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Tissue / Organ / Limb Regeneration

ted_bloody_maul

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'Miracle mouse' can grow back lost limbs
August 28, 2005

'Miracle mouse' can grow back lost limbs

Jonathan Leake, Science Editor

SCIENTISTS have created a "miracle mouse" that can regenerate amputated limbs or badly damaged organs, making it able to recover from injuries that would kill or permanently disable normal animals.

The experimental animal is unique among mammals in its ability to regrow its heart, toes, joints and tail. The researchers have also found that when cells from the test mouse are injected into ordinary mice, they too acquire the ability to regenerate.

The discoveries raise the prospect that humans could one day be given the ability to regenerate lost or damaged organs, opening up a new era in medicine.

Details of the research will be presented next week at a scientific conference on ageing, Strategies for Engineered Negligible Senescence, at Cambridge University. Ellen Heber-Katz, professor of immunology at the Wistar Institute, an American biomedical research centre, says that the ability of mice at her laboratory to regenerate appears to be controlled by about a dozen genes.

She is still researching their exact functions, but it seems almost certain that humans have comparable genes. "We have experimented with amputating or damaging several different organs, such as the heart, toes, tail and ears, and just watched them regrow," she said. "It is quite remarkable. The only organ that did not grow back was the brain. "When we injected foetal liver cells taken from those animals into ordinary mice, they too gained the power of regeneration. We found this persisted even six months after the injection." Heber-Katz made her discovery when she noticed that the identification holes that scientists punch in the ears of experimental mice healed without any signs of scarring.

The self-healing mice, from a strain known as MRL, were then subjected to a series of surgical procedures. In one the mice had their toes amputated - but the digits grew back, complete with joints.

In another test some of the tail was cut off but also regenerated. Then the researchers used a cryoprobe to freeze parts of the animals' hearts, only to see these grow back again. A similar phenomenon was observed when the optic nerve was severed and the liver partially destroyed.

Heber-Katz will describe some of her findings at the Cambridge conference and plans to publish her results in a research paper. "We have found that the MRL mouse seems to have a higher rate of cell division," she said. "Its cells live and die faster and get replaced faster. That seems to be linked to the ability to regenerate." The researchers suspect that the same genes could confer greater longevity and are measuring the animals' survival rate. The mice are, however, only 18 months old and the normal lifespan is two years so it is too early to reach conclusions.

Scientists have long known that less complex creatures have an impressive ability to regenerate. Many fish and amphibians can regrow internal organs or even whole limbs.

Humans can regenerate their liver provided at least a quarter remains intact, as well as their blood and outer skin, but no other organs regrow.

This is probably because, although most mammalian cells start off with the potential to develop into any cell type, they soon become very specialised. This allows mammals to develop more complex brains and bodies but deprives them of the power of regeneration.

By contrast, if a newt loses a limb then cells around the injury revert back into so-called stem cells. These can develop into whatever types of cell are needed, including bone, skin or nerves.

http://www.timesonline.co.uk/article/0, ... 08,00.html
 
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If they're making them indestructable someone will really need to build a better mousetrap.

If they ever get to applying this sort of technique to humans I can see possible pitfalls, increasing your rate of cell division could lead to a higher risk of cancer, for example.

Still it's a fascinating new development.
 
I am, this could be regarded as a fault, very sceptical/cynical of this claim.
It doesn't add up at all. Not without any famously miraculous scientific intervention anyway. Am I just too sheltered to have only read about it on the net? lol!
 
this is going to make the tom and jerry cartoons seem like the work of a prophet. :lol:
 
I'm going to have to look into this more carefully- but my initial reaction is that you're right it doesn't add up.
 
Turning the right genes on and off... perfectly plausable result.

I can't wait to see what else they can figure out by turning other genes on and off in the myriad combinations that are available.

What if they find the genes responsible for turning off the production of cancer cells - for each type of cancer?

Or if they find a way to turn off the genes that lead to production of bodily chemicals and hormones that may be responsible for aggresssive or psychotic behaviour?

