Shark Bites No Match For Dolphins' Powers Of Healing

by Maureen Langlois

from http://www.npr.org/

 

Enlarge Courtesy of Dr. Michael Zasloff

  Nari, a dolphin bitten by a shark in February 2009, was almost completely healed one month later.

Courtesy of Dr. Michael Zasloff

 

Nari, a dolphin bitten by a shark in February 2009, was almost completely healed one month later.

Dr. Michael Zasloff, a surgeon and researcher at Georgetown University, is famous for discovering compounds in the skin of frogs and sharks that can fight disease in humans.

Now, he's tapping another animal to mine the secrets of its immune system. It turns out dolphins have a remarkable ability to heal quickly—and seemingly painlessly—from severe shark bites. Zasloff hopes that learning how dolphins resist infection and use stem cells to rebuild missing tissue will provide some insight into how to help injured humans.

To do this research, Zasloff reviewed the "clinical histories" of a few dolphins who recently succumbed to shark bites. He also interviewed all the dolphin experts he could find. His results appeared in a letter in the online version of the Journal of Investigative Dermatology.
  Shots caught up with Zasloff last week to learn more about his adventures in dolphin biology.
Q: OK, so imagine a human and a dolphin both being bitten by a shark. How would the healing process differ between the two?

Well, the dolphin wouldn't hemorrhage...or have any infection, which is miraculous. And despite having sustained massive tissue injury, within about month the animal will restore its normal body contour. There'll be some surface markings, but a chunk of tissue maybe the size of a football will have been restored with essentially no deformity.

And what is equally amazing is that handlers who know these animals will tell you that they observe absolutely no indications in the animal's behavior that it's in pain.

Q: And the human?
Even if it was a tiny bite, we would die of sepsis, or infection, within three or four days if we weren't given antibiotics because sharks have a lot of dangerous bacteria in their teeth. Then we'd have to make sure all the [infected tissue] was removed. If we were lucky and got it all, we'd still have this massive hole, which you may or may not be able to fill.

Q: Why are dolphins so good at healing?
Dolphin blubber makes compounds like organohalogens that act as natural antibiotics and keep the tissue from getting infected.


The next mystery is the recovery of contour [of the body]. When the animal restores its wound, it regenerates the complex structure of blubber. It doesn't create a scar; it produces a sort of patch that ultimately is woven back into the surrounding tissue.

What is exciting is that there must be great numbers of stem cells [involved], and by looking at these stem cells, we would probably be able to identify what they are and possibly even the hormones or proteins that are involved in their expansion. And if we looked for comparable cells in man, these might be the very cells that we would want to use to promote healing of complex wounds in us.

Q: So what are the next steps for research?
Identification of the antimicrobial agents, which have to be in those tissues. All you'd have to do is take some dolphin blubber, extract it, and start looking for stuff that would kill bacteria.

And with the pain issue, it's the same thing. You would take the blubber or the regenerating tissue, you'd isolate stuff—purified components or crude—and you'd administer it to mice. And lo and behold, you may find, in the regenerating tissue or the decomposing blubber, the long-sought natural morphine that we've been looking for.

Q: You've gone through the process of drug development with some of the compounds you've found in the tissue of other animals—frogs, for instance. How long before we see dolphin-inspired therapies?
I wish I could work on this, but I don't have access to dolphins. So I'm just putting this out there for other researchers to see. Once you appreciate that this is kind of a miracle, it isn't terribly hard to come up with ideas [for how to do the research]. The hardest part is to realize that there's a miracle in your midst.

Scientists grow 'embryonic eye' in test tube

From: http://www.telegraph.co.uk/

Eye transplants to cure blindness have taken a step closer after scientists managed to 'grow' a retina in the laboratory for the first time.

Cultured stem cells spontaneously organise themselves into an optic cup 

By Richard Alleyne, 

Science Correspondent

Researchers were amazed when stem cells in a test tube spontaneously organised themselves into a complex structure that resembles the developing embryonic eye.

The surprising development could lead eventually to whole retinas being cultured and then transplanted, restoring sight in the blind and visually impaired.

The team from the Institute of Physical and Chemical Research in Japan, first cultivated embryonic stem cells in a test tube and then added proteins to trigger them into developing.

They hoped that they would form a recognisable organ but were still stunned when over 10 days they clustered together and began to grow the "optical cup" of a retina.

Tests showed that the cells were functioning normally and were capable of communicating with each other.

The research was done on mouse eyes, but there is no reason why a similar technique would not work on humans, said the experts.

