Document Detail

Thick-tissue bioreactor as a platform for long-term organotypic culture and drug delivery.
MedLine Citation:
PMID:  22964798     Owner:  NLM     Status:  MEDLINE    
We have developed a novel, portable, gravity-fed, microfluidics-based platform suitable for optical interrogation of long-term organotypic cell culture. This system is designed to provide convenient control of cell maintenance, nutrients, and experimental reagent delivery to tissue-like cell densities housed in a transparent, low-volume microenvironment. To demonstrate the ability of our Thick-Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density cellular arrays, we observed the morphogenic growth of human mammary epithelial cell lines, MCF-10A and their invasive variants, cultured under three-dimensional (3D) conditions inside our system. Over the course of 21 days, these cells typically develop into hollow "mammospheres" if cultured in standard 3D Matrigel. This complex morphogenic process requires alterations in a variety of cellular functions, including degradation of extracellular matrix that is regulated by cell-produced matrix proteinases. For our "drug" delivery testing and validation experiments we have introduced proteinase inhibitors into the fluid supply system, and we observed both reduced proteinase activity and inhibited cellular morphogenesis. The size inhibition results correlated well with the overall proteinase activities of the tested cells.
Dmitry A Markov; Jenny Q Lu; Philip C Samson; John P Wikswo; Lisa J McCawley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Lab on a chip     Volume:  12     ISSN:  1473-0189     ISO Abbreviation:  Lab Chip     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-25     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  101128948     Medline TA:  Lab Chip     Country:  England    
Other Details:
Languages:  eng     Pagination:  4560-8     Citation Subset:  IM    
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MeSH Terms
Cell Culture Techniques / instrumentation,  methods*
Cells, Cultured
Drug Delivery Systems*
Epithelial Cells / drug effects*,  enzymology
Equipment Design
Microfluidic Analytical Techniques / instrumentation,  methods*
Peptide Hydrolases / metabolism
Protease Inhibitors / pharmacology*
Structure-Activity Relationship
Taxoids / pharmacology
Grant Support
Reg. No./Substance:
0/Protease Inhibitors; 0/Taxoids; 15H5577CQD/docetaxel; EC 3.4.-/Peptide Hydrolases

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

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