Marvellous potential there...
 
MaxMolyneux asked if longevity would be affected;


The researchers suspect that the same genes could confer greater longevity and are measuring the animals' survival rate. The mice are, however, only 18 months old and the normal lifespan is two years so it is too early to reach conclusions.
 
coldelephant said:
Turning the right genes on and off... perfectly plausable result.

I can't wait to see what else they can figure out by turning other genes on and off in the myriad combinations that are available.

What if they find the genes responsible for turning off the production of cancer cells - for each type of cancer?

Or if they find a way to turn off the genes that lead to production of bodily chemicals and hormones that may be responsible for aggresssive or psychotic behaviour?

Marvellous potential there...
Er...............If you are a Nazi. This stuff has been going on doing the rounds for many a year and nothing substantial has ever come of it.
Or if they find a way to turn off the genes that lead to production of bodily chemicals and hormones that may be responsible for aggresssive or psychotic behaviour?
or the 'gay gene' or the 'blue eyed gene' etc..... Marvellous yeah.
 
Keelibibi wrote

Er...............If you are a Nazi

Nazi?

Bit OTT ;)

Anyway - genes are said by people to control what cells grow and what hormones are produced etc.

So if you turn off a group of genes responsible for say, producing a certain kind of cell - would you not expect that cell to stop being produced?

Why is this not plausible?

or the 'gay gene' or the 'blue eyed gene' etc..... Marvellous yeah

Also, as regards stopping aggressive or psychotic behaviour, why not?

Why would that be something you would object to?
 
Interesting, reminds me of Gattaca. To modify genes to prevent disease and suffering cant be bad. Can it? It does open up a rather large can of worms though.

or the 'gay gene' or the 'blue eyed gene' etc..... Marvellous yeah.

Its modifications like that which i feel should be left to mother nature. Where would the line be drawn?
 
Draw the line at the very begining. 'Turning off' genes which are natural is wrong in so many ways because it upsets the balance of natural selection. We need people who are aggressive, we need mutations and variations whether good or bad because without them, we would not be here in the first place. They are essential to the make up of society and understanding how we work.
The "...If you are a Nazi." Comment meant that it is a marvellous potential for doing what the Nazis set out to do. Breeding a 'master race'. Not a personal jibe my friend.
Hitler and his gullibles misinterpreted Darwin when he said the survival of the fittest, he meant the fittest as in those capable of adapting, not the physically supreme. Idiots. :lol:

Edited for bad spellings. (I'm on my monthly sorry) :(
 
Draw the line at the very begining. 'Turning off' genes which are natural is wrong in so many ways because it upsets the balance of natural selection.

I see what your saying but natural selection doesn't always mean the weak/vulnerable in our society will be just left to die and hence the next generation will be stronger/better. We look after the weak/vulnerable/needy. Im not saying i agree or disagree wholeheartedly with either argument as there are strong cases for both sides.
 
There are moral choices to make, sure.

Thing is, there is all this hype about the benefits of mucking around with genes etc - and questions about whether or not mucking around with genes will deliver what is speculated it could.

The moral debate will follow however, for example - in the wild, the weak would die or mutate and adapt in a previously unforseen way, happens all the time. Remember the story about the new species of dolphin?

One of the benefits of natural selection is population control - but seeing as we seem to have side stepped the rules regarding population control, other things have resulted. Now, even if there was a massively huge spread of a virus or disease, it would not make much of a difference to the human population; there is AIDS for example - but the population is over six billion and rising.

If we make ourselves stronger as a species, it will only mean we are going to allow our population to live longer and increase in number - is that morally right?

There again, if we posess the means to stop a group of people from attacking a girl and ripping off her skin, hair, beating her and setting her on fire - would we be morally correct not to muck about with genes and prevent such people from being unleashed upon civillised society?
 
It's looking increasingly like very many multi-level diseases like Alzheimer's for instance, will never be cured by any other means than gene therapy. And it's with an eye on this that scientists are now investing much time charting the gene(s) that can go wrong. When the technology becomes available to put that knowledge into action it will have untold potential.