They hope that within 10 years to be able to start clinical trials on retina implants.

"This is an absolutely stunning achievement," said Professor Robin Ali, an ophthalmologist at University College London.

"It is a landmark not just for the retina but for regenerative medicine as a whole."
More than a million people in Britain suffer from vision problems caused by a damaged or malfunctioning retinas.
The retina is the "business end" of the eye, where nerve cells convert light into electrical and chemical signals that are sent to the brain down the optic nerve.

If it is not working then the eye is useless.

Professor Yoshiki Sasai, lead author said: "What we've been able to do in this study is resolve a nearly century-old problem in embryology, by showing that retinal precursors have the inherent ability to give rise to the complex structure of the optic cup."

His team, who filmed the technique as it unfolded, grew floating clusters of the mouse cells in a special tissue culture in the laboratory that had previously been successfully used to make a variety of brain cells.

By adding particular proteins they were able to get the cells to build a three dimensional layered structure reminiscent of the optic cup within 10 days.

The retinal neurons ultimately organised into a six-layer structure closely resembling that of a retina shortly after birth.

This could eventually lead to treatments aimed at repairing the eyes of people with conditions that limit or destroy their sight.

Potential applications include regenerative medicine approaches to the treatment of progressive genetic disorders such as retinitis pigmentosa.

Prof Ali, who reviewed the research published in Nature, said: "For the first time, we see unfolding in real time the beautiful events that shape the early stages of mammalian eye development.

"But even more remarkable is that these are not recordings from live animals, but of self-organising 3-D cultures of embryonic stem cells."

Chemical found which 'makes bone marrow repair skin'

From: http://www.bbc.co.uk/

 

Skin grafts trigger repair by bone marrow cells

The chemical which summons stem cells from bone marrow to the site of a wound has been discovered by scientists in the UK and Japan.

The study, published in Proceedings of the National Academy of Sciences, identified the distress signal - HMGB1.

The authors believe it can be used to put "a megaphone in the system" to improve the treatment of injuries such as burns and leg ulcers.

Another UK expert said the research had potential.

Bone marrow was thought to play a role in repairing damaged skin, but the exact process was unknown.
Scientists at Osaka University and King's College London gave mice bone marrow cells that glow green - which can be tracked while moving round the body.

They then wounded the mice and some were given skin grafts.

Megaphone medicine
 
In mice without grafts, very few stem cells travelled to the wound. Those with grafts had many stem cells travelling to the wound.

Professor John McGrath, from King's College London, says grafted skin tissue has no blood vessels and therefore no oxygen. He says this environment leads to the release of HMGB1 - or what he called a 'Save Our Skin signal' - which results in stem cells moving to the wound.

He said: "It could have a very big impact on regenerative medicine for treating people with rare genetic illnesses and more common problems such as burns and ulcers.

"It could potentially revolutionise the management of wound healing."

He envisaged treatments in which a drug similar to HMGB1 would be injected near to a wound.
He said: "It would be like putting a megaphone in the system" bringing stem cells to the injury.

Researchers in Osaka are developing a drug to mimic HMGB1. They hope to begin animal testing by the end of the year and human clinical trials shortly afterwards.

Phil Stephens, professor of Cell Biology at Cardiff University, said: "I think it has potentially big clinical implications, but the key is potential if you can control it. You can't just chuck it on, you need the right amounts at the right time."

"Identifying the mechanism is a really important first step."

Freeing Up Stem Cell Research

Cell boom: Shown here is a colony of embryonic stem cells. Credit: NIH

Three years ago, when Rene Rejo Pera was setting up a new lab at the University of California, San Francisco (UCSF), she had to make sure she had two of everything: one microscope for her federally funded lab, for example, and one for a privately funded replica next door. Because of funding restrictions on stem-cell research ordered by President George W. Bush in 2001, this was a redundant scenario played out in labs across the country. The edict specifically limited federal funding for embryonic stem-cell research to a small number of cell lines already in existence, leaving scientists who wanted to conduct cutting-edge research in this area scrambling for private money.

