Source: Harvard Creates Cyborg Tissues
On the left: A mouse embryo preserved in para-formaldehyde. On the right: A mouse embryo soaked in Scale for two weeks.
What’s the News: The trouble with brains, organs, and tissues in general, from a biologist’s perspective, is that they scatter light like nobody’s business. Shine a light into there to start snapping pictures of cells with your microscope, and bam, all those proteins and macromolecules bounce it around and turn everything to static before you’ve gotten more than a millimeter below the surface. Scientists at RIKEN in Japan, however, have just published a special recipe for a substance that makes tissue as transparent as Jell-O, making unprecedentedly deep imaging possible.
How the Heck:
- Substances to make tissue more transparent are called clearing agents, and the ones we have now have varying degrees of penetration—in other words, they don’t always take you as deep as you’d like. To boot, they sometimes mess with the fluorescent tags that biologists splice into certain tissues to light up a particular set of blood vessels or neurons, for example.
- This recipe clears out tissue so well that the only limitation on how deep you can see is the power of the lens of the microscope. And, as the researchers proved when they used it to image part of a mouse brain, it doesn’t diminish the glow of the fluorescent tags they’d engineered the mouse to express.
- The clearing agent is called Scale, and, serendipitously, it’s made from odds and ends that any lab will have lying around. Urea, which most of us know as a compound in urine; Triton-X, a detergent biologists use to make cell membranes more permeable; and glycerol, which is used in antifreeze, are all it takes to whip up a batch.
- Once the team figured out the correct proportions of each, they soaked mouse brains, mouse brain slices, and the above embryos in the stuff for two weeks and examined the results under the microscope. They were able to see at least several millimeters below the surface and, by activating fluorescent labels in neurons with a laser light, traced patterns neurons in the hippocampus and other areas of the brain.
A mouse brain soaked in Scale looks like tiny glob of jello. Turn
off the lights and shine a laser through it, and the light shoots
What’s the Context:
- The researchers suggest that the clearing agent could be useful for drawing connectivity maps of the brain, a field known as connectomics.
- Tracing circuits in the brain is such delicate work that it is still done by hand, and some of the most exciting new imaging methods focus on making clearer and deeper pictures of neurons for use in such cartography.
- Scale is unusual among these, however, because instead of using algorithms to cancel out fuzz in the image or bypassing light entirely by using certain types of fMRI, it alters the tissue itself to be more amendable to viewing.
The Future Holds: Though this time the team used it to study the brain, Scale can be used in any tissue. The downside is that, like other clearing agents and treatments, Scale only works with dead tissue, so don’t expect to see barrel-fish-like mice wandering around in labs just yet. But the team is working on a milder version that they hope could be used in living creatures in the future.
Reference: Hama, et al. Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience (30 August 2011). doi:10.1038/nn.2928
Image courtesy of Nature Neuroscience and Hama, et al.
Before LED light is shined on it, the injected gel is still fluid and
can fill up any gaps of spaces under the skin.
What’s the News: Scientists have developed a gel that could be used to rebuild the faces of crash victims. Activated by light, it solves several of the problems inherent in the usual methods.
What’s the Context:
- Dealing with damaged soft tissue is often more complex than dealing with damaged bone and skin. The shape of someone’s face is dependent on the fat, muscle, and other tissue below the surface, and doctors trying to restore someone’s facial structure must contend with scar tissue, swelling, and loss of movement.
- Current methods include injecting hyaluronic acid (HA), a naturally occurring molecule that helps thicken the gel that surrounds cells in the body, or synthetic materials, but both of these have their issues: HA injections don’t last, and synthetic materials can cause inflammation. Grafting soft tissue from other parts of the body is also an option, but that can cause scar tissue to form where it was removed and at the graft site.
- Additionally, it’s not possible to control the shape of the synthetic materials after they’re put in the body, nor can the HA be made to conform to a certain shape.
How the Heck:
- The new substance is made of HA mixed with an FDA-approved plastic, polyethylene glycol, or PEG. Experimenting in rats, the researchers found that just the right mixture of the two alleviates the problems experienced by solely synthetic or solely biological implants or grafts. More than a year after the rats received the implants, they had maintained their shape.
- Importantly, the material can be molded and set once it’s inside the body. First, it’s injected into the desired area, then massaged into the right shape. When it’s in the right configuration, shining an LED light over the skin causes the molecules to crosslink and firm up.
- The team also tried the substance on several human volunteers who were having tummy tucks and found that it held up well for 12 weeks after surgery.
The Future Holds: Future research will investigate more specifically how the gel will work in humans—the researchers noticed more inflammation than they expected in their volunteers, so sussing out how it interacts with the human immune system is next on the agenda.
Reference: Hillel et al. Photoactivated Composite Biomaterial for Soft Tissue Restoration in Rodents and in Humans. Sci Transl Med 27 July 2011: Vol. 3, Issue 93, p. 93ra67 DOI: 10.1126/scitranslmed.3002331
Image credit: Hillel et al. Science Trans Med
An anonymous reader writes “Men with type 1 diabetes may be able to grow their own insulin-producing cells from their testicular tissue, say Georgetown University Medical Center (GUMC) researchers who presented their findings today at the American Society of Cell Biology 50th annual meeting in Philadelphia. Their laboratory and animal study is a proof of principle that human spermatogonial stem cells (SSCs) extracted from testicular tissue can morph into insulin-secreting beta islet cells normally found in the pancreas. And the researchers say they accomplished this feat without use of any of the extra genes now employed in most labs to turn adult stem cells into a tissue of choice.”