I'm not sure I agree about the natural selection POV, in the case of Alzheimer's, which afflicts mainly the elderly, and does not kill until very advanced...I know it's only one example but this and quite a few other afflictions have nothing to contribute to natural selection, only to misery. I appreciate the fears of potential misapplication and there's great scope for that but let's face it, like stem cell research etc. it's going to happen whether we like it or not. And, as said, there will be big moral choices to be made.

PS I don't want to see this thread end up being derailed into a conflab about the ethical rights and wrongs of research. I'm sure it's been done a million times before and I don't want to read it. I am merely presenting here a point of view and I have no real axe to grind one way or t'other. If I get pounced on like I did in the last thread I contributed to, I'm pissing off.
 
Don't piss off. Simply turn off the genes that make you want to when jumped upon. :lol:
Joking. I agree with you there.
My main concern is that it is a load of bunkem. A bit like cold fusion and other things I won't mention because some people will dissagree.
There are benefits, I can clearly see that, but my cynical side cannot help but think that the crux of this research and its resulting use would be something sinister rather like new technologies being based upon military research. Use it for dastardly deeds first, then let the commercial consumer have some watered down bi-product with a friendly smile on the box or a tired NHS crew complacently administering it.


Spelling again. Sorry.
 
Hey - that's true.

They could end up spraying a load of nanomites from high up, and these could crawl into our skin and release a chemical that would turn certain genes on and off and we would die a horrible and painful death.

Beats 'The Terminator' doesn't it?
 
Insight into mystery of antlers

Stem cells play a key role in the deer's remarkable ability to grow new antlers, according to research.

The deer is unique among mammals in being able to regenerate a complete body part - in this case a set of bone antlers covered in velvety skin.

Experts at the Royal Veterinary College hope the work could one day lead to new ways to repair damaged human tissues.

Details were outlined in an edition of the BBC TV programme Super Vets, which was screened on 12 January.

Professor Joanna Price of the Royal Veterinary College said: "The regeneration of antlers remains one of the mysteries of biology but we are moving some way to understanding the mechanisms involved.

"Antlers provide us with a unique natural model that can help us understand the basic process of regeneration although we are still a long way from being able to apply this work to humans."

Mating game

Antlers are large structures made from bone that annually grow, die, are shed and then regenerate.

They grow in three to four months, making them one of the fastest growing living tissues.

After the antlers have reached their maximum size, the bone hardens and the velvety outer covering of skin peels off.

Once the velvet is gone, only the bare bone remains - a formidable weapon for fighting.

At the end of the mating season, the deer sheds its antlers to conserve energy. Next spring, a new pair grows out of a bony protuberance of tissue at the front of the animal's head.

Hormone link

The research suggests that stem cells - the master cells of the body, with the ability to develop into many specialised cell types - underpin this process.

It is mediated by some sort of signalling pathway, probably regulated by hormones such as oestrogen and testosterone.

The long-term goal of the work is to better understand the chemical signalling pathway behind the process of regeneration, in the hope that it can be harnessed by human medicine to develop novel treatments for diseases such as Parkinson's.

"If we know why this animal can do it whereas other mammals can't, we can start to say: 'Can we make this signal come on again if we have an injured or severed (human) tissue?'" Professor Price told the BBC News website.

------------------
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/s ... 598896.stm

Published: 2006/01/12 20:00:39 GMT

© BBC MMVI
 
The Scariest Ideas in Science
Laura Allen. Illustrations by Michael Koelsch

Maybe we saw The Andromeda Strain a few too many times in our formative years, but we can’t help shivering when we hear about microbiologists reanimating long-dormant lethal viruses. And those biologists working to make human limbs grow back: Haven’t we seen that film? Don’t the guys in lab coats all die in the first reel? They may sound cinematic, but the incredible research projects on the following pages are not imaginary. They’re real, funded ventures by respected scientists. They have perfectly rational goals. They also happen to creep us out. ...

