Matches in SemOpenAlex for { <https://semopenalex.org/work/W2045915548> ?p ?o ?g. }
- W2045915548 endingPage "7168" @default.
- W2045915548 startingPage "7159" @default.
- W2045915548 abstract "The in vivo cellular microenvironment is regulated by a complex interplay of soluble factors and signaling molecules secreted by cells and it plays a critical role in the growth and development of normal and diseased tissues. In vitro systems that can recapitulate the microenvironment at the cellular level are needed to investigate the influence of autocrine signaling and extracellular matrix effects on tissue homeostasis, regeneration, disease development and progression. In this study, we report the use of microbubble technology as a means to culture cells in a controlled microenvironment in which cells can influence their function through autocrine signaling. Microbubbles (MB) are small spherical cavities about 100-300 μm in diameter formed in hydrophobic polydimethylsiloxane (PDMS) with ∼60-100 μm circular openings and aspect ratio ∼3.0. We demonstrate that the unique architecture of the microbubble compartment is advantaged for cell culture using HaCaT cells, an immortalized keratinocyte cell line. We observe that HaCaT cells, seeded in microbubbles (15-20 cells/MB) and cultured under standard conditions, adopt a compact 3D spheroidal morphology. Within 2-3 days, the cells transition to a sheeting morphology. Through experimentation and simulation we show that this transition in morphology is due to the unique architecture of the microbubble compartment which enables cells to condition their local microenvironment. The small media volume per cell and the development of shallow concentration gradients allow factors secreted by the cells to rise to bioactive levels. The kinetics of the morphology transition depends on the number of cells seeded per microbubble; higher cell seeding induces a more rapid transition. HaCaT cells seeded onto PDMS cured in 96-well plates also form compact spheroids but they do not undergo a transition to a sheeting morphology even after several weeks of culture. The importance of soluble factor accumulation in driving this morphology transition in microbubbles is supported by the observation that spheroids do not form when cells - seeded into microbubbles or onto PDMS cured in 96-well plates - are cultured in media conditioned by HaCaT cells grown in standard tissue culture plate. We observed that the addition of TGF-β1 to the growth media induced cells to proliferate in a sheeting morphology from the onset both on PDMS cured in 96-well plates and in microbubbles. TGF-β1 is a morphogen known to regulate epithelial-to-mesenchymal transition (EMT). Studies of the role of Ca(2+) concentration and changes in E-cadherin expression additionally support an EMT-like HaCaT morphology transition. These findings taken together validate the microbubble compartment as a unique cell culture platform that can potentially transform investigative studies in cell biology and in particular the tumor microenvironment. Targeting the tumor microenvironment is an emerging area of anti-cancer therapy." @default.
- W2045915548 created "2016-06-24" @default.
- W2045915548 creator A5046827479 @default.
- W2045915548 creator A5052894284 @default.
- W2045915548 creator A5081005464 @default.
- W2045915548 creator A5085492763 @default.
- W2045915548 date "2011-10-01" @default.
- W2045915548 modified "2023-10-18" @default.
- W2045915548 title "Microenvironment induced spheroid to sheeting transition of immortalized human keratinocytes (HaCaT) cultured in microbubbles formed in polydimethylsiloxane" @default.
- W2045915548 cites W1760215417 @default.
- W2045915548 cites W1876434939 @default.
- W2045915548 cites W1966929586 @default.
- W2045915548 cites W1969375579 @default.
- W2045915548 cites W1969396578 @default.
- W2045915548 cites W1981684516 @default.
- W2045915548 cites W1982220375 @default.
- W2045915548 cites W1993497779 @default.
- W2045915548 cites W1993653794 @default.
- W2045915548 cites W1995044247 @default.
- W2045915548 cites W1996775799 @default.
- W2045915548 cites W2000196225 @default.
- W2045915548 cites W2010251891 @default.
- W2045915548 cites W2013240219 @default.
- W2045915548 cites W2017656225 @default.
