Regeneration

Zebrafish as models of human disease and drug development

dr. dolittle — Sat, 24 Jun 2017 23:25:25 +0000

Zebrafish as models of human disease and drug development

Photo of zebrafish housed at a research institute. By Karol Głąb CC BY-SA 3.0. via Wikimedia Commons

Who would have thought tiny fish could lead to big advances in medicine? Zebrafish (Danio rerio) and mammals have similar anatomy and physiology of the brain, eyes, gut, and cardiovascular systems. Some of the reasons why these fish are good models to understand cardiovascular physiology were recently explored in a new article published in Physiological Reviews.

Animal models are used in research that seeks to understand both normal physiological mechanisms as well as mechanisms related to disease. Because of their small size, zebrafish are easy to house in a laboratory. Studies of early development can also be easily performed using zebrafish embryos as they are transparent and develop externally. Their relatively short lifespans along with recent advances in the ability to alter genes allow for rapid examination of the effects of genetic mutations on development.

The focus of the review article written by Gut et al., was on the usefulness of zebrafish as models for cardiovascular and metabolism-related diseases. I was impressed to find out that zebrafish and humans share similar electrical patterns (EKG) of the heart as well as heart rates of 60-100 beats per minute (as compared to mice with heart rates around 600 beats/min). They also experience some of the same pathologies related to electrical conduction in the heart. In addition, the zebrafish heart expresses 96% of the genes that are associated with cardiomyopathy in humans, making them useful models in which to improve understanding as well as develop new therapies for heart disease. What is most unique about the zebrafish heart, however, is that it can regenerate. Researchers are hoping to unlock the secrets of this process in order to help regenerate hearts that have been damaged by heart attacks. Although given the relative simplicity of the zebrafish heart, this may prove challenging.

Similar to humans, researchers have found that feeding zebrafish a fat-enriched diet promotes the development of obesity, insulin resistance, fatty liver disease as well as atherosclerosis. Research has led to the discovery of how a gene that is associated with risk for developing type 2 diabetes is involved in regulating where fats are stored in the body. Another advantage to zebrafish is the discovery of a similar mechanism that causes atherosclerosis as in humans, whereas rodents do not develop the disease unless genetically manipulated. Similar to the heart, insulin-producing cells of the zebrafish pancreas are capable of regenerating, which researchers hope may lead to new therapies for the treatment of type 1 diabetes.

Zebrafish have also proved useful models in which to examine the re-purposing of old drugs as well as the creation of new drugs for the treatment of bone-related diseases, as well as cancer, multiple sclerosis, and epilepsy, just to name a few.

Source:

P Gut, S Reischauer, DYR Stainier, R Arnaout. Little Fish, Big Data: Zebrafish as a Model for Cardiovascular and Metabolic Disease. Physiological Reviews. Published 3 May 2017, Vol. 97, no. 3, pages 889-938. DOI: 10.1152/physrev.00038.2016

dr. dolittle Sat, 06/24/2017 - 19:25

Tags

Reindeers may pave way for discovery of nerve regeneration techniques for humans

dr. dolittle — Wed, 07 Dec 2016 15:16:54 +0000

Reindeers may pave way for discovery of nerve regeneration techniques for humans

I came across a neat article in Scientific American that described how reindeer and elk regrow their antlers every year. Could you imagine putting that much energy into growing new bone each year complete with a velvety cover containing nerves, skin, and blood vessels? Although full-grown antlers lose their blood supply and animals scrape the velvet layer off to reveal just bone.

Researchers have explored whether understanding this amazing process of annual antler regeneration could lead to new therapies to regrow nerves or organs in humans. The nerve fibers that innervate the antlers in deer originate from the trigeminal nerve. These sensory fibers grow at an impressive rate of up to 2 cm every day! The nerves are located in the velvet that covers the external surface of the antlers and they are closely associated with skin and the blood supply, which gives them access to nutrients and molecules that can help guide their growth. The cartilage and bone are found internally. The antlers grow annually from a base of sorts, called the pedicle. The pedicle is a permanent growth on the frontal bone which has been found to contain stem cells that are responsible for creating the internal components of the antlers. It is thought that the external components, including the blood supply and nerves are stimulated to grow by chemical signals and perhaps mechanical cues from the growth of the internal components. Dr. Li from the AgResearch Invermay Agricultural Center in New Zealand, has suggested that identifying these chemical signals may lead to new discoveries in organ regeneration for humans.

