A Tiny Surprise in Regards to Regeneration (A Guest Post)

A reposting of an original article by Jessica Klein in The Scorpion and the Frog.

The ability to regenerate limbs and tails is nothing new to reptiles and amphibians. Many lizards are able to drop their tails to escape an enemy, whereas salamanders have been known to grow back entire legs with muscle after being attacked by a predator. These regenerative characteristics have been seen to some extent in rabbits and pika before 2012, but were later discovered to occur extensively in, surprisingly enough, small African spiny mice.

One of the African spiny mouse species. Photo by Ashley Seifert and Tom Gawriluk.

In a study done by Ashley W. Seifert and Megan G. Seifert at the University of Kentucky, Todd M. Palmer and Malcolm Maden at the University of Florida, Stephen G. Kiama at the University of Nairobi, and Jacob R. Goheen at the University of Wyoming, African spiny mice were studied in order to view the extent of their regenerative properties, why they might occur, and the physiological processes that make it happen.

The rodents were captured in Kenya, where researchers learned that vigorous movement during handling caused the skin of African spiny mice to come apart. One mouse was reported to have an open wound that took up 60% of its back, just from being handled! Therefore, Dr. Seifert measured the amount of strength it took to tear the skin of spiny mice using something called a Hounsfield tensometer. He took the measurements from that tool and graphed them on a plot, creating something called a stress-strain curve which showed how much strength it took to tear the skin of the mouse.

The strength measurements revealed that the skin of these species was 77 times weaker than average mice, explaining why their skin tore so easily during the handling process. In order for the African spiny mice to survive such large injuries due to their extremely fragile skin, it would be beneficial to heal quickly or regenerate the skin. This is exactly what Dr. Seifert discovered.

An African spiny mouse shows
the regenerative process with
(1) being before the wound
(2) being after the wound and
(3) showing how the wound was
completely healed after 30 days.
Figure from Seifert, et al., 2012.

After the strength measurements were completed, the rodents were anaesthetized and had 4mm and 1.5cm wounds made on their skin, as well as 4mm holes punched in their ears in order to view the regeneration process. In an average rodent, the repair of a 4mm skin wound takes around 5 to 7 days and is accompanied by a significant amount of scarring. However, in the African spiny mouse it only took 1 to 2 days for scabbing of the skin wound to occur with new cells forming on the outside of the wound to repair it. After just 10 days, the ear of the mouse was fully healed. In the ear punches, there were no signs of scarring that would have been expected in a rodent, and healthy cartilage had formed. By the 21st day of the experiment, African spiny mice had developed new hair follicles and healthy new hair covering the once wounded area. In total, Dr. Seifert discovered that African spiny mice were capable of regenerating their skin, hair follicles, and sweat glands.

Dr. Seifert suggested the skin of African spiny mice is fragile because it allows them to escape predators. This would require a quick healing time to reduce the chance of infection and ultimately death in the mouse after escaping. This is why they may have gained the ability to regenerate their skin, but how exactly does this happen? Dr. Seifert and his research team recently showed that, in these species, it occurs through a process known as epimorphic regeneration. This is when a blastema (a mass of immature, unspecialized cells) forms where the wound once was. These cells are capable of turning into whatever type of tissue was present in that area. This particular method of regeneration is how salamanders are capable of regenerating their limbs. Again, more research would need to be done in order to confirm or deny this. However, one thing is true, and that is that more research into this could prove to be useful in the future of medicine when it comes to healing critical and invasive injuries. By discovering the physiological process behind this, and then being able to replicate it in a lab, researchers may discover ways to heal injuries faster.

Works Cited

Seifert, Ashley W., Stephen G. Kiama, Megan G. Seifert, Jacob R. Goheen, Todd M. Palmer, and Malcolm Maden. "Skin Shedding and Tissue Regeneration in African Spiny Mice (Acomys)." Nature 489 (2012): 561-65. doi:10.1038/nature11499

Gawriluk, Thomas R., Jennifer Simkin, Katherine L. Thompson, Shishir K. Biswas, Zak Clare-Salzler, John M. Kimani, Stephen G. Kiama, Jeramiah J. Smith, Vanessa O. Ezenwa & Ashley W. Seifert. "Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals" Nature Communications 7.11164 (2016). doi:10.1038/ncomms11164

Need a Hand? Just Grow it Back! How Salamanders Regenerate Limbs (A Guest Post)

By Maranda Cardiel

(A reposting of an original article posted on February 29, 2016)

How cool would it be if you could regenerate your own body parts? Just imagine: you are chopping up some carrots for dinner, but whoops! You accidentally cut off your thumb! No worries, it’ll grow back in a few weeks, good as new and fully functional. No need to take a trip to the hospital and pay all of those annoying medical costs.

