How do animals regrow their limbs? And why can't humans do it? - Jessica Whited
For some animals, losing a limb
is a decidedly permanent affair.
But for salamanders,
particularly axolotls,
amputation is just a temporary affliction.
Not only can they grow back entire limbs
in as little as six weeks,
they can also regenerate heart
and even brain tissue.
So how does this astonishing
adaptation work?
Regardless of regeneration,
every limbed creature had to grow
their arms and legs at some point.
And whether that process starts
in the womb or the world,
it almost always begins
with little bumps called limb buds.
These buds are full of progenitor cells—
a cornucopia of cell types that can
differentiate into various tissues,
including muscles, cartilage, ligaments,
and tendons.
Some of these progenitors are stem cells,
capable of developing into a range
of specialized cells and tissues,
while others are merely derived
from stem cells.
But in either case, the progenitors
differentiate and multiply rapidly
as the limb bud develops.
Nerves grow into the limb
from nearby cell bodies
and a network of blood vessels form
which fuel the process with oxygen.
Eventually, that tiny bud grows
into a full infant limb.
Most salamanders, including axolotls,
develop their limbs in the same way.
But unlike other animals, they can also
start this process all over again
if they need to.
When salamanders lose a limb,
surrounding skin cells
quickly surge across the wound’s surface.
This new layer of skin is called
the wound epidermis,
and once established, it signals cells
in the underlying limb stump
to undergo something
called dedifferentiation.
This process reverts nearby cells
from fully developed limb tissues
back into earlier, less specialized
progenitor cells.
At the same time, the peripheral nervous
system fires up stem cells
throughout the salamander’s body.
This would be impossible
for most multicellular organisms,
whose stem cells typically lose their
regenerative capacity with age.
But when salamander stem cells
near the injury get the right signal,
they reactivate and start multiplying.
Researchers don’t know what ratio
of stem cells
and dedifferentiated progenitor cells
regeneration requires.
But we do know these cells come together
to form the most important part
of the process: the blastema.
This structure is almost identical
to a limb bud—
the primary difference is that it’s
made of recycled, repurposed cells,
and potentially reserved cells,
rather than completely new ones.
Beyond that, blastemas and limb buds
have the same mission:
to make thousands of new cells
and organize them
into the muscle, bone, skin,
and nerve tissue
required for a functional limb.
As this process unfolds, nerves and
blood vessels spanning the injury site
transmit nutrition and oxygen.
Over several weeks,
the stump will steadily grow
a miniature limb with translucent skin.
And when the process is complete,
not only will the limb match
the rest of the salamander,
there won't even be a scar.
The relationship between scarring
and regeneration
is just one of this processes’
many mysteries.
Scientists are still tracking
salamander cells on the molecular level
to determine how they revert from a
mature stage into a regenerative one.
And research into transplanting
blastema cells investigates
how other animals might replicate
this reconstructive wizardry.
We also don’t understand how
salamanders’ bodies know
what part of the limb has been lost
or how much needs to be regrown.
One theory is that blastema cells have
a form of positional memory,
allowing them to determine how much
to grow in relation to one another.
And it’s equally important to understand
how these limbs know when to stop growing
to prevent overdevelopment,
like in cancerous tumors.
But one of regenerations essential
ingredients doesn’t belong solely
to salamanders:
the blastema.
Deer antlers use a similar healing
tissue to regenerate each year,
even though their skin scars like ours.
Spiny mice can also restore skin, hair,
and some other appendages scar-free.
And even humans can regenerate
the tips of our fingers and toes
in a surprisingly similar manner.
We still don’t know whether
this ability is tied
to our shared ancestry with salamanders
or fueled by distinct
biological mechanisms.
But with time and research,
who knows what evolutionary knowledge
we might grow back.
