PMID- 26837282
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20181202
IS  - 1757-9708 (Electronic)
IS  - 1757-9694 (Linking)
VI  - 8
IP  - 2
DP  - 2016 Feb
TI  - Stoichiometric control of live cell mixing to enable fluidically-encoded 
      co-culture models in perfused microbioreactor arrays.
PG  - 194-204
LID - 10.1039/c5ib00311c [doi]
AB  - In vivo, tissues are maintained and repaired through interactions between the 
      present (different) cell types, which communicate with each other through both 
      the secretion of paracrine factors and direct cell-cell contacts. In order to 
      investigate and better understand this dynamic, complex interplay among diverse 
      cell populations, we must develop new in vitro co-culture strategies that enable 
      us to recapitulate such native tissue complexity. In this work, a microfluidic 
      mixer based on a staggered herringbone design was computationally designed and 
      experimentally validated that features the ability to mix large, non-diffusive 
      particles (i.e. live cells) in a programmed manner. This is the first time that 
      the herringbone mixer concept has been shown to effectively mix particles of the 
      size range applicable to live cells. The cell mixer allowed for sequentially 
      mixing of two cell types to generate reverse linear concentration co-culture 
      patterns. Once validated, the mixer was integrated into a perfused 
      microbioreactor array as an upstream module to deliver mixed cells to five 
      downstream culture units, each consisting of ten serially-connected circular 
      microculture chambers. This novel cell mixer microbioreactor array (CM-MBA) 
      platform was validated through the establishment of spatio-temporally tunable 
      osteogenic co-culture models, investigating the role of pre-osteoblastic cells 
      (SAOS2) on human mesenchymal stem cells (hMSCs) commitment to an osteogenic 
      endpoint. An increase on expression of alkaline phosphatase in sequential 
      (downstream) chambers, consistent with the initial linear distribution of SAOS2, 
      suggests not only osteoblastic cell-driven hMSCs induction towards the osteogenic 
      phenotype, but also the importance of paracrine signaling. In conclusion, the 
      cell mixer microbioreactor array combines the ability to rapidly establish cell 
      co-culture models in a high-throughput, programmable fashion, with the additional 
      advantage of maintaining cells in culture under perfused medium to explore 
      paracrine factor impacts, representing a promising new tool for directing 
      multi-cellular tissue formation for tissue engineering applications.
FAU - Occhetta, P
AU  - Occhetta P
AD  - Australian Institute of Bioengineering and Nanotechnology, The University of 
      Queensland, Brisbane, QLD, Australia. j.cooperwhite@uq.edu.au.
FAU - Glass, N
AU  - Glass N
FAU - Otte, E
AU  - Otte E
FAU - Rasponi, M
AU  - Rasponi M
FAU - Cooper-White, J J
AU  - Cooper-White JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160203
PL  - England
TA  - Integr Biol (Camb)
JT  - Integrative biology : quantitative biosciences from nano to macro
JID - 101478378
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - *Bioreactors
MH  - Cell Communication
MH  - Cell Culture Techniques
MH  - Cell Line, Tumor
MH  - *Coculture Techniques
MH  - Diffusion
MH  - Humans
MH  - *Lab-On-A-Chip Devices
MH  - Mesenchymal Stem Cells/cytology
MH  - Mice
MH  - Microfluidic Analytical Techniques
MH  - NIH 3T3 Cells
MH  - Osteoblasts/cytology
MH  - Osteogenesis
MH  - Paracrine Communication
MH  - Phenotype
MH  - Signal Transduction
MH  - Software
MH  - Tissue Engineering/methods
EDAT- 2016/02/04 06:00
MHDA- 2016/12/20 06:00
CRDT- 2016/02/04 06:00
PHST- 2016/02/04 06:00 [entrez]
PHST- 2016/02/04 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
AID - 10.1039/c5ib00311c [doi]
PST - ppublish
SO  - Integr Biol (Camb). 2016 Feb;8(2):194-204. doi: 10.1039/c5ib00311c. Epub 2016 Feb 
      3.