Scientists are now looking forward to an end of that edict. President Barack Obama promised during his campaign to overturn the order, and most expect the action to happen soon. "The imminent change in policy will quite literally allow us to take down these walls and integrate the laboratories in a way that will make the work move much more efficiently," says Arnold Kriegstein, director of the Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

The new policy is expected to mean that scientists will have unfettered access to newer, better embryonic stem cells, which will speed the pace of research. Even without funding restrictions, however, scientists receiving government grants could not use that money to generate new lines, which requires the destruction of an embryo. Kriegstein and others hope that the change will bring a new sense of legitimacy to an often embattled field, as well as return a leadership role to the National Institutes of Health (NIH), the nation's premier biomedical funding agency, in one of the most promising areas of biomedical research. Much of the research has shifted to institutes funded by state initiatives, such as the California Institute for Regenerative Medicine, or by private donors. In addition to limiting funding, "the other reality of [the Bush] policy is all the negative publicity it has created," says Tim Kamp, codirector of the Stem Cell and Regenerative Medicine Center at the University of Wisconsin. "Frankly, I think it did greater damage than funding restrictions, [in] that it scared many researchers away."

Despite the restrictions, U.S. scientists have employed embryonic stem cells for a broad range of research. Because the cells can develop into any tissue type, scientists are coming up with ways to prod them to differentiate into brain cells, heart cells, and other cell types, both to better understand the diseases that strike these tissues and to potentially create replacement tissue for therapies. But much of the most promising research has moved overseas.

Once the restriction is lifted, labs funded by federal dollars will be allowed to use most of the estimated 600 stem-cell lines that have been created around the globe. Researchers broadly agree that the newer lines, which were derived using more refined methods, are superior to the older ones. Using only the old lines is like "being required to use Microsoft Word 1998," says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute, in La Jolla, CA.

In addition, the earlier lines were derived using animal products, making them largely unfit for therapeutic use. "There are hundreds of embryonic stem-cell lines out there that have been made under the best conditions, and some of them are patient ready," says John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania, in Philadelphia. "They have greater utility, performance, and safety than [the Bush-approved] lines."

Scientists will also be able to study cell lines that are genetically encoded for specific diseases--perhaps one of the most promising near-term uses of embryonic stem cells. (None of the Bush-approved lines have these qualities.) "One of the clear opportunities that has not been available are lines generated from embryos that carry mutations for Huntington's disease, amyotrophic lateral sclerosis (ALS), and cystic fibrosis," says Story Landis, director of the National Institute for Neurological Disorders and Stroke, in Bethesda, MD, and chair of the NIH's Stem Cell Task Force. These cells provide unprecedented access to the molecular processes underlying disease; they can be prodded to develop into the cell type affected in a specific disease, such as motor neurons in ALS, so that scientists can watch the disease unfold at a cellular level. These cells can also be used to screen new drugs.

Scientists and policy makers are still guessing as to when and how President Obama will reverse the restrictions--whether he will issue an executive order, or let Congress decide the matter. But according to White House press reports last week, the president promised the former. Prior to Obama's presidency, Congress twice passed a bill reversing the restrictions, the Stem Cell Research Enhancement Act, which Bush twice vetoed.

It's not yet clear how quickly the field will rebound from the funding limits. Many scientists were discouraged from studying embryonic stem cells during the past eight years because they couldn't secure private funds, or because they or their universities did not want to deal with the extensive accounting required. "The effect of the restrictions was to create a few centers going forward, like mine and like Harvard, Stanford, and UCSF, which had access to private and state money," says Loring. "Now there will be more room for people to get involved, but they'll be eight years behind."

The field has changed dramatically since President Bush's edict, especially in the past two years, which may make new funding freedom less significant. A newly developed technique to create stem cells--called induced pluripotent stem (iPS) cell reprogramming--does not require the destruction of human embryos, and scientists hesitant to take on embryonic stem cells have been flocking to the new approach in droves.

Researchers have been able to do many of the same experiments with these iPS cells as they have with embryonic stem cells. However, they caution that these cells have not been shown to carry all the power of embryonic cells--for example, they cannot differentiate into as many cell types. "It's very important that labs be able to do experiments with both kinds of cells side by side," says Kriegstein. "Relaxing presidential policies will make this much easier to accomplish."

One area of research that won't change with removal of the restrictions is therapeutic cloning. In therapeutic cloning (also called somatic cell nuclear transfer), scientists transplant DNA from an adult skin cell into an egg that has had its DNA removed. Unknown factors in the egg reprogram the adult DNA to resemble embryonic DNA, and, in theory, the cell begins to develop like a normal embryo. Scientists would like to create stem cells from cloned human embryos, both for research and potentially for therapy: the cells would be genetically matched to their human donors and thus could be transplanted without fear of rejection. But no one has yet accomplished this with human cells and eggs. Research that involves destruction of human embryos, which includes both cloning and derivation of new stem-cell lines, is prohibited from federal funding under the Dickey Amendment, a rider to the appropriations bills that have been passed in Congress over the past several years.

By Emily Singer