That all sounds pretty nifty, but that can’t actually happen, right? Tissue regeneration on that large of a scale is something you can only find in science fiction. …Or so you may think. Nature has actually found a way to regenerate full limbs and other body parts after they have been completely amputated. However, among animals with spines, this unique ability is only found in salamanders. But how does it work, and why can’t we do it too?

A cartoon illustrating examples of the three different methods of tissue regeneration in animals. A.) An
adult hydra being cut into two pieces and regenerating into two separate hydras. B.) Part of a human
liver being cut off and the remaining liver regenerating via cell division. C.) A salamander’s arm being
amputated and undergoing epimorphosis to regenerate an entire new arm.
Source: Maranda Cardiel

There are actually three ways that animals can regenerate tissues. Some animals, such as hydras, can use the tissues they already have to regenerate themselves after being cut in two, resulting in two separate hydras. Mammals, including humans, have the ability to regenerate their livers by having the liver cells divide into more liver cells. This is how liver transplants work – a portion of liver from a live donor will grow into a fully-functioning liver in the recipient. The third method is called epimorphosis, which is the ability to change existing cells of specific types so that they can re-grow as different cell types, and this is what salamanders are able to do.

When the limb of a salamander is cut off, only the outermost layer of skin moves to cover the wound. This single layer forms a special skin cap known as the epithelial cap, and the nerves at the amputation site shrink back from the wound. Then the cells beneath the cap dedifferentiate, losing their specific characteristics so all of the different types of cells become the same and detach from each other.

A cartoon illustrating the process of a salamander regenerating its arm. A.) The limb is amputated.
B.) The outermost layer of the skin begins to cover the wound. C.) This single layer of skin creates
an epithelial cap and the blastema forms underneath it. D.) The cells of the blastema begin to
differentiate into bone, nerves, etc. E.) The cells continue to divide and differentiate until the limb is
fully formed. Source: Maranda Cardiel

Now the amputated limb has a mass of indistinguishable cells under the cap, and this mass is called the regeneration blastema. A blastema is simply a clump of cells that is able to grow into an organ or body part. Over the course of several weeks, this blastema divides into more cells and the cells begin to differentiate - or turn into multiple types - again, forming different cell types such as bone, muscle, cartilage, nerves, and skin. Eventually, the salamander will have a brand new limb.

The salamander’s body can even tell what body part it’s supposed to re-grow; if it’s amputated at the wrist it will grow a new hand, and if its entire hind leg is amputated it will grow a new hind leg. And it’s not only limbs that salamanders can regenerate – they can even grow back their tails, retinas, spinal cords, and parts of their hearts and brains!

As you can see, the process of epimorphosis is much more complicated than simply having a single cell type divide a lot. It also requires certain chemicals and patterns of immune signaling to work properly. But why can’t people do this too? One of the reasons is because when our tissues are damaged, all of our skin grows to cover and heal the wound, which forms scars. In salamanders, only the outermost layer of skin does this, which prevents the scarring that would stop tissue regeneration. The salamander’s immune system is also regulated differently than our own, which allows them to regenerate whole body parts.

Unfortunately we are not salamanders, so when you cut off your finger it’s not going to grow back. But researchers are continuing to study salamanders and their astounding regenerative abilities in the hopes of finding a way to apply it to people. Who knows, maybe someday we’ll be able to grow back our own limbs too.


Sources:

Gilbert, Scott F. Developmental Biology 6th Edition. Ncbi.nlm.nih.gov. National Center for Biotechnology Information, 2000.

