| 1. |
- Hannan, T. J., et al.
(författare)
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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
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| 2. |
- Olausson, Michael, 1956, et al.
(författare)
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In vivo application of tissue-engineered veins using autologous peripheral whole blood: A proof of concept study
- 2014
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 1:1, s. 72-79
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Tidskriftsartikel (refereegranskat)abstract
- Vascular diseases are increasing health problems affecting >25 million individuals in westernized societies. Such patients could benefit fromtransplantation of tissue-engineered vascular grafts using autologous cells. One challenge that has limited this development is the need for cell isolation, and risks associated with ex vivo expanded stem cells. Herewe demonstrate a novel approach to generate transplantable vascular grafts using decellularized allogeneic vascular scaffolds, repopulatedwith peripheralwhole blood (PWB) in vitro in a bioreactor. Circulating, VEGFR-2+/CD45+ and a smaller fraction of VEGFR-2+/CD14+ cells contributed to repopulation of the graft. SEMmicrographs showed flat cells on the luminal surface of the grafts consistentwith endothelial cells. For clinical validation, two autologous PWBtissue-engineered vein conduits were prepared and successfully used for bypass procedures in two pediatric patients. These results provide a proof of principle for the generation of transplantable vascular grafts using a simple autologous blood sample, making it clinically feasible globally.
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