To learn more about how these animals regrow antlers, check out this video:

Sources:

Li C. Deer antler regeneration: A stem cell-based epimorphic process. Birth Defects Research C Embryo Today. 96(1): 51-62, 2012.

Nieto-Diaz M, Pita-Thomas DW, Munoz-Galdeano T, Martinez-Maza C, Navarro-Ruiz R, Reigada D, Yunta M, Caballero-Lopez MJ, Nieto-Sampedro M, Martinez-Maza R. Deer antler innervation and regeneration. Frontiers in Bioscience. 17:1389-1401, 2012.

Scientific American

dr. dolittle Wed, 12/07/2016 - 10:16

Tags

Limb regeneration in brittle stars

dr. dolittle — Sat, 30 Apr 2016 18:12:06 +0000

Limb regeneration in brittle stars

Image of brittle star by Jerry Kirkhart from Los Osos, Calif. [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons

A new study published in Frontiers in Zoology examined the developmental process involved in regulating limb regeneration in brittle stars (Amphiura filiformis) following amputation of an arm. Limb regeneration is a multi-stage process involving initial healing and repair of the wounded site, initial growth of the limb followed by development of more complex layers of cells until ultimately the limb has been fully regenerated. Understanding this process in brittle stars may lead to better understanding of limb regeneration in other echinoderms or at least methodologies that can examine the process in other animals.

The ability for brittle stars to regenerate limbs so readily is more than likely an adaptation to avoid predation.

Source:

A Czarkwiani, C Ferrario, DV Dylus, M Sugni, P Oliveri. Skeletal regeneration in the brittle star Amphiura filiformis. Frontiers in Zoology. 13:18, 2016. DOI: 10.1186/s12983-016-0149-x

dr. dolittle Sat, 04/30/2016 - 14:12

Tags

“The ability for brittle stars to regenerate limbs so readily is more than likely an adaptation to avoid predation.”

Dear Dr. Dolittle,

Why didn’t we human’s adapt this same survival-enhancing ability?

What do you do with your time when you’re not writing science fiction?

"Why didn’t we human’s adapt this same survival-enhancing ability?"

Well, you dishonest little science denier, why don't try to do some research and find out?

Oh, because that would require work on your part? I forgot, you're a fundamentalist and creationist - work and education aren't things your type do.

Ask the Experts: Growing new limbs

dr. dolittle — Thu, 13 Nov 2014 17:19:27 +0000

Ask the Experts: Growing new limbs

A reader sent me the following question:

"How does a lizard grow a new tail?"

This was a very timely question as new research has shed light on this very phenomenon. A team of experts at Arizona State University led by Dr. Kenro Kusumi and colleagues have been studying limb regeneration in lizards.

Green anole lizard (Anolis carolinensis) with tail a new tail (image credit: Hutchins et al./PLoS ONE)

The green anole lizard (pictured above) can lose its tail when captured by a predator. They are then able to regrow their tails, although they do not look quite like the original. Dr. Kusumi's team characterized the genes that are turned on during this regeneration process.

According to Dr. Kusumi, "Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing.”

While frog tadpoles and fish can likewise regrow the tips of their tails, lizard regrowth is not limited to the tip, but rather appears to be distributed throughout the length of the tail. Study co-author Elizabeth Hutchins (a graduate student at Arizona State University who contributed to this research) said that it can take more than 60 days for a lizard to regrow a functional tail.

The implications for this research in developing methods to regrow limbs in humans is pretty exciting! Dr. Kusumi mentioned, "Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail. By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future."

Sources:

Arizona State University Press Release

Hutchins ED, Markov GJ, Eckalbar WL, George RM, King JM, Tokuyama MA, Geiger LA, Emmert N, Ammar MJ, Allen AN, Siniard AL, Corneveaux JJ, Fisher RE, Wade J, DeNardo DF, Rawls JA, Huentelman MJ, Wilson-Rawls J, Kusumi K. Transcriptomic Analysis of Tail Regeneration in the Lizard Anolis carolinensisReveals Activation of Conserved Vertebrate Developmental and Repair Mechanisms. PLOS ONE. 9(8): e105004. doi:10.1371/journal.pone.0105004

dr. dolittle Thu, 11/13/2014 - 12:19

Tags

Last Week on ResearchBlogging.org

milhayser — Sun, 02 Mar 2014 10:29:55 +0000

Last Week on ResearchBlogging.org

Solar cells made with bismuth vanadate achieve a surface area of 32 square meters per gram. This compound can be paired with cheap oxides to split water molecules (and make hydrogen) with record efficiency.

