Spiny mice regenerate damaged kidneys without scarring

Date:
November 3, 2021
Source:
Cell Press
Summary:
Spiny mice are known for their ability to heal severe skin wounds
without so much as a scar. Now, researchers have discovered that
they also can regenerate severely damaged internal organs that, in
other mice, would lead to fatal organ failure. The findings in spiny
mice are the first to show kidney regeneration in an adult mammal.



FULL STORY ========================================================================== Spiny mice are known for their ability to heal severe skin wounds
without so much as a scar. Now, researchers reporting in the journal
iScience on November 3, have discovered that they also can regenerate
severely damaged internal organs that, in other mice, would lead to
fatal organ failure. The findings in spiny mice are the first to show
kidney regeneration in an adult mammal.


==========================================================================
"The global health burden for loss of vital organ function due to
progressive tissue fibrosis is enormous," says Mark Majesky, a principal investigator at Seattle Children's Research Institute and professor of pediatrics at the University of Washington. "Very few treatment options
are currently available for patients with end-stage kidney disease or
similar degenerative fibrotic diseases of the heart, lungs, liver, or reproductive organs. Our group took a different approach to this problem
and looked to nature to provide clues that might lead to novel therapies." Earlier studies of wound healing in spiny mice (genus Acomys) suggested to Majesky and colleagues (including Daryl Okamura, an attending physician
and associate professor of pediatrics at the University of Washington)
showed that the animals had -- over the course of their evolution --
solved the problem of tissue fibrosis (scarring) after injury. But
could they also heal damaged internal organs the same way? To find out,
they exposed spiny mice to conditions that are known to cause serious
kidney injury in other mice (genus Mus). Their studies showed that,
although spiny mice suffered the same degree of tissue injury initially,
they were nevertheless able to completely heal: they regenerated an
apparently healthy kidney with no signs of fibrosis. As expected, other
mice treated in the same way progressed to organ failure.

"The dramatic and complete recovery of kidney function over a two-week
time course in spiny mice was quite surprising to us," Okamura says. "The
types of severe injuries we used were chosen because they produce a
decisive and rapid loss of kidney function in mice and led to complete
organ failure over the same two-week period." To find out how the spiny
mice do it, the researchers took a comprehensive look at the genes they express. Their studies suggest that the spiny mouse genome is poised at
the time of injury to launch a rapid, scarless regenerative response
in surviving kidney cells. The analysis uncovered differences between
Acomys and Mus in the activity of 843 genes in six unique clusters.

They also saw a delayed response by immune cells called macrophages,
which are known to play a role in fibrosis. Unlike in other mice,
macrophages didn't appear on the scene for about a week.

"We have opened a new window on the development of possible therapies
for chronic kidney disease, that may perhaps apply to other organs that similarly exhibit loss of function due to progressive tissue fibrosis,"
Majesky says.

"Our goal is to learn what nature has done in evolving a mammalian genome
that heals tissue injury by regeneration without fibrotic scarring and
apply the lessons learned to the development of new therapies for kidney disease," Okamura adds.

========================================================================== Story Source: Materials provided by Cell_Press. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Daryl M. Okamura, Chris M. Brewer, Paul Wakenight, Nadia Bahrami,
Kristina Bernardi, Amy Tran, Jill Olson, Xiaogang Shi, Szu-Ying Yeh,
Adrian Piliponsky, Sarah J. Collins, Elizabeth D. Nguyen, Andrew E.

Timms, James W. MacDonald, Theo K. Bammler, Branden R. Nelson,
Kathleen J. Millen, David R. Beier, Mark W. Majesky. Spiny mice
activate unique transcriptional programs after severe kidney
injury regenerating organ function without fibrosis. iScience,
2021; 103269 DOI: 10.1016/ j.isci.2021.103269 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211103115451.htm

--- up 8 weeks, 6 days, 8 hours, 25 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)