121 replies to this topic

[kevin]

Link: http://www.eurekaler...i-scc060104.php

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Public release date: 1-Jun-2004
Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions

Stem cells can convert to liver tissue, help restore damaged organ
Bone marrow stem cells, when exposed to damaged liver tissue, can quickly convert into healthy liver cells and help repair the damaged organ, according to new research from the Johns Hopkins Kimmel Cancer Center.

In mouse-tissue cultures, scientists found that stem cells, in the presence of cells from damaged liver tissue, developed into liver cells in as little as seven hours. They also observed that stem cells transplanted into mice with liver injuries helped restore liver function within two to seven days. The work was published in the June 1 issue of the journal Nature Cell Biology.

Bone marrow stem cells, also known as hematopoietic stem cells, have the ability to differentiate and develop into all other blood and marrow cells. There has been debate among the scientific community over whether these cells also can differentiate into other tissue types such as the liver, says Saul J. Sharkis, Ph.D., senior author of the study and a professor of oncology at the Johns Hopkins Kimmel Cancer Center. Some studies suggest that the bone marrow cells fuse with other types of cells, taking on those cells' properties. But in this study, the researchers found, through highly thorough analysis with a microscope and other tests, that the cells did not fuse, suggesting that "microenvironmental" cues from existing liver cells caused them to convert.

"The hematopoietic stem cells were capable of taking on many characteristics of liver cell types, including specific gene and/or protein expression as well as typical function," Sharkis says. "These events occurred rapidly after injury exposure and restored liver abnormalities, indicating that the cells converted."

This type of stem cell technique could eventually be used to treat chronic diseases such as diabetes, cirrhosis of the liver, heart disease and cancer, he says. He cautions that many more studies must be completed before the stem cell therapy can be tested in humans.

For the study, Sharkis and colleagues cultured bone marrow stem cells together with either normal or damaged liver tissue in tissue culture dishes. Liver tissue was taken from mice that had been exposed to liver-damaging drugs. The two cell types were separated by a thin, permeable wall. Researchers performed several tests looking for expression of liver proteins.

In as little as seven or eight hours after culture with the injured liver tissue, some of the stem cells expressed the typical proteins present in liver cells cytokeratin 18 or albumin. Two days after culture, nearly 3 percent of all stem cells expressed these proteins. The researchers also observed the expression of many other proteins and products normally manufactured by liver cells in their earliest stages -- all detected within eight to 48 hours of culture.

The team then used a sensitive microscope test to examine the sex chromosomes of the cells, as the stem cells were taken from male mice and the liver tissue was taken from female mice. They identified some stem cells of male donor origin with four sex chromosomes typical of liver cells but not stem cells, indicating that the stem cells themselves physically had started to change and did not fuse with the liver cells.

Finally, the team transplanted the stem cells into injured livers in female mice and studied the amount of conversion at two and seven days following the transplant. More converted cells were observed at seven days versus two days, suggesting that the cells remained viable and continued dividing or converting. The liver functions of mice receiving the stem cells recovered as early as two days after transplant.

Sharkis' continuing studies will try to identify the environmental cues responsible for cells' conversion, and examine the ability of stem cells to repair other organs.

The study was funded by the National Heart, Lung and Blood Institute, the Ludwig Foundation and Hopkins' Institute for Cellular Engineering. Co-authors were Yoon-Young Jang M.D., Ph.D.; Michael I. Collector; Stephen B. Baylin, M.D.; and Anna Mae Diehl, M.D.


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Jang, Yoon-Young et al, "Hematopoietic Stem Cells Convert Into Liver Cells Within Days Without Fusion," Nature Cell Biology, June 1, 2004.

Links:

Johns Hopkins Kimmel Cancer Center
http://www.hopkinski...ncercenter.org/

Nature Cell Biology
http://www.nature.com/ncb/

[randolfe]

Kevin, the pace and promise of all this research literally takes my breath away.

However, I find this statement from the "fat-into-stem-cells" article to be extremely depressing:

"As a source of cells for treatment, adipose tissue is not only limitless, it does not carry the potentially charged ethical or political concerns as other stem cell sources, the researchers said.

"This is a big step to take undifferentiated cells that haven't committed to a particular future and redirect them to develop down a different path," said Duke surgeon Henry Rice, M.D., senior member of the research team. "Results such as these challenge the traditional dogma that once cells become a certain type of tissue they are locked into that destiny"

This lead-weight drag on research because an embryo is involved shows that for all our technical abilities, we are not far removed from the ancient worshippers of the Sun. I appreciate that each of us was once a two cell embryo but this continuing interference with research by those who insist on equating an embryo as equivalent to an existing human life is nothing less than "embryo worship". Given a choice between the two, I'd rather worship the Sun. Given infinite choice, I would choose to "worship" nothing--to just embrace science and pursue the understanding and mastering of life.

[kevin]

Kevin, the pace and promise of all this research literally takes my breath away.