Short-term geoengineering could postpone global warming, only to have it happen more quickly in the future.

Carotenoids tinge blackbird bills a deep orange, signalling fitness; birds with oranger bills are "are heavier and larger, have less blood parasites and pair with females in better condition than males with yellow bills."

Fibroblasts can extrude a tidy biological scaffold for stem-cell growth at a nanometer scale, while provoking a lower immune response than synthetic or animal-derived materials.

Higher levels of Omega-3 fatty acids in the blood correlate with stronger white matter in the brain.

By first reverting skin cells to endodermal cells instead of stem cells, researchers were able to transform them into better liver cells with true regenerative potential.

Headband cam reveals that babies spend 25% of their waking lives looking at other people's faces, 96% of which belonged to members of their own race. By the age of 6 months, the faces of another race begin to all look the same.

Here: everything you ever wanted to know about star spiders.

Rodents are similar enough to humans to be used as laboratory models, so does a cat parasite that manipulates the behavior of rats also alter the behavior of humans (30-40% of whom are infected worldwide)?

Researchers have come within 99.8% of the theoretical limit of light absorption enhancement in solar cells, paving the way for "the next generation of high-efficiency, cost-effective and ultra-thin crystalline silicon solar cells."

European utilities, under pressure from a law requiring 20% of all energy to come from renewable sources by 2020, are importing millions of metric tons of wood pellets from the southern United States. Burning these pellets produces less than half the emissions of fossil fuel, not counting the energy needed to ship them across the Atlantic.

Newly discovered chimpanzee populations in the Congo are thriving, outnumbering their cousins in West Africa, but bushmeat hunters, like researchers, are beginning to encroach.

Another study shows a correlation between use of acetaminophen (i.e. Tylenol) during pregnancy and the development of ADHD in children.

New process turns algae into biogas compatible with our natural gas infrastructure. "While it takes nature millions of years to transform biomass into biogas, it takes the SunCHem process less than an hour."

Among single-celled organisms like algae, programmed suicide can benefit relatives while suppressing the growth of non-relatives.

Off-shore wind turbines could significantly slow hurricane winds and decrease storm surges, all while generating electricity.

Novel aerogel made from wood and polymer could be thrown on an oil spill, absorbing nearly 100 times its own weight before being wrung out and used again.

Five-year-olds spanked by their mothers showed increased behavioral problems at age 9. Those spanked by their fathers showed reduced vocabulary.

During a musical "conversation," a jazz musician scanned by fMRI showed activation of language and rhythmic centers in the brain, hemispheric mirrors that "perform syntactic processing for both music and speech." At the same time, there was a marked deactivation of the angular gyrus, which is involved in interpreting the meaning of words if not their syntactic structure.

And finally if you want to be considered a great artist, it might be worth cultivating an eccentric persona in the most sincere manner possible.

For more visit researchblogging.org.

milhayser Sun, 03/02/2014 - 05:29

How research in fruit flies may help to repair brain injuries in humans

dr. dolittle — Sat, 01 Mar 2014 00:31:00 +0000

How research in fruit flies may help to repair brain injuries in humans

Artist's rendition of dendrite regeneration in a fruit fly during metamorphosis. (Chay Kuo Lab, Duke University)

Researchers at Duke University are interested in understanding the metamorphosis of fruit flies from larvae to adult stage in an effort to understand how the insects grow new nerve endings as they undergo this transition. What is interesting is that the flies lose neurons they will not need as an adult and will grow new nerve endings. According to a press release from Duke University, a protein called Cysteine proteinase-1 (Cp1) is important in the regeneration step. In fact, their study found that fruit fly nerves cannot regenerate in the absence of this protein.

Since humans are not able to regenerate damaged neurons, the goal is to eventually help humans with brain injuries grow new neurons.

