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The quest for cell culture under more normal physiologic conditions takes an interesting “twist” in this week’s patent of the week. Describing previous traditional two and three-dimensional cell culture techniques as “static,” these inventors from Japan have constructed a “bendable” medium in which cells can be repeatedly flexed to create compressive and tensile forces on the cells.
The inventors point out that many (if not most or all) regions of the human body are subject to near-continuous dynamic stresses. For example, vertebral discs, menisci, bones, cartilage and heart valve receive considerable bending stress in vivo. Yet traditional cell culture techniques, even three-dimensional techniques, do not replicate these stresses. The authors believe that these stresses, or as they more simply put it, “bending,” are critical to normal growth and function.
One device to accomplish this bending is elegantly simple, as can be seen from the conceptual drawings above, taken from the patent. Cells are cultured in flexible tubes (32), which extend lengthwise on a flexible bed from what is essentially a fulcrum point (28). When downward pressure (40) is applied to the fulcrum point of the bed, as seen in the lower drawing, the bed flexes and cells undergo bending force. Conversely, pressure could be applied upwards at the fulcrum point, in which case the formerly compressive force would instead be tensile. From a mathematical model, the alternating compression and extension is thought to create alternating waves of increasing and decreasing intracellular pressure.
Does it matter from a functional viewpoint? It seems a little early to tell. In a single reported experiment, sections of mouse vertebra were cultured “statically,” as they describe traditional culture, and in a second culture with repeated bending motion, for ten days. Photomicrographs appear to show an increase in cell density and an increase in cellular matrices.
A lot more work will obviously be necessary to prove this out. However, before dismissing the idea, remember that we once thought that exposing cells to hyperoxic conditions didn’t matter either. One more step in rethinking the many possible differences between cultured, and in vivo cells.
U.S. Pat. No. 8,431,544
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