However, I find this statement from the "fat-into-stem-cells" article to be extremely depressing:

"As a source of cells for treatment, adipose tissue is not only limitless, it does not carry the potentially charged ethical or political concerns as other stem cell sources, the researchers said.

Personally, I don't care if stem cell therapies capable of rejuventating the body arise from adult stem cells instead of embryonic stem cells. I doubt very much that the 'miracle of life' will ever be seen as a totally mechanical interplay of physical forces tantamount to booting up an operating system and bringing a computer online... or wait.. if it was an AI.. Michael might say that pulling the plug or interfering with that process might be interfering with *its* rights..

Nope.. I think we will have to acknowledge that the 'mystery' of life will likely remain such for the forseeable future and in being a mystery will be subject to divine interpretation.

That being said.. I think the success with ASC's and their clinical use, will have a profound effect on shifting attitudes to thinking that we ARE made up of replaceable parts, especially neuronal regeneration of Alzheimer afflicted individuals, and this will lead to the further eroding of the 'fully formed' soul at fertilization concept which seems to run through most of the objections to the use of ESC's.

Anytime I get into a discussion about ESC's with one of religious bent, I ask them what we are supposed to do with the hundreds of thousands of embryos created through IVF? Their response is usually they should never have been created in the first place.. which doesn't answer the question so I usually have to pose it again, asking them that if Jesus, who healed the sick on the Sabbath in direct defiance of the law, had to make the decision as to the fate of these embryos, what would he do?. Would he throw out the embryo, murdering it, leave it frozen in a Dewar until it was no longer viable, imprisonment and murder, or would he go against the pharisees of modern times to use it for the opportunity to heal the afflictions of millions. Most of the time the person is left stuttering and I don't get an answer.. because the truth is instinctive.. a suffering fully formed human with a history and future is more valuable than an embryo destined for the drain... and that is the same conclusion the person that people hold Jesus up to be would come to in my mind.

[kevin]

Here's a post Aubrey placed on the sci.life-extension newsgroup. A wonderful development that he is now putting his substantial drive to promoting regeneration!

Rejuvenation Research: First Issue is Out

From: Aubrey de Grey (ag24@mole.bio.cam.ac.uk)
Subject: Rejuvenation Research: first issue is out
This is the only article in this thread 
View: Original Format
Newsgroups: sci.life-extension
Date: 2004-06-02 11:33:50 PST


The first issue of Rejuvenation Research has just been published.

Rejuvenation Research is a relaunch of the Journal of Anti-Aging
Medicine, coinciding with my taking over as Editor-in-Chief from
Michael Fossel.  It will publish the highest-quality research in
all areas of biology relevant to expediting the development of a
real cure for human aging, including stem cell therapy, tissue
engineering, gene therapy and many other areas not conventionally
covered by biogerontology journals, as well as areas that are
more conventionally classified as biogerontology.  It will also
feature extensive analysis of the social context of such work.

A fuller description of the aims and scope of RR is contained in
the editorial to the first issue, which I thank the publishers,
Mary Ann Liebert, Inc. of New York, for allowing me to post at my
website:

   http://www.gen.cam.a...ens/firsted.pdf

The quality that can be expected of this journal is best shown by
the calibre of its editorial board, which consists of established
leaders in all relevant areas.  See below for a link to the list
of board members.

I hope you will consider either taking out a personal subscription
or, if you are a member of an academic institution, recommending
them to take out an institutional subscription.  Or both, of course!
Subscribers can access the journal online shortly after publication;
I am told that issue 1 will be online by the end of this week.

Relevant URLs:

Journal home page (including subscriptions):
   http://www.liebertpu...ej/default1.asp

Editorial Board:
   http://www.liebertpu...oard.asp?id=127

Table of Contents:
   http://www.liebertpu.../Toc.asp?id=127

Instructions for Authors:
   http://www.liebertpu...ipts.asp?id=127

Any queries or comments regarding RR are of course welcome.

Aubrey de Grey

[kevin]

Link: http://www.eurekaler...t-mtj060904.php

It's becoming increasingly obvious that stem cell differentiation is perhaps more dependent on physical cues from the surrounding environment rather than on signalling of molecules. ie. Crowding stem cells' personal space directs their future Which is why I am so enthused about the following post where miniaturization and the 'microarraying' of potential scaffolding materials to test their effect on stem cell differentiation is going to lead to rapid characterization of potential scaffold candidates.

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Public release date: 13-Jun-2004
Contact: Elizabeth Thomson, MIT News Office
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology

MIT technology jump-starts human embryonic stem cell work

CAMBRIDGE, Mass.--An MIT team has developed new technology that could jump-start scientists' ability to create specific cell types from human embryonic stem cells, a feat with implications for developing replacement organs and a variety of other tissue engineering applications.

The scientists have already identified a simple method for producing substantially pure populations of epithelial-like cells from human embryonic stem cells. Epithelial cells could be useful in making synthetic skin.