Sources:

Kentaro Kato, Alicia Hidalgo. An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila. JOVE 73: e50306, 2013.

Gray R. Lyons, Ryan O. Andersen, Khadar Abdi, Won-Seok Song, and Chay T. Kuo. Cysteine Proteinase-1 and Cut Protein Isoform Control Dendritic Innervation of Two Distinct Sensory Fields by a Single Neuron. Cell Reports, March 13, 2014. DOI: 10.1016/j.celrep.2014.02.003.

dr. dolittle Fri, 02/28/2014 - 19:31

Tags

Hi Dr. Dolittle I hope this research will be finished soon, This is going to be so useful and can help those patient who suffered from head/brain injury.

Doh! John McCain and Sarah Palin got it wrong again...

Request more detail info since my grandson has TBI and needs help.

Dear Hector,

I am very sorry to hear about your grandson. While this research is not able to directly benefit humans just yet, here are some links from the CDC and National Institutes of Health on current practices for treating TBI that you and your family may find helpful in your discussions with his physician(s).
http://www.cdc.gov/concussion/get_help.html
http://www.ninds.nih.gov/disorders/tbi/tbi.htm#Is_there_any_treatment

In addition, drug companies are currently studying the effectiveness of cysteine protease inhibitors in the treatment of TBI.
http://www.ncbi.nlm.nih.gov/pubmed/24083575

I hope this helps.

Dr. Dolittle

it's very interesting research Dr. Dolittle.
I'm waiting ...
Aile Terapisti Uğur

I find this quite interesting. But am also compelled to ask about possible future applications in areas other than the brain. Are they also looking into applications on for instance paralyses due to damage to or underdevelopment of nerve tissue in other areas?

This is an interesting and could potentially be the cure or prevention to many fatal mental diseases such as Alzheimer's disease. I see in the paragraph posted by Doctor they say the flies are unable to regenerate new neurons in the absence of the protein (Cysteine proteinase-1 (Cp1)) I'm not sure if humans are able to code for this protein but should we not maybe with the same biotechnology used in manufacture of Insulin we will be able to in the future inject this protein into humans and it too could aid in the regeneration of new neurons in humans. Also with more understanding and research of how exactly the regenaration process happens scientists could come up with another break through in medicine.

This i quite intriguing . This discovery will result in evolution in medical sciences, bringing new technologies and sciences to save lives

Good article once again. Research into this seems to be quite necessary, as having technology that could use this idea potentially would change the living standards of millions of people/families. Definitely something we should be focusing on as future scientists.

This is amazing.This discovery can result in evolution in medical sciences, bringing new technologies and sciences to save lives

African rodent species resist scarring

dr. dolittle — Fri, 28 Sep 2012 13:40:04 +0000

African rodent species resist scarring

You might be familiar with tissue regeneration in amphibians and reptiles where limbs can be fully regenerated following an injury. Until now, tissue regeneration following a wound was thought to be limited in mammals (ex: deer shed and regrow their antlers annually; some mice can regrow the tips of their fingers).

Researchers discovered that African spiny mice are able to regrow skin, complete with hair follicles, after an injury. We are not talking about simple wound healing, but actual skin regeneration without scarring. Researchers suspect this unique ability may have evolved to help them avoid predators since they are capable of shedding large patches of skin to escape. Researchers found their skin to be less elastic than laboratory mice (M. musculus), increasing its susceptibility to tearing. Sometimes the tears are so deep, the muscles below become exposed.

A transdermal injury at day 3. Figure from: Nature doi: 10.1038/nature11499

Transdermal injury at day 30. Figure from Nature doi: 10.1038/nature11499

The researchers found that epithelial cell migration to the site of injury was much faster in the African mice. The collagen fibers also organized into loose bundles, preventing scarring. In contrast, collagen fibers in laboratory mice form dense, organized bundles that promote scars. Moreover, the African mice actually regrow hair follicles, whereas laboratory mice do not. Not only can the animals regrow torn skin, but they are also able to heal holes pierced into their ears complete with cartilage, hair follicles, skin, sebaceous glands and fat without scarring, although the regrown tissue lacked muscle. This ear regeneration is regulated by specialized cells called blastema that are similar to those found in lizards capable of regrowing tails.

Researchers hope this research will help to better understand tissue regeneration, as opposed to scarring, capabilities in mammals.