Grow New Appendages

Amphibians can regenerate limbs. Mammals can’t. “This is a significant problem,” says Tulane University cell biologist Ken Muneoka. Now two teams of bioscientists are out to correct our evolutionary shortcoming under a recent $7.6-million Darpa grant. The current goal is to produce a mammalian blastema—the cell bud that forms a new amphibian limb. In four years, Darpa wants a regrown mouse finger. Human research is the logical next step.

WHY, GOD? WHY? The percentage of American combat amputees has doubled since the Korean War—a side effect of advancements in body armor and field medicine. Darpa funds will help scientists bolster preexisting research on the genetic and cellular processes of tissue regeneration. “Even if we fail,” says Muneoka, a team leader, “we’ll get better wound-healing.”

FEAR FACTOR As unnatural as the project sounds (“No, really, I have two left feet”), it doesn’t require genetic meddling, says the other team leader, Stephen Badylak of the University of Pittsburgh’s McGowan Institute for Regenerative Medicine. “The genes we need are there.” Mammals can already regrow limbs—to a point. Young children who lose fingertips can remake bone and tissue perfectly.

The teams are following even more curious leads. The regenerative abilities of the “MRL” breed of lab mouse, discovered by immunologist Ellen Heber-Katz of the Wistar Institute in Philadelphia, fall between those of amphibians and normal mammals. Holes punched in ears, cut tail tips, even injured heart tissue—all grow back (although when an MRL’s finger is cut lower than the tip, Heber-Katz says, “it’s able to form a structure but not the full digit”).

The research could be life-changing for amputees. The scientists believe that a mixture of cellular and extracellular components —maybe hormones, vita- min A, fibroblasts—could be applied to fresh amputations to steer them toward regeneration. “We grow a whole human in nine months,” Badylak says. “A limb should be nothing!” ...

www.popsci.com/popsci/science/b142d534c ... drcrd.html
 
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This 2010 Scientific American article describes how Heber-Katz's original interest in tissue regeneration / wound healing was fostered by an observation that could easily have been overlooked or ignored.
Case Closed: A Fluky Finding Raises Hopes for Mending Wounds

An amazing example of tissue regeneration in mice might lead to treatments that promote wound healing in humans--but it almost went unnoticed ...

https://www.scientificamerican.com/article/case-closed-wound-healing/
 
And those biologists working to make human limbs grow back: Haven’t we seen that film?

Why is this creepy? My one legged friend would be rather pleased if he had two.

And regeneration in Mammals is nothing new; Deer do it all the time.
 
In what may be a breakthrough, scientists have managed to stimulate regeneration of a leg in a frog species that (like humans) cannot normally regrow lost limbs.
New Treatment Helps Frogs Regenerate Limbs With Functioning Nerves in Just 18 Months

... While there have been significant advances in prosthetic and bionic technologies to replace lost limbs, they cannot yet restore a sense of touch, minimize the sensation of phantom pains or match the capabilities of natural limbs. Without reconstructing the limb itself, a person won't be able to feel the touch of a loved one or the warmth of the sun. ...

Our recent study in the journal Science Advances showed that just 24 hours of a treatment we designed is enough to regenerate fully functional and touch-sensitive limbs in frogs. ...

During very early development, cells that will eventually become limbs and organs arrange themselves into precise anatomical structures using a set of chemical, biomechanical and electrical signals.

In considering ways to regenerate limbs, we reasoned that it would be much easier to ask cells to repeat what they already did during early development. So we looked for ways to trigger the "build whatever normally was here" signal for cells at the site of a wound.

One of the major challenges in doing this, however, is figuring out how to create an environment that encourages the body to regenerate instead of forming scars. ...

Some aquatic animals such as the axolotl have mastered regeneration without scar formation. And even in early human development, the amniotic sac provides an environment that can facilitate regenerative mechanisms.

We hypothesized that developing a similar environment could override scar formation at the time of injury and allow the body to reactivate dormant regenerative signals.

