US researchers have developed a fully automated microfluidic cell culture system that can control signalling agents in the extracellular media while maintaining cell viability for weeks.
Cell regulation occurs by numerous signalling mechanisms present in the microenvironment surrounding the cells with the temporal and spatial distribution of these being unique to each development stage and each organ.
New research published in an early access article in the journal Analytical Chemistry , describes the development of a microfluidic cell culture system that maintains cell viability for weeks and enables quantitative measurement of the influence of transient stimulation schedules on the proliferation, differentiation and motility of human mesenchymal stem cells (hMSCs).
While microarrays have enabled research into the effects of extracellular matrix components on cell behaviour, they do not address the effects of intracellular signalling and other soluble cues.
These cues "require time-dependant simulation phenomena to be applied to all environments simultaneously and extracellular factors expressed by cells to diffuse between microenvironments," write the authors from Stanford University, the Howard Hughes Medical Institute and the University of Pennsylvania.
By developing a microfluidic system that can combine the advantages of miniaturarisation and real-time microscopic observation with the ability to better mimic in vivo conditions, more accurate results from drug screening programmes could be produced.
The system enables cell number to be precisely adjusted in each of the devices 96 chambers as well as studying the effects of different mixtures of reagents on the behaviour of cells during long-term culturing.
The researchers demonstrated the ability of the platform to sustain proliferation and differentiation of hMSCs using differentiation media to induce osteogenic and adipogenic differentiation.
In addition, because the system is automated it can precisely control feeding schedules and enabled the researchers to study the effects of media renewal.
They managed to reduce the effects of intracellular paracrine signalling agents to such an extent that cell behaviour depended mainly on the factors provided in the media and not those emitted from the culture.
They also found that cell motility could also be measured using the system, with cells stimulated with osteogenic agents for 96 hours or more exhibiting long term motility differences to those exposed to the agents for shorter periods of time.
"Further study will be required… to determine if there is a casual relationship between the induction of differentiation and decrease in motility of stem cells," write the authors.
By enabling better control of a cell culture system in an automated manner, this device should enable researchers to better understand cell development and intracellular processes, as well as simply enabling greater control over a cells environment to gain more in vivo-like responses to drug candidates.