This research reminds me of the futuristic technology in Star Trek episodes, where they use light to heal wounds with minimal scarring.

Source:
Seifert AW, Kiama SG, Seifert MG, Goheen JR, Palmer TM, Maden M. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature. 489:561-566, 2012.

dr. dolittle Fri, 09/28/2012 - 09:40

Tags

Could the Ways in Which Animals Regenerate Hair and Feathers Lead to Clues for Restoring Human Fingers and Toes?

dr. dolittle — Thu, 31 May 2012 14:11:29 +0000

Could the Ways in Which Animals Regenerate Hair and Feathers Lead to Clues for Restoring Human Fingers and Toes?

On a recent visit to The American Physiological Society's website, I found this amazing story on regeneration that I thought you might enjoy:

This summer’s action film, “The Amazing Spider-Man™,” is another match-up between the superhero and his nemesis the Lizard. Moviegoers and comic book fans alike will recall that the villain, AKA Dr. Curt Connors, was a surgeon who, after losing an arm, experimented with cell generation and reptilian DNA and was eventually able to grow back his missing limb. The latest issue of the journal Physiology contains a review article that looks at possible routes that unlock cellular regeneration in general, and the principles by which hair and feathers regenerate themselves in particular. The authors apply what is currently known about regenerative biology to the emerging field of regenerative medicine, which is being transformed from fantasy to reality.

The Review is entitled “Physiological Regeneration of Skin Appendages and Implications for Regenerative Medicine” (http://bit.ly/IGC6mP) and was written by Cheng-Ming Chuong, Randall B. Widelitz, Ping Wu, and Ting-Xin Jiang of the University of Southern California, and Valerie A. Randall of the University of Bradford. It appears in the current edition of Physiology, published by the American Physiological Society.

Review Article

While the concept of regenerative medicine is relatively new, animals are well known to remake their hair and feathers regularly by normal regenerative physiological processes. In their review, the authors focus on (1) how extrafollicular environments can regulate hair and feather stem cell activities and (2) how different configurations of stem cells can shape organ forms in different body regions to fulfill changing physiological needs.

The review outlines previous research on the role of normal regeneration of hair and feathers throughout the lifespan of various birds and mammals. The researchers include what is currently known about the mechanism behind this re-growth, as well as what gaps still exist in the knowledge base and remain ripe for future research.

The review examines dozens of papers on normal “physiological regeneration”—the re-growth that happens over the course of an animal’s life and not in response to an injury. This regeneration takes place to accommodate different stages in an animal’s life (e.g., replacing downy chick feathers with an adult chicken’s, or replacing the fine facial hair of a young boy with the budding beard of an adolescent), or in response to various environmental conditions (e.g., cats shedding a thick winter coat in the summer heat but re-growing it when the seasons change again, or snowshoe hares switching from brown in the summer to white in the winter for camouflage). These changes seem to respond both to internal cues such as physiology of the hair follicle itself, or external cues such as the environment, but the mechanisms behind these normal alterations are largely unknown. Stem cells inside the follicle prompt hair and feather regeneration, but researchers are still unsure how to guide those cells to form the shape, size, and orientation of these “skin appendages” so that controlled re-growth is possible. Additionally, scientists are still unsure how to re-grow hair on skin in people after severe injuries that lead to scar tissue.

Importance of the Findings

The reviewed studies suggest that while researchers are making headway in understanding how and why hair and feathers regenerate after normal loss or in response to different life stages, much still remains unknown. This missing knowledge could hold valuable clues to learning how to regenerate much more complicated and valuable structures after loss to injury, such as fingers and toes.

“Using the episodic regeneration of skin appendages as a clear readout, we have the opportunity to understand and modulate the behavior or adult stem cells and organ regeneration at a level heretofore unknown,” the authors say.

dr. dolittle Thu, 05/31/2012 - 10:11

Tags

TEDTalks: Anthony Atala Talks about Growing Human Organs at TEDMED

grrlscientist — Fri, 22 Jan 2010 05:59:43 +0000

TEDTalks: Anthony Atala Talks about Growing Human Organs at TEDMED

tags: Growing Organs, medicine, TEDMED,regeneration, stem cells, organ, tissue, Anthony Atala, TEDTalks, streaming video

Anthony Atala's state-of-the-art lab grows human organs -- from muscles to blood vessels to bladders, and more. At TEDMED, he shows footage of his bio-engineers working with some of its sci-fi gizmos, including an oven-like bioreactor (preheat to 98.6 F) and a machine that "prints" human tissue.

