Microfluidics can control how stem cells communicate

A-B. Microfluidic perfusion device. C. Microfluidic perfusion systems use flow to fine-tune the relative significance of convection, diffusion, and reaction.

Exciting to see the work of Dr. Katarina Blagovic from the Voldman group at MIT published in PLoS ONE last month: “Microfluidic Perfusion for Regulating Diffusible Signaling in Stem Cells.” Katarina continued and extended the work begun during my Ph.D. (I’m a co-author), and it’s wonderful to see the ideas we discussed become reality!

In diffusible signaling, cells communicate with each other by secreting signaling molecules which diffuse into the surrounding liquid before being taken up by those same cells or neighboring cells via receptors. Cell signaling is especially important for stem cells because it can determine how a stem cell specializes into various tissue types. Traditionally cells are grown in Petri dishes in standing liquid. In these conditions, the chemical makeup of the environment around the cells is constantly changing as cells secrete and take up a complex array of signaling molecules. It has been challenging for biologists to experimentally probe the details of these closed-loop interactions: what molecules are secreted when, which cells receive the signals, and what effects do the signals have on the cell?

Enter microfluidics. This paper shows how microfluidics provide a new tool for biologists to interrogate diffusible signaling loops. The idea: for cells grown under continuous, non-recirculating microfluidic perfusion, most secreted signaling molecules are swept away before binding to nearby cells. This continuous clearing enables more strict control over the cell’s environment by allowing the researcher to specify what molecules are perfused into the cell culture. In engineering terms, you have more control over the inputs (signaling molecules) to the system (the cell).

Not only did Katarina show that continuous flow can disrupt diffusible signaling, she was able to uncover a specific biological result which suggests that FGF4 is not the only cell-secreted molecule needed for differentiation of the stem cells to neuroectoderm (cells that gives rise to our nervous system during development).

On the commercial front, CellASIC, a company spun out of Luke Lee’s lab at Berkeley, has created a series of products to support microfluidic perfusion culture. And Fluidigm is developing a stem cell culture chip.

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