Mice Regrow Fingertips, Hair With Help of Mitochondria-Boosting Protein
November 11, 2013 5:05 PM
Research could lead to a topical treatment for burns or baldness in humans
Boston Children's Hospital
Stem Cell Program
(HMS) have made an exciting discovery, discovering two ways by which a special gene family found in mice and humans alike can trigger tissue regeneration.
The study shows that the key repair protein produced from this gene family can not only inhibit aging/maturation proteins that slow down healing, but also directly kick-start mitochondria, a cell's power plants. This second mechanism helps to produce the energy required for vigorous healing. And even better, the study shows that small molecules can mimic this protein activity, raising the hope of developing sprays or creams that stimulate healing via boosting cellular metabolism, with potential for treating limb injuries in young children, fighting baldness in adults, and even treating severe burns.
I. Meet LIN28 -- a Super-Gene
The secret lies in the family of genes
, which were first discovered in earthworms.
-family genes have since been found in all "advanced" organism, including mice and humans, which express homologue A of the gene (which is hence dubbed
Researchers began to suspect
genes played a role in tissue growth and/or regeneration, after noticing they were
[abstract] in embryonic stem cells from humans and other organisms. Much of the research to date on
has focused on using it to
"trick" cells from mature tissues
living skin cells
into becoming stem cells, that offer similar healing potential to traditional stem cells from embryonic stem cells, albeith with a higher cancer risk. This approach may produce less carcinogenic resulting stem cells, versus
approaches that uses other genes, including
A new study shows just why
homologue A (
) is so crucial for promoting regenerative capabilities in stem cells -- it both promotes expression of other regenerative factors like
, and boost mitochondrial metabolism to produce energy for healing. [Image Source: EMW/Wikimedia Commons]
[abstract] from the
Univ. of Wisconsin-Madison
reported that by swamping --
-- so called "oncogenes", whose overexpression can cause cancer -- for
, can not only improve conversion efficiency in induced pluripotent stem-cells, but also may result in a less tumorigenic line.
Now this new research demonstrates that even outside of inducing pluripotency, there may be therapeutic potential for tricking cells into producing
. The researchers damaged various tissues in mice then induced
expression. Some, but not all tissues showed a remarkable regenerative capability.
For example, "finger" tips that were clipped in newborn mice, grew to a healthy state.
was also shown to heal broken/damaged cartilage and bones, to regrow hair, and heal soft tissues (such as skin and subcutaneous fat layers).
The middle and index fingertips did not regrow in an untreated mouse (top), but in a baby mouse treated with LIN28 induction therapy, they regrew like they were never injured. [Image Source: HMS/Cell]
expression in skin tissue on the back of mice, the researchers were able to trigger hair regrowth, even in cases where follicles were removed via waxing. This raises hope that
could be used in humans as a cure for baldness.
The work also shows potential for treating serious limb or digit injuries in children, which may show similar gains if the injury occurs and is treated while the child is very young.
II. Cells Need Lots of Energy to Heal -- and
The new work was performed by the Harvard Medical School's
, which is led by Dr. George Q. Daley. Singapore native
, a Harvard Medical School Ph.D. candidate coauthored the work with a post-doc, Dr. Hao Zhu.
Mr. Shyh-Chang explains the recent experiments
Most people would naturally think that growth factors are the major players in wound healing, but we found that the core metabolism of cells is rate-limiting in terms of tissue repair. The enhanced metabolic rate we saw when we reactivated LIN28A is typical of embryos during their rapid growth phase.
LIN28A could be a key factor in constituting a healing cocktail, but there are other embryonic factors that remain to be found.
The researchers already knew that
's actions were in part driven by it attaching to RNA and enhancing the rate of transcription for certain proteins that stimulated growth and healing. They focused their initial investigation on
, which is known to promote cell maturation and aging. Inhibiting
expression and/or action was shown to be a key mechanism of
rejuvenatory action in past studies, such as
this 2011 work
Dr. Richard Gregory
's group (another Harvard Medical School group studying stem cells).
translation. [Image Source: HMS/Cell]
But the researchers found that the
proteins also were localized in the cell's mitochondria, a place where little LET-7 was found. This suggested that an additional effect might be at play. Upon closer investigation the researchers were able to show that the protein also boosted the expression of certain mitochondrial genes, bumping the cell's metabolism in order to crank up its biochemical power levels in preparation for healing.
Mr. Shyh-Change explains:
We were confident that LET-7 would be the mechanism, but there was something else involved. We already know that accumulated defects in mitochondrial metabolism can lead to aging in many cells and tissues. We are showing the converse -- that enhancement of mitochondrial metabolism can boost tissue repair and regeneration, recapturing the remarkable repair capacity of juvenile animals.