TEDTalks is a daily video podcast of the best talks and performances from the TED Conference, where the world's leading thinkers and doers give the talk of their lives in 18 minutes. Featured speakers have included Al Gore on climate change, Philippe Starck on design, Jill Bolte Taylor on observing her own stroke, Nicholas Negroponte on One Laptop per Child, Jane Goodall on chimpanzees, Bill Gates on malaria and mosquitoes, Pattie Maes on the "Sixth Sense" wearable tech, and "Lost" producer JJ Abrams on the allure of mystery. TED stands for Technology, Entertainment, Design, and TEDTalks cover these topics as well as science, business, development and the arts.

grrlscientist Fri, 01/22/2010 - 00:59

Tags

Making new heart cells

edyong — Sun, 26 Apr 2009 11:00:09 +0000

Making new heart cells

It is literally very difficult to mend a broken heart. Despite its importance, the heart is notoriously bad at regenerating itself after injury. If it is damaged - say, by a heart attack - it replaces the lost muscle with scar tissue rather than fresh cells. That weakens it and increases the chance of heart failure later on in life. No wonder that heart disease is the western world's leading cause of death and illness.

If that picture seems bleak, two teams of scientists have some heartening news for you. The first has found that the heart does actually have the ability to renew its cells, albeit to a limited degree. And the second group has discovered a cocktail of proteins can nudge this process along, at least in mice.

Taking heart

The heart is made of an exclusive breed of cells called cardiomyocytes, whose synchronised contractions provide the heart with its beat. The cardiomyocytes develop from a more basic layer of cells called the mesoderm, which also gives rise to bones, cartilage and other tissues. Now, Jun Takeuchi and Benoit Bruneau from the Gladstone Institute of Cardiovascular Disease have found that a cocktail of three proteins - Gata4, Tbx5 and Baf60c - are enough to transform mesodermal cells into beating cardiomyocytes.

All three are needed for the job. Together, they managed to switch on the full gamut of genes needed to program the mesoderm of embryonic mice into heart cells. When they were added, Takeuchi and Bruneau found signs of various proteins that are associated with developing embryonic hearts, even in parts of the mesoderm that would normally not turn into heart muscle. These out-of-place cells developed very quickly too, for they started beating before the mice's own heart cells did.

That's a massive achievement and one that's completely unprecedented for mammals. Other groups have tried to use protein combos to produce cardiomyocytes in other species, but with little success. In chicks, certain combinations switched on genes involved in heart development, but never went the whole way. In frogs or zebrafish, which have simpler hearts, two proteins were used to produce heart cells, but with just a one in ten success rate. Takeuchi and Bruneau managed to do the same in 9 out of 11 mouse embryos.

Gata4 and Tbx5 are unique to the heart and faulty versions of them are linked to heart disorders. Both proteins are "transcription factors", molecular executives that control and activate other genes. But they're useless without Baf60c, another protein exclusive to the heart and whose absence causes heart defects.

Baf60c's is a doorman that allows the two executive proteins to do their work. It repackages DNA to expose specific genes for activation. Takeuchi and Bruneau showed that only in its presence could Gata4 stick to the DNA of two important heart-related genes. Takeuchi and Bruneau thinks that focusing on Baf60c was the key to their breakthrough. Gata4 can kick-start the sequence of events that produces heart cells and Tbx5 finishes things off. But Baf60c - the doorman protein - is needed to allow the other two to do their job in the first place.

If all this sounds promising, there's a massive caveat. So far, the duo has only managed to produce new heart cells in mouse embryos, and only very young ones at that. There's no guarantee that the same proteins could be used to encourage the growth of new heart cells in adult mice, let alone humans. Nonetheless, it's a good start and will hopefully lead to more answers down the line.

I <3 regeneration

There's another reason to think that there's a future in trying to stimulate the production of new cells in adult hearts - the process actually happens naturally. Until now, scientists have been unsure about whether we're stuck with the same set of cardiomyocytes from birth, or whether we can produce new ones. During our lives, our hearts become 30-50 times heavier, but that's mostly because existing cells swell in size.

