esophageal cancer; and the association between obesity, the immune system, and esophageal adenocarcinoma. © 2014 New York Academy of Sciences.


Nowacka M.M.,Medical University of Silesia, Katowice | Nowacka M.M.,Academy of Physical Education in Katowice | Nowacka M.M.,Center For Experimental Medicine | Paul-Samojedny M.,Medical University of Silesia, Katowice | And 2 more authors.
Neuroscience Research | Year: 2014

The aim of the present study was to estimate the influence of antidepressants given chronically on brain-derived neurotrophic factor (BDNF) alterations induced by lipopolysaccharide (LPS) in the amygdala and hippocampus of female rats subjected to chronic social instability stress (CSIS) for 29-30 days. CSIS was used as a paradigm known to be more stressful for females because stress induces affective disorders more frequently in women than men. An increased relative adrenal weight and a tendency towards the enhanced plasma corticosterone concentration were found in the stressed rats. Sucrose preference was not changed. On the last experimental day, the rats in the estrus phase were injected ip with LPS (1. mg/kg). In the stressed rats, LPS administration decreased BDNF mRNA levels in both limbic structures. Desipramine (10. mg/kg), fluoxetine (5. mg/kg) or tianeptine (10. mg/kg) given ip once daily reversed the effect of the combined stress and LPS, and tianeptine induced the strongest effects. These results indicate that chronic stress enhances vulnerability of BDNF response to deleterious influence of neuroinflammation in the examined limbic structures, what may account for its role in triggering neuropsychiatric diseases. The observed effect of antidepressants may be of significance for their therapeutic effects in the stress-induced affective disorders in females. © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society.


Deng H.,Center for Experimental Medicine | Deng H.,Central South University | Tan T.,Center for Experimental Medicine
Current Genomics | Year: 2015

Syndactyly, webbing of adjacent digits with or without bony fusion, is one of the most common hereditary limb malformations. It occurs either as an isolated abnormality or as a component of more than 300 syndromic anomalies. There are currently nine types of phenotypically diverse non- syndromic syndactyly. Non-syndromic syndactyly is usually inherited as an autosomal dominant trait, although the more severe presenting types and subtypes may show autosomal recessive or X-linked pattern of inheritance. The phenotype appears to be not only caused by a main gene, but also depend- n_ Deng ant on genetic background and subsequent signaling pathways involved in limb formation. So far, the principal genes identified to be involved in congenital syndactyly are mainly involved in the zone of polarizing activity and sonic hedgehog pathway. This review summarizes the recent progress made in the molecular genetics, including known genes and loci responsible for non-syndromic syndactyly, and the signaling pathways those genetic factors involved in, as well as clinical features and animal models. We hope our review will contribute to the understanding of underlying pathogenesis of this complicated disorder and have implication on genetic counseling. © 2015 Bentham Science Publishers


PubMed | Center for Experimental Medicine
Type: | Journal: Annals of the New York Academy of Sciences | Year: 2014

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on signaling pathways that can be targeted with immunotherapy; the role of micro-RNAs in the immune response to esophageal cancer; and the association between obesity, the immune system, and esophageal adenocarcinoma.


PubMed | Center for Experimental Medicine and Central South University
Type: Journal Article | Journal: Current genomics | Year: 2015

Syndactyly, webbing of adjacent digits with or without bony fusion, is one of the most common hereditary limb malformations. It occurs either as an isolated abnormality or as a component of more than 300 syndromic anomalies. There are currently nine types of phenotypically diverse nonsyndromic syndactyly. Non-syndromic syndactyly is usually inherited as an autosomal dominant trait, although the more severe presenting types and subtypes may show autosomal recessive or X-linked pattern of inheritance. The phenotype appears to be not only caused by a main gene, but also dependant on genetic background and subsequent signaling pathways involved in limb formation. So far, the principal genes identified to be involved in congenital syndactyly are mainly involved in the zone of polarizing activity and sonic hedgehog pathway. This review summarizes the recent progress made in the molecular genetics, including known genes and loci responsible for non-syndromic syndactyly, and the signaling pathways those genetic factors involved in, as well as clinical features and animal models. We hope our review will contribute to the understanding of underlying pathogenesis of this complicated disorder and have implication on genetic counseling.

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