To implement this idea, we developed a wearable device made of a silk hydrogel as a way to create an isolated chamber for regeneration by blocking other signals that would direct the body to develop scars or undergo other processes. We then loaded the device with a cocktail of five drugs involved in normal animal development and tissue growth.

We chose to test the device using African clawed frogs, a species commonly used in animal research which, like humans, does not regenerate limbs in adulthood.

We attached the device onto one leg stump for 24 hours. We then removed the device and observed how the site of the lost limb changed over time.

Over the course of 18 months, we were amazed to find that the frogs were able to regenerate their legs, including fingerlike projections with significant nerve, bone, and blood vessel regrowth. ...
FULL STORY: https://www.sciencealert.com/scient...help-frogs-regenerate-limbs-in-just-18-months

See Also:
Scientists Regrow Frog’s Lost Leg With a Five-Drug Cocktail
https://scitechdaily.com/scientists-regrow-frogs-lost-leg-with-a-five-drug-cocktail/

FULL RESEARCH REPORT: https://www.science.org/doi/10.1126/sciadv.abj2164
 
Axolotls continue to astound ... Recently published research indicates axolotls' abilities to regenerate neural tissues, structures, and connections represent a substantial capacity for re-growing damaged sections of their brains.
Axolotl weirdos can regrow their brains, and a new map reveals their regeneration secrets

The axolotl (opens in new tab) (Ambystoma mexicanum) is an aquatic salamander renowned for its ability to regenerate its spinal cord, heart and limbs (opens in new tab). These amphibians also readily make new neurons (opens in new tab) throughout their lives. In 1964, researchers observed that adult axolotls could regenerate parts of their brains (opens in new tab), even if a large section was completely removed. But one study found that axolotl brain regeneration (opens in new tab) has a limited ability to rebuild original tissue structure.

So how perfectly can axolotl’s regenerate their brains after injury? ...

Our team decided to focus on the telencephalon (opens in new tab) of the axolotl. In humans, the telencephalon is the largest division of the brain and contains a region called the neocortex (opens in new tab), which plays a key role in animal behavior and cognition. Throughout recent evolution, the neocortex has massively grown in size (opens in new tab) compared with other brain regions. Similarly, the types of cells that make up the telencephalon overall have highly diversified (opens in new tab) and grown in complexity over time, making this region an intriguing area to study. ...

We ... put axolotl regeneration to the test by removing one section of their telencephalon. Using a specialized method of scRNA-seq ... , we were able to capture and sequence all the new cells at different stages of regeneration, from one to 12 weeks after injury. Ultimately, we found that all cell types that were removed had been completely restored.

We observed that brain regeneration happens in three main phases. The first phase starts with a rapid increase in the number of progenitor cells, and a small fraction of these cells activate a wound-healing process. In phase two, progenitor cells begin to differentiate into neuroblasts. Finally, in phase three, the neuroblasts differentiate into the same types of neurons that were originally lost.

Astonishingly, we also observed that the severed neuronal connections (opens in new tab) between the removed area and other areas of the brain had been reconnected. This rewiring indicates that the regenerated area had also regained its original function. ...

... The brains of mice and humans have largely lost their capacity (opens in new tab) to repair or regenerate themselves. Medical interventions (opens in new tab) for severe brain injury currently focus on drug and stem cell therapies to boost or promote repair. Examining the genes and cell types that allow axolotls to accomplish nearly perfect regeneration may be the key to improve treatments for severe injuries and unlock regeneration potential in humans.
FULL STORY: https://www.livescience.com/axolotls-can-regenerate-their-brains


PUBLISHED RESEARCH REPORT:
Single-cell analyses of axolotl telencephalon organization, neurogenesis, and regeneration
KATHARINA LUST, ASHLEY MAYNARD, TOMÁS GOMES, JONAS SIMON FLECK, J. GRAY CAMP, ELLY M. TANAKA, AND BARBARA TREUTLEIN
SCIENCE 2 Sep 2022 Vol 377, Issue 6610
DOI: 10.1126/science.abp9262

Summary / Abstract: https://www.science.org/doi/10.1126/science.abp9262
 
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