Godwin, J., Pinto, A., & Rosenthal, N. (2013). Macrophages are required for adult salamander limb regeneration Proceedings of the National Academy of Sciences, 110 (23), 9415-9420 DOI: 10.1073/pnas.1300290110

A Tiny Surprise in Regards to Regeneration (A Guest Post)

By Jessica Klein

The ability to regenerate limbs and tails is nothing new to reptiles and amphibians. Many lizards are able to drop their tails to escape an enemy, whereas salamanders have been known to grow back entire legs with muscle after being attacked by a predator. These regenerative characteristics have been seen to some extent in rabbits and pika before 2012, but were later discovered to occur extensively in, surprisingly enough, small African spiny mice.

One of the African spiny mouse species. Photo by Ashley Seifert and Tom Gawriluk.

In a study done by Ashley W. Seifert and Megan G. Seifert at the University of Kentucky, Todd M. Palmer and Malcolm Maden at the University of Florida, Stephen G. Kiama at the University of Nairobi, and Jacob R. Goheen at the University of Wyoming, African spiny mice were studied in order to view the extent of their regenerative properties, why they might occur, and the physiological processes that make it happen.

The rodents were captured in Kenya, where researchers learned that vigorous movement during handling caused the skin of African spiny mice to come apart. One mouse was reported to have an open wound that took up 60% of its back, just from being handled! Therefore, Dr. Seifert measured the amount of strength it took to tear the skin of spiny mice using something called a Hounsfield tensometer. He took the measurements from that tool and graphed them on a plot, creating something called a stress-strain curve which showed how much strength it took to tear the skin of the mouse.

The strength measurements revealed that the skin of these species was 77 times weaker than average mice, explaining why their skin tore so easily during the handling process. In order for the African spiny mice to survive such large injuries due to their extremely fragile skin, it would be beneficial to heal quickly or regenerate the skin. This is exactly what Dr. Seifert discovered.

An African spiny mouse shows
the regenerative process with
(1) being before the wound
(2) being after the wound and
(3) showing how the wound was
completely healed after 30 days.
Figure from Seifert, et al., 2012.

After the strength measurements were completed, the rodents were anaesthetized and had 4mm and 1.5cm wounds made on their skin, as well as 4mm holes punched in their ears in order to view the regeneration process. In an average rodent, the repair of a 4mm skin wound takes around 5 to 7 days and is accompanied by a significant amount of scarring. However, in the African spiny mouse it only took 1 to 2 days for scabbing of the skin wound to occur with new cells forming on the outside of the wound to repair it. After just 10 days, the ear of the mouse was fully healed. In the ear punches, there were no signs of scarring that would have been expected in a rodent, and healthy cartilage had formed. By the 21st day of the experiment, African spiny mice had developed new hair follicles and healthy new hair covering the once wounded area. In total, Dr. Seifert discovered that African spiny mice were capable of regenerating their skin, hair follicles, and sweat glands.

Dr. Seifert suggested the skin of African spiny mice is fragile because it allows them to escape predators. This would require a quick healing time to reduce the chance of infection and ultimately death in the mouse after escaping. This is why they may have gained the ability to regenerate their skin, but how exactly does this happen? Dr. Seifert and his research team recently showed that, in these species, it occurs through a process known as epimorphic regeneration. This is when a blastema (a mass of immature, unspecialized cells) forms where the wound once was. These cells are capable of turning into whatever type of tissue was present in that area. This particular method of regeneration is how salamanders are capable of regenerating their limbs. Again, more research would need to be done in order to confirm or deny this. However, one thing is true, and that is that more research into this could prove to be useful in the future of medicine when it comes to healing critical and invasive injuries. By discovering the physiological process behind this, and then being able to replicate it in a lab, researchers may discover ways to heal injuries faster.

Works Cited

Seifert, Ashley W., Stephen G. Kiama, Megan G. Seifert, Jacob R. Goheen, Todd M. Palmer, and Malcolm Maden. "Skin Shedding and Tissue Regeneration in African Spiny Mice (Acomys)." Nature 489 (2012): 561-65. doi:10.1038/nature11499

Gawriluk, Thomas R., Jennifer Simkin, Katherine L. Thompson, Shishir K. Biswas, Zak Clare-Salzler, John M. Kimani, Stephen G. Kiama, Jeramiah J. Smith, Vanessa O. Ezenwa & Ashley W. Seifert. "Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals" Nature Communications 7.11164 (2016). doi:10.1038/ncomms11164

Need a Hand? Just Grow it Back! How Salamanders Regenerate Limbs (A Guest Post)

By Maranda Cardiel

How cool would it be if you could regenerate your own body parts? Just imagine: you are chopping up some carrots for dinner, but whoops! You accidentally cut off your thumb! No worries, it’ll grow back in a few weeks, good as new and fully functional. No need to take a trip to the hospital and pay all of those annoying medical costs.

