Scientists regrow frog's lost leg
Frogs briefly treated with a five-drug cocktail administered by a
wearable bioreactor on the stump were able to regrow a functional, nearly complete limb
Date:
January 26, 2022
Source:
Tufts University
Summary:
Scientists have triggered long-term growth of legs in adult frogs,
which are naturally unable to regenerate limbs. The frogs regrew
a lost leg over months, triggered by just 24 hour exposure to
a five-drug cocktail held under a bioreactor. The new legs were
functional enough to enable sensation and locomotion.
FULL STORY ==========================================================================
For millions of patients who have lost limbs for reasons ranging from
diabetes to trauma, the possibility of regaining function through natural regeneration remains out of reach. Regrowth of legs and arms remains
the province of salamanders and superheroes.
==========================================================================
But in a study published in the journal Science Advances, scientists at
Tufts University and Harvard University's Wyss Institute have brought
us a step closer to the goal of regenerative medicine.
On adult frogs, which are naturally unable to regenerate limbs, the
researchers were able to trigger regrowth of a lost leg using a five-drug cocktail applied in a silicone wearable bioreactor dome that seals in
the elixir over the stump for just 24 hours. That brief treatment sets
in motion an 18-month period of regrowth that restores a functional leg.
Many creatures have the capability of full regeneration of at least some
limbs, including salamanders, starfish, crabs, and lizards. Flatworms
can even be cut up into pieces, with each piece reconstructing an entire organism. Humans are capable of closing wounds with new tissue growth,
and our livers have a remarkable, almost flatworm-like capability of regenerating to full size after a 50% loss.
But loss of a large and structurally complex limb -- an arm or leg --
cannot be restored by any natural process of regeneration in humans or
mammals. In fact, we tend to cover major injuries with an amorphous mass
of scar tissue, protecting it from further blood loss and infection and preventing further growth.
Kickstarting Regeneration The Tufts researchers triggered the regenerative process in African clawed frogs by enclosing the wound in a silicone
cap, which they call a BioDome, containing a silk protein gel loaded
with the five-drug cocktail.
==========================================================================
Each drug fulfilled a different purpose, including tamping down
inflammation, inhibiting the production of collagen which would lead
to scarring, and encouraging the new growth of nerve fibers, blood
vessels, and muscle. The combination and the bioreactor provided a local environment and signals that tipped the scales away from the natural
tendency to close off the stump, and toward the regenerative process.
The researchers observed dramatic growth of tissue in many of the treated frogs, re-creating an almost fully functional leg. The new limbs had
bone structure extended with features similar to a natural limb's bone structure, a richer complement of internal tissues (including neurons),
and several "toes" grew from the end of the limb, although without the
support of underlying bone.
The regrown limb moved and responded to stimuli such as a touch from
a stiff fiber, and the frogs were able to make use of it for swimming
through water, moving much like a normal frog would.
"It's exciting to see that the drugs we selected were helping to create
an almost complete limb," said Nirosha Murugan, research affiliate at the
Allen Discovery Center at Tufts and first author of the paper. "The fact
that it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests that frogs and perhaps other
animals may have dormant regenerative capabilities that can be triggered
into action." The researchers explored the mechanisms by which the brief intervention could lead to long-term growth. Within the first few days
after treatment, they detected the activation of known molecular pathways
that are normally used in a developing embryo to help the body take shape.
========================================================================== Activation of these pathways could allow the burden of growth and
organization of tissue to be handled by the limb itself, similar to
how it occurs in an embryo, rather than require ongoing therapeutic intervention over the many months it takes to grow the limb.
How the BioDome Works Animals naturally capable of regeneration live
mostly in an aquatic environment. The first stage of growth after loss of
a limb is the formation of a mass of stem cells at the end of the stump
called a blastema, which is used to gradually reconstruct the lost body
part. The wound is rapidly covered by skin cells within the first 24
hours after the injury, protecting the reconstructing tissue underneath.
"Mammals and other regenerating animals will usually have their injuries exposed to air or making contact with the ground, and they can take days
to weeks to close up with scar tissue," said David Kaplan, Stern Family Professor of Engineering at Tufts and co-author of the study. "Using
the BioDome cap in the first 24 hours helps mimic an amniotic-like
environment which, along with the right drugs, allows the rebuilding
process to proceed without the interference of scar tissue." Next Steps
in Frogs and Mammals Previous work by the Tufts team showed a significant degree of limb growth triggered by a single drug, progesterone, with the BioDome. However, the resulting limb grew as a spike and was far from
the more normally shaped, functional limb achieved in the current study.
The five-drug cocktail represents a significant milestone toward
the restoration of fully functional frog limbs and suggests further
exploration of drug and growth factor combinations could lead to regrown
limbs that are even more functionally complete, with normal digits,
webbing, and more detailed skeletal and muscular features.
"We'll be testing how this treatment could apply to mammals next," said corresponding author Michael Levin, Vannevar Bush Professor of Biology
in the School of Arts & Sciences, director of the Allen Discovery Center
at Tufts, and associate faculty member of the Wyss Institute.
"Covering the open wound with a liquid environment under the BioDome,
with the right drug cocktail, could provide the necessary first
signals to set the regenerative process in motion," he said. "It's
a strategy focused on triggering dormant, inherent anatomical
patterning programs, not micromanaging complex growth, since adult
animals still have the information needed to make their body structures." ========================================================================== Story Source: Materials provided by Tufts_University. Original written
by Mike Silver. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Nirosha J. Murugan, Hannah J. Vigran, Kelsie A. Miller, Annie
Golding,
Quang L. Pham, Megan M. Sperry, Cody Rasmussen-Ivey, Anna W. Kane,
David L. Kaplan, Michael Levin. Acute multidrug delivery via a
wearable bioreactor facilitates long-term limb regeneration and
functional recovery in adult Xenopus laevis. Science Advances,
2022; 8 (4) DOI: 10.1126/sciadv.abj2164 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/01/220126144001.htm
--- up 7 weeks, 4 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)