We have massive wounds in our brains. What research is needed to see what migration patterns of cells are needed in the brain to advance our recovery? This is going to be incredibly difficult, so which stroke leader is going to step up and tackle this? Or is everyone too chickenshit and just waiting around for somebody else to solve the problem?
http://www.rdmag.com/news/2015/03/unlocking-mysteries-wound-healing?
Researchers at the Univ. of Arizona have discovered what causes and
regulates collective cell migration, one of the most universal but least
understood biological processes in all living organisms.
The findings, published in Nature Communications, shed light
on the mechanisms of cell migration, particularly in the wound healing
process. The results represent a major advancement for regenerative
medicine, in which biomedical engineers and other researchers manipulate
cells' form and function to create new tissues, and even organs, to
repair, restore or replace those damaged by injury or disease.
"The results significantly increase our understanding of how tissue
regeneration is regulated and advance our ability to guide these
processes," said Pak Kin Wong, UA associate professor of mechanical and
aerospace engineering and lead author of the article.
"In recent years, researchers have gained a better understanding of
the molecular machinery of cell migration, but not what directs it to
happen in the first place," he said. "What, exactly, is orchestrating
this system common to all living organisms?"
Leaders of the pack
The answer, it turns out, involves delicate interactions between
biomechanical stress, or force, which living cells exert on one another,
and biochemical signaling.
The UA researchers discovered that when mechanical force
disappears—for example at a wound site where cells have been destroyed,
leaving empty, cell-free space—a protein molecule, known as DII4,
coordinates nearby cells to migrate to a wound site and collectively
cover it with new tissue. What's more, they found, this process causes
identical cells to specialize into leader and follower cells.
Researchers had previously assumed leader cells formed randomly.
Wong's team observed that when cells collectively migrate toward a
wound, leader cells expressing a form of messenger RNA, or mRNA, genetic
code specific to the DII4 protein emerge at the front of the pack, or
migrating tip. The leader cells, in turn, send signals to follower
cells, which do not express the genetic messenger. This elaborate
autoregulatory system remains activated until new tissue has covered a
wound.
The same migration processes for wound healing and tissue development
also apply to cancer spreading, the researchers noted. The combination
of mechanical force and genetic signaling stimulates cancer cells to
collectively migrate and invade healthy tissue.
Biologists have known of the existence of leader cells and the DII4
protein for some years and have suspected they might be important in
collective cell migration. But precisely how leader cells formed, what
controlled their behavior, and their genetic makeup were all
mysteries—until now.
Broad medical applications
"Knowing the genetic makeup of leader cells and understanding their
formation and behavior gives us the ability to alter cell migration,"
Wong said.
With this new knowledge, researchers can re-create, at the cellular
and molecular levels, the chain of events that brings about the
formation of human tissue. Bioengineers now have the information they
need to direct normal cells to heal damaged tissue, or prevent cancer
cells from invading healthy tissue.
The UA team's findings have major implications for people with a
variety of diseases and conditions. For example, the discoveries may
lead to better treatments for non-healing diabetic wounds, the No. 1
cause of lower limb amputations in the U.S.; for plaque buildup in
arteries, a major cause of heart disease; and for slowing or even
stopping the spread of cancer, which is what makes it so deadly.
The research also has the potential to speed up development of
bioengineered tissues and organs that can be successfully transplanted
in humans.
About the study
In the UA Systematic Bioengineering Laboratory, which Wong directs,
researchers used a combination of single-cell gene expression analysis,
computational modeling and time-lapse microscopy to track leader cell
formation and behavior in vitro in human breast cancer cells and in vivo
in mice epithelial cells under a confocal microscope.
Their work included manipulating leader cells through pharmacological, laser and other means to see how they would react.
"Amazingly, when we directed a laser at individual leader cells and
destroyed them, new ones quickly emerged at the migrating tip to take
their place," said Wong, who likened the mysteries of cell migration and
leader cell formation to the processes in nature that cause geese to
fly in V-formation or ants to build a colony.
Source: Univ. of Arizona
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