That all sounds pretty nifty, but that can’t actually happen, right? Tissue regeneration on that large of a scale is something you can only find in science fiction. …Or so you may think. Nature has actually found a way to regenerate full limbs and other body parts after they have been completely amputated. However, among animals with spines, this unique ability is only found in salamanders. But how does it work, and why can’t we do it too?

A cartoon illustrating examples of the three different methods of tissue regeneration in animals. A.) An adult hydra being cut into two pieces and regenerating into two separate hydras. B.) Part of a human liver being cut off and the remaining liver regenerating via cell division. C.) A salamander’s arm being amputated and undergoing epimorphosis to regenerate an entire new arm.
Source: Maranda Cardiel

There are actually three ways that animals can regenerate tissues. Some animals, such as hydras, can use the tissues they already have to regenerate themselves after being cut in two, resulting in two separate hydras. Mammals, including humans, have the ability to regenerate their livers by having the liver cells divide into more liver cells. This is how liver transplants work – a portion of liver from a live donor will grow into a fully-functioning liver in the recipient. The third method is called epimorphosis, which is the ability to change existing cells of specific types so that they can re-grow as different cell types, and this is what salamanders are able to do.

When the limb of a salamander is cut off, only the outermost layer of skin moves to cover the wound. This single layer forms a special skin cap known as the epithelial cap, and the nerves at the amputation site shrink back from the wound. Then the cells beneath the cap dedifferentiate, losing their specific characteristics so all of the different types of cells become the same and detach from each other.

A cartoon illustrating the process of a salamander regenerating its arm. A.) The limb is amputated. B.) The outermost layer of the skin begins to cover the wound. C.) This single layer of skin creates an epithelial cap and the blastema forms underneath it. D.) The cells of the blastema begin to differentiate into bone, nerves, etc. E.) The cells continue to divide and differentiate until the limb is fully formed. Source: Maranda Cardiel

Now the amputated limb has a mass of indistinguishable cells under the cap, and this mass is called the regeneration blastema. A blastema is simply a clump of cells that is able to grow into an organ or body part. Over the course of several weeks, this blastema divides into more cells and the cells begin to differentiate - or turn into multiple types - again, forming different cell types such as bone, muscle, cartilage, nerves, and skin. Eventually, the salamander will have a brand new limb.

The salamander’s body can even tell what body part it’s supposed to re-grow; if it’s amputated at the wrist it will grow a new hand, and if its entire hind leg is amputated it will grow a new hind leg. And it’s not only limbs that salamanders can regenerate – they can even grow back their tails, retinas, spinal cords, and parts of their hearts and brains!

As you can see, the process of epimorphosis is much more complicated than simply having a single cell type divide a lot. It also requires certain chemicals and patterns of immune signaling to work properly. But why can’t people do this too? One of the reasons is because when our tissues are damaged, all of our skin grows to cover and heal the wound, which forms scars. In salamanders, only the outermost layer of skin does this, which prevents the scarring that would stop tissue regeneration. The salamander’s immune system is also regulated differently than our own, which allows them to regenerate whole body parts.

Unfortunately we are not salamanders, so when you cut off your finger it’s not going to grow back. But researchers are continuing to study salamanders and their astounding regenerative abilities in the hopes of finding a way to apply it to people. Who knows, maybe someday we’ll be able to grow back our own limbs too.


Sources:

Gilbert, Scott F. Developmental Biology 6th Edition. Ncbi.nlm.nih.gov. National Center for Biotechnology Information, 2000.

Godwin, J., Pinto, A., & Rosenthal, N. (2013). Macrophages are required for adult salamander limb regeneration Proceedings of the National Academy of Sciences, 110 (23), 9415-9420 DOI: 10.1073/pnas.1300290110