Document Detail


Human primary bronchial lung cell constructs: the new respiratory models.
MedLine Citation:
PMID:  20403407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Scientists routinely work within the three R's principles of 'Reduction, Refinement and Replacement' of animal experiments. Accordingly, viable alternatives are regularly developed, and in the specific case of the human lung, in vitro models for inhalation toxicology that mimic in vivo toxic events that may occur in the human lung, are welcomed. This is especially warranted given the new EU regulations (i.e. REACH) coming into force for the handling of chemicals and the advent of nanotoxicology. Furthermore, recent advances in human tissue-engineering has made it feasible and cost effective to construct human tissue equivalents of the respiratory epithelia, as in-house models derived from primary cells. There is an urgent need for engineered tissue equivalents of the lung given the increase in pharmaceutically valuable drugs, toxicity testing of environmental pollutants and the advent of nanotoxicology. Given the well-known problems with 2-dimensional (2-D) cell cultures as test beds, more realistic 3-D tissue constructs are required, especially for preclinical stages of cell- and tissue-based, high-throughput screening in drug discovery. The generation of high-fidelity engineered tissue constructs is based on the targeted interactions of organ-specific cells and intelligent biomimetic scaffolds which emulate the natural environment of their native extracellular matrix, in which the cells develop, differentiate and function. The proximal region of the human respiratory system is a critical zone to recapitulate for use as in vitro alternatives to in vivo inhalation toxicology. Undifferentiated normal human bronchial epithelia cells can be obtained from surgical procedures or purchased from commercial sources and used to establish 3-D, differentiated, organo-typic cell cultures for pulmonary research.
Authors:
Kelly Bérubé; Zoë Prytherch; Claire Job; Tracy Hughes
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Publication Detail:
Type:  Journal Article; Review     Date:  2010-04-18
Journal Detail:
Title:  Toxicology     Volume:  278     ISSN:  1879-3185     ISO Abbreviation:  Toxicology     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-01-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  311-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103AX, Wales, UK. berube@cf.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Animal Testing Alternatives
Bronchi / drug effects*,  growth & development
Cells, Cultured
Humans
Models, Biological*
Respiratory Mucosa / drug effects
Respiratory System / anatomy & histology,  cytology
Toxicity Tests / methods*

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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