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The World Is Not Flat: Exploring Cells and Tissues in Three Dimensions

The cells and tissues in our bodies grow, develop and interact in a highly complex, three-dimensional world. Likewise, the various microbial pathogens that invade our bodies and cause infectious disease interact with this complex 3-D tissue milieu. Yet the methods of culturing and studying human cells have traditionally been carried out in two dimensions on flat impermeable surfaces. While such 2-D culturing and modeling efforts have produced a steady stream of critical insight into cell behavior and the mechanisms of infection and disease, 2-D cell cultures have key limitations in terms of accurately reproducing the tissue environment in vivo, that is, the environment found within a living organism.

In the current issue of the journal Nature Reviews Microbiology, researcher Cheryl Nickerson and her team at the Biodesign Institute at Arizona State University highlight an innovative approach for studying cells in 3-D. They are examining the potential of such research to greatly expand science's understanding of disease onset and progression, particularly the responses of host cells to infectious pathogens. Such work provides fresh insight into the mechanisms of infectious disease and holds the potential for the design of novel or improved therapeutics, more accurate drug screening and improved evaluation of potential vaccine candidates.

Despite enormous progress in understanding how infectious pathogens successfully evade the immune system and cause disease, and the successful treatment or eradication of some of these deadly illnesses; infectious diseases remain a huge health and economic burden, particularly in the developing world. They continue to cause roughly 35 percent of all fatalities worldwide, killing some 14-17 million people annually. Many of these deaths could be prevented through the development of in vitro models of human cells and tissues that better mimic in vivo environments.

Before the advent of 3-D culturing methods, human cells used for research were typically grown on flat surfaces (often composed of treated polystyrene or glass), resulting in the growth of 2-D cell sheets known as monolayers. However, isolating cells from their 3-D architecture and native microenvironment comes at a price. As Jennifer Barrila, one of the lead authors of this review explains, "we know that if you take a biopsy from a tissue, homogenize it and plate it on a flat surface and follow its growth, it's going to immediately de-differentiate and start losing a lot of the features and functions that it normally has in the body, because it is no longer in that characteristic 3-D shape. "
 
 

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