Posts tagged tissue regeneration
Articles and news from the latest research reports.
Opposites attract: How cells and cell fragments move in electric fields
Like tiny, crawling compass needles, whole living cells and cell fragments orient and move in response to electric fields — but in opposite directions, scientists at the University of California, Davis, have found. Their results, published April 8 in the journal Current Biology, could ultimately lead to new ways to heal wounds and deliver stem cell therapies.
When cells crawl into wounded flesh to heal it, they follow an electric field. In healthy tissue there’s a flux of charged particles between layers. Damage to tissue sets up a “short circuit,” changing the flux direction and creating an electrical field that leads cells into the wound. But exactly how and why does this happen? That’s unclear.
"We know that cells can respond to a weak electrical field, but we don’t know how they sense it," said Min Zhao, professor of dermatology and ophthalmology and a researcher at UC Davis’ stem cell center, the Institute for Regenerative Cures. "If we can understand the process better, we can make wound healing and tissue regeneration more effective.”
The researchers worked with cells that form fish scales, called keratocytes. These fish cells are commonly used to study cell motion, and they also readily shed cell fragments, wrapped in a cell membrane but lacking a nucleus, major organelles, DNA or much else in the way of other structures.
In a surprise discovery, whole cells and cell fragments moved in opposite directions in the same electric field, said Alex Mogilner, professor of mathematics and of neurobiology, physiology and behavior at UC Davis and co-senior author of the paper.
It’s the first time that such basic cell fragments have been shown to orient and move in an electric field, Mogilner said. That allowed the researchers to discover that the cells and cell fragments are oriented by a “tug of war” between two competing processes.
Think of a cell as a blob of fluid and protein gel wrapped in a membrane. Cells crawl along surfaces by sliding and ratcheting protein fibers inside the cell past each other, advancing the leading edge of the cell while withdrawing the trailing edge.
Assistant project scientist Yaohui Sun found that when whole cells were exposed to an electric field, actin protein fibers collected and grew on the side of the cell facing the negative electrode (cathode), while a mix of contracting actin and myosin fibers formed toward the positive electrode (anode). Both actin alone, and actin with myosin, can create motors that drive the cell forward.
The polarizing effect set up a tug-of-war between the two mechanisms. In whole cells, the actin mechanism won, and the cell crawled toward the cathode. But in cell fragments, the actin/myosin motor came out on top, got the rear of the cell oriented toward the cathode, and the cell fragment crawled in the opposite direction.
The results show that there are at least two distinct pathways through which cells respond to electric fields, Mogilner said. At least one of the pathways — leading to organized actin/myosin fibers — can work without a cell nucleus or any of the other organelles found in cells, beyond the cell membrane and proteins that make up the cytoskeleton.
Upstream of those two pathways is some kind of sensor that detects the electric field. In a separate paper to be published in the same journal issue, Mogilner and Stanford University researchers Greg Allen and Julie Theriot narrow down the possible mechanisms. The most likely explanation, they conclude, is that the electric field causes certain electrically charged proteins in the cell membrane to concentrate at the membrane edge, triggering a response.
Biocompatible sponge can be injected to deliver stem cells and drugs into the body
Biocompatible scaffolds, like those developed to stimulate the repair of heart tissue and bone and cartilage in the body, would normally need to be implanted surgically. Now bioengineers at Harvard University have developed a compressible bioscaffold that can be delivered via a syringe before popping back to its original shape inside the body. The material is also able to be loaded up with drugs or living cells that are gradually released as the material breaks down.
The injectable sponge is made up primarily of a seaweed-based jelly called alginate. It is actually a sponge-like gel that is formed through a freezing process called cryogelation. When the water in the alginate solution starts to freeze, pure ice crystals are formed and the surrounding gel becomes more concentrated as it sets. Later, the ice crystal melt to leave a network of large pores that allow liquids and large molecules to easily flow through it. Live cells can be attached to the walls of this network and large and small proteins and drugs can also be held within the alginate jelly itself.
Unlike other alginate gels that are brittle, using this method the researchers were able to produce a strong, compressible gel by carefully calibrating the alginate mixture and the timing of the freezing process.
The research team led by principal investigator David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS), demonstrated that cells and drugs can be delivered into the body intact along with the sponge through a small bore needle. Once inside the body, the sponge returns to its original shape and gradually releases its cargo as it breaks down.
“What we’ve created is a three-dimensional structure that you could use to influence the cells in the tissue surrounding it and perhaps promote tissue formation,” explains Mooney. “The simplest application is when you want bulking. If you want to introduce some material into the body to replace tissue that’s been lost or that is deficient, this would be ideal. In other situations, you could use it to transplant stem cells if you’re trying to promote tissue regeneration, or you might want to transplant immune cells, if you’re looking at immunotherapy.”
'Scar free healing' in mice may give clues to human skin repair
Mice with brittle skin, which tears off in order to escape predators, may offer clues to healing wounds without scarring, according to US researchers.
Some African spiny mice lost up to 60% of the skin from their backs, says the study published in the journal Nature. Unlike wounds in other mammals, the skin then rapidly healed and regrew hairs rather than forming a scar. Scientists want to figure out how the healing takes place and if it could apply to people.
Salamanders, some of which can regrow entire limbs, are famed for their regenerative abilities. It has made them the focus of many researchers hoping to figure out how to produce the same effect in people. Mammals, however, have very limited ability to regrow lost organs. Normally a scar forms to seal the wound. “This study shows that mammals as a group may in fact have higher regenerative abilities then they are given credit for,” said Dr Ashley Seifert from the University of Florida.
(Source: BBC)
Understanding how salamanders grow new limbs provides insights into the potential of human regenerative medicine
By studying a real lizard-like amphibian, which can regenerate missing limbs, the Salk researchers discovered that it isn’t enough to activate genes that kick start the regenerative process. In fact, one of the first steps is to halt the activity of so-called jumping genes.
In research published August 23 in Development, Growth & Differentiation, and July 27 in Developmental Biology, the researchers show that in the Mexican axolotl, jumping genes have to be shackled or they might move around in the genomes of cells in the tissue destined to become a new limb, and disrupt the process of regeneration.
They found that two proteins, piwi-like 1 (PL1) and piwi-like 2 (PL2), perform the job of quieting down jumping genes in this immature tadpole-like form of a salamander, known as an axolotl - a creature whose name means water monster and who can regenerate everything from parts of its brain to eyes, spinal cord, and tail.
"What our work suggests is that jumping genes would be an issue in any situation where you wanted to turn on regeneration," says the studies’ senior author, Tony Hunter, a professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center.