Studying the turnover of new cells in such unchanging tissues is a big challenge. And it's one that can't be solved by the traditional method of injecting mildly radioactive nucleic acids to see if they get included in freshly created DNA. In lieu of that, Olaf Bergmann from the Karolinska Institute relied on an unorthodox method - he relied on fallout from the Cold War's nuclear test to carbon-date heart cells.

These tests released huge concentrations of carbon-14 - a mildly radioactive form of carbon - into the atmosphere. These levels spiked to unprecedented heights, only to quickly fall away after the Test Ban Treaty of 1963. In the meantime, the spike of carbon-14 was converted into carbon dioxide. Some of it was taken up by plants and made its way up the food chain to people alive at the time. Any new cells that people created during this time would have DNA that was laced with high levels of carbon-14. These levels act as a date-stamp for the cell's birthday, reflecting the amount of carbon-14 in the air when it was born.

Bergmann found that levels of carbon-14 in the hearts of people born before the Cold War were much higher than expected for the time. These hearts clearly contained cells that were created during the Cold War, after their owners were born. On average, it seems that our hearts are younger than we are by about 6 years.

Bergmann found the same thing when he focused only on the cardiomyocytes, which only make up a small fraction of the heart's cells. He tracked them down by searching for proteins found only in these cells and carbon-dated the DNA inside them. Again, their carbon-14 levels showed that they had been produced several years after their owner was.

Heart specialists might point out that cardiomyocytes do produce new DNA during childhood, so that adult cells have two or more genome copies. But we know that this duplication stops at the age of 10, and at least three of the people in Bergmann's sample were older than that before the Cold War sent atmospheric carbon-14 levels skyrocketing. The only explanation for the unusually high carbon-14 levels in their cardiomyocytes is that they were new cells.

Although adult hearts clearly do renew themselves, it's still a very slow process. Bergmann calculated that we regenerate around 1% of our heart every year in our 20s, and just 0.45% in our 70s. Based on his data, Bergmann thinks it's unlikely that only a few cardiomyocytes are producing new cells rapidly while the rest sit around idle. Instead, there's probably an even chance that any one cell is exchanged for a new version. But with such a slow turnover, the majority of our cardiomyocytes will never be exchanged - at the age of 50, just over half of these cells have been with us from birth.

This natural renewal is clearly not enough to repair the damage caused by a heart attack but at the very least, it suggests that there is a natural programme of repair that could be stimulated by combos of drugs or proteins, like the one discovered by the first study. Bergmann's work indicated that a target exists, and Takeuchi and Bruneau have suggested a way of hitting it.

References:

Takeuchi, J., & Bruneau, B. (2009). Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors Nature DOI: 10.1038/nature08039
Bergmann, O., Bhardwaj, R., Bernard, S., Zdunek, S., Barnabe-Heider, F., Walsh, S., Zupicich, J., Alkass, K., Buchholz, B., Druid, H., Jovinge, S., & Frisen, J. (2009). Evidence for Cardiomyocyte Renewal in Humans Science, 324 (5923), 98-102 DOI: 10.1126/science.1164680

More on cell turnover:

Images: Cardiomyocytes by Dr. S. Girod, Anton Becker; all other images from Nature

Subscribe to the feed

edyong Sun, 04/26/2009 - 07:00

Tags

An interesting direction and ingenious method of tracking the new cells. I wonder why the heart is particularly slow at regenerating or is that typical of most mammalian organs?

Nice post, dude!

Lilian - the heart's limited regeneration is most certainly not typical of mammalian organs. The cells of your skin, intestinal lining and blood, as three examples, renew themselves regularly. And the liver has astounding regenerative potential - it can regrow from a quarter of its original size.

A new discovery has been found to repair tissue damage caused by cardiac arrests. The scientists have experimented NRG1 on rats and it enhanced the general functioning of the heart. Though it is still unclear as to whether NRG1 is directly responsible for the cell renewal process, but the study has revealed that it can augment the regeneration process.

Great article! I believe the future of myocardial infarction repair will lie in our ability to activate stem cells and home them to the heart for regeneration. Converting similar cells to the desired tissue may present a problem in their downstream function in vivo. Regenerative medicine may have a more beneficial outcome.