The study was not without its disappointments. Getting even tisssues in mice to express the key
gene was admittedly difficult. And even when they could get sufficient expression levels, some adult tissues -- e.g. heart tissue and adult "finger" tips -- showed no regeneration.
was shown to act not just via
inhibitory interactions (left), but also by boosting mitochondrial metabolism. [Image Source: Cell/HMS]
However, the researchers also offered a potential roadmap to short term therapeutic approaches by using small synthetic biomolecules to mimic the action of
on mitochondrial DNA and trick tissues to increase their metabolism, enhancing healing rate. Even without
present, this approach was able to offer many of the same benefits.
Mr. Shyh-Chang concludes:
Since LIN28 itself is difficult to introduce into cells, the fact that we were able to activate mitochondrial metabolism pharmacologically gives us hope.
Grad student Shyh-Chang Ng (left); Harvard professors Drs. George Daley (bottom middle) and Richard Gregory (far right), along with grad student Srinivas Viswanathan (top, right) [Image Source: HMS]
Dr. Daley, the lab leader and senior author of the study on the work adds:
Efforts to improve wound healing and tissue repair have mostly failed, but altering metabolism provides a new strategy which we hope will prove successful.
The paper was
in the prestigious peer-reviewed journal
. The team plans to next examine other critical genes that grant stem cells their marvelous regenerative abilities and to investigate whether the small-molecule metabolism booster could be applicable to boosting wound healing in human soft tissues.
Eurekalert [press release]
"We basically took a look at this situation and said, this is bullshit." -- Newegg Chief Legal Officer Lee Cheng's take on patent troll Soverain
Researchers Make Leap in Stem Cell Research; Cells Can Now be Produced From Any Tissue
July 2, 2008, 10:03 AM
Artificially Created Stem Cells Cure Sickle Cell in Mice
December 8, 2007, 7:25 PM
Amidst Stem Cell Veto, New Research Blazes Trails
June 14, 2007, 3:48 AM
Cyber Hackers Threaten Security of Lifesaving Medical Devices
October 19, 2016, 8:09 AM
Innovative Neurotechnology in Sound Therapy Reduces High Blood Pressure and Migraines
October 16, 2016, 5:00 AM
Researchers Move Closer to Breakthrough Gene Therapy to Cure Sickle Cell
October 14, 2016, 5:00 AM
Keytruda: A breakthrough treatment to increase survival rates for lung cancer patients
October 12, 2016, 5:00 AM
CDC Warning about Record High Increases in 2016 for Polio-like Illness causing Paralysis
October 9, 2016, 5:00 AM
Hypertension in children impacts cognitive performance
October 5, 2016, 5:00 AM
Most Popular Articles
Problems with Windows 10 – Update Now
October 15, 2016, 7:30 AM
End of the Road for the Audi R8 e-tron
October 15, 2016, 5:00 AM
Is Razer Blade Stealth Laptop For You?
October 16, 2016, 5:00 AM
Bluetooth Saves Lives
October 16, 2016, 7:05 AM
IBM – Cloud Object Storage Cheaper than Amazon S3
October 14, 2016, 5:00 AM
Latest Blog Posts
Nasa Flies Drones at Nevada Airport
Oct 21, 2016, 8:21 AM
T-Mobile Data Problems
Oct 20, 2016, 10:17 AM
Annoying Apple Watch Problems and How to Fix Them
Oct 20, 2016, 5:00 AM
Your Mail May Soon Be Delivered By Robot
Oct 19, 2016, 9:34 AM
2018 Jeep Wrangler Prototype Sells At Junkyard
Oct 18, 2016, 5:00 AM
Samsung Shines with Gold Edition Tablet
Oct 17, 2016, 9:24 AM
Tesla Hints Mysterious Product Debut for October 17th
Oct 16, 2016, 10:14 AM
Samsung Galaxy Note 7 Phones on US flights
Oct 15, 2016, 5:00 AM
Comcast Fined $2.3 Million For Unconfirmed Services Charged To Customers
Oct 14, 2016, 5:00 AM
“American singer / songwriter “Bob Dylan is awarded 2016 Nobel Prize in Literature.
Oct 13, 2016, 10:33 AM
Battery Defect in Medical Device
Oct 12, 2016, 5:00 AM
IBM Bolsters Social Services Sector With Technology Grants
Oct 11, 2016, 5:00 AM
Scientists Sound Alarm on Climate but US Still Toys With Skepticism
Oct 10, 2016, 5:00 AM
IMEX America Trade Show
Oct 9, 2016, 10:00 AM
Phone Wars – Google VS Samsung Free Gifts on Purchase
Oct 6, 2016, 5:00 AM
Member of Parliament’s opposition car exploded in Tbilist capital of Georgia
Oct 5, 2016, 2:52 PM
US Government Cuts Cord On Internet Oversight
Oct 3, 2016, 10:34 AM
Are farm children less likely to have allergies and asthma in adulthood?
Sep 30, 2016, 5:00 AM
More Blog Posts
Copyright 2016 DailyTech LLC. -
Terms, Conditions & Privacy Information