- W2045915548 cites W2019866887 @default.
- W2045915548 cites W2027167730 @default.
- W2045915548 cites W2030450624 @default.
- W2045915548 cites W2030509793 @default.
- W2045915548 cites W2031036670 @default.
- W2045915548 cites W2033087883 @default.
- W2045915548 cites W2041585886 @default.
- W2045915548 cites W2041612826 @default.
- W2045915548 cites W2043156676 @default.
- W2045915548 cites W2044980878 @default.
- W2045915548 cites W2045394733 @default.
- W2045915548 cites W2045498586 @default.
- W2045915548 cites W2047707023 @default.
- W2045915548 cites W2061631105 @default.
- W2045915548 cites W2062239595 @default.
- W2045915548 cites W2070384392 @default.
- W2045915548 cites W2071628173 @default.
- W2045915548 cites W2084205277 @default.
- W2045915548 cites W2095634203 @default.
- W2045915548 cites W2096827237 @default.
- W2045915548 cites W2101167135 @default.
- W2045915548 cites W2104208190 @default.
- W2045915548 cites W2108404067 @default.
- W2045915548 cites W2112787985 @default.
- W2045915548 cites W2114662808 @default.
- W2045915548 cites W2116333900 @default.
- W2045915548 cites W2125921526 @default.
- W2045915548 cites W2126882378 @default.
- W2045915548 cites W2136280424 @default.
- W2045915548 cites W2138312252 @default.
- W2045915548 cites W2148328056 @default.
- W2045915548 cites W2150739149 @default.
- W2045915548 cites W2154589460 @default.
- W2045915548 cites W2165673443 @default.
- W2045915548 cites W2168607632 @default.
- W2045915548 cites W2172083228 @default.
- W2045915548 cites W4255760236 @default.
- W2045915548 doi "https://doi.org/10.1016/j.biomaterials.2011.06.013" @default.
- W2045915548 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3148275" @default.
- W2045915548 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21724250" @default.
- W2045915548 hasPublicationYear "2011" @default.
- W2045915548 type Work @default.
- W2045915548 sameAs 2045915548 @default.
- W2045915548 citedByCount "33" @default.
- W2045915548 countsByYear W20459155482012 @default.
- W2045915548 countsByYear W20459155482013 @default.
- W2045915548 countsByYear W20459155482014 @default.
- W2045915548 countsByYear W20459155482015 @default.
- W2045915548 countsByYear W20459155482016 @default.
- W2045915548 countsByYear W20459155482017 @default.
- W2045915548 countsByYear W20459155482018 @default.
- W2045915548 countsByYear W20459155482019 @default.
- W2045915548 countsByYear W20459155482020 @default.
- W2045915548 countsByYear W20459155482021 @default.
- W2045915548 countsByYear W20459155482023 @default.
- W2045915548 crossrefType "journal-article" @default.
- W2045915548 hasAuthorship W2045915548A5046827479 @default.
- W2045915548 hasAuthorship W2045915548A5052894284 @default.
- W2045915548 hasAuthorship W2045915548A5081005464 @default.
- W2045915548 hasAuthorship W2045915548A5085492763 @default.
- W2045915548 hasBestOaLocation W20459155482 @default.
- W2045915548 hasConcept C118995209 @default.
- W2045915548 hasConcept C12554922 @default.
- W2045915548 hasConcept C128240485 @default.
- W2045915548 hasConcept C163688615 @default.
- W2045915548 hasConcept C170493617 @default.
- W2045915548 hasConcept C171250308 @default.
- W2045915548 hasConcept C175369904 @default.
- W2045915548 hasConcept C185592680 @default.
- W2045915548 hasConcept C189165786 @default.
- W2045915548 hasConcept C192562407 @default.
- W2045915548 hasConcept C2779849746 @default.
- W2045915548 hasConcept C54355233 @default.
- W2045915548 hasConcept C55493867 @default.