Human embryonic stem cells (hES) have the potential to differentiate into a variety of specialized cells, but coaxing them to do so is difficult. Several factors are known to influence their behavior. One of them is the material the cells grow upon outside the body, which is the focus of the current work.

"Until now there has been no quick, easy way to assess how a given material will affect cell behavior," said Robert Langer, the Germeshausen Professor of Chemical and Biomedical Engineering. Langer is the senior author of a paper on the work that will appear in the June 13 online issue of Nature Biotechnology.

The new technique is not only fast; it also allows scientists to test hundreds to thousands of different materials at the same time. The trick? "We miniaturize the process," said Daniel G. Anderson, first author of the paper and a research associate in the Department of Chemical Engineering. Anderson and Langer are coauthors with Shulamit Levenberg, also a chemical engineering research associate.

The team developed robotic technology to deposit more than 1,700 spots of biomaterial (roughly 500 different materials in triplicate) on a glass slide measuring only 25 millimeters wide by 75 long. Twenty such slides, or microarrays, can be made in a single day. Exposure to ultraviolet light polymerizes the biomaterials, making each spot rigid and thus making the microarray ready for "seeding" with hES or other cells. (In the current work, the team seeded some arrays with hES and some with embryonic muscle cells.)

Each seeded microarray can then be placed in a different solution, including such things as growth factors, to incubate. "We can simultaneously process several microarrays under a variety of conditions," Anderson said.

Another plus: the microarrays work with a minimal number of cells, growth factors and other media. "That's especially important for human embryonic stem cells because the cells are hard to grow, and the media necessary for their growth are expensive," Anderson said. Many of the media related to testing the cells, such as antibodies, are also expensive.

In the current work, the scientists used an initial screening to find especially promising biomaterials for the differentiation of hES into epithelial cells. Additional experiments identified "a host of unexpected materials effects that offer new levels of control over hES cell behavior," the team writes, demonstrating the power of quick, easy screenings.


###
This work was funded by the National Science Foundation and the National Institutes of Health.

[randolfe]

These latest findings about scaffolding stem cells and their ability to get the proper signals for differentiation from surrounding tissue just underscores how much could be accomplished if we had more governmental funding for this type of research.

I think that this idea of replacing worn out body parts one by one as needed has an essential flaw. This is somewhat akin to "achieving immortality" on an installment plan.

I would not be surprised if all the amazing accomplishments of stem cell research are swept away at some future time by the discovery of a mechanism which reverses (or simply stops) aging throughout the body.

I would see that as a three step process: (1) greatly slow the agining process; (2) totally stop the aging process; (3) reverse the aging process.

Imagine a life in which one simply grew younger each year. Birthdays would really be causes for celebration. Now, they are simply road markers along the road to the grave.

One wonders at what age experienced adults would choose to live "eternally". Would some choose age eighteen, others twenty-five, others thirty-five? Would some choose to "swing back and forth between certain ages"?

This seems to be an interesting idea for some positive science fiction writing. These are the kind of provocative ideas that cause people to think of really interesting possibilities and become excited about the promise of science and the possibilities of regeneration.

[kevin]

Link: http://www.eurekaler...o-ngk062104.php

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Public release date: 21-Jun-2004

Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine

Newly grown kidneys can sustain life in rats
Researchers take critical first step toward using animal tissue transplants to treat kidney failure
St. Louis, June 21, 2004 -- Growing new organs to take the place of damaged or diseased ones is moving from science fiction to reality, according to researchers at Washington University School of Medicine in St. Louis.

Scientists have previously shown that embryonic tissue transplants can be used to grow new kidneys inside rats. In their latest study, though, they put the new kidneys to an unprecedented and critical test, removing the rat's original kidneys and placing the new kidneys in position to take over for them. The new kidneys were able to successfully sustain the rats for a short time.

"We want to figure out how to grow new kidneys in humans, and this is a very important first step," says Marc R. Hammerman, M.D., the Chromalloy Professor of Renal Diseases and leader of the study. "These rats lived seven to eight days after their original kidneys were removed, long enough for us to know that their new kidneys worked."

The study will appear in the July/August issue of Organogenesis, a new scientific journal. It is also available online.

Hammerman is a leader in the burgeoning field of organogenesis, which focuses on growing organs from stem cells and other embryonic cell clusters known as organ primordia. Unlike stem cells, organ primordia cannot develop into any cell type--they are locked into becoming a particular cell type or one of a set of cell types that make up an organ.

"Growing a kidney is like trying to construct an airplane--you can't just make a single part like a propeller, you have to build several different parts and systems and get them all working together properly," Hammerman explains. "Fortunately, kidney primordia already know how to grow different parts and self-assemble into a kidney--we just have to give them the right cues and a little assistance at various points."

For the study, Hammerman and coauthor Sharon Rogers, research instructor in medicine, gave renal primordia transplants to 5- and 6-week-old rats. Prior to insertion, scientists soaked the transplant tissue in a solution that included several human growth factors, proteins and hormones. One of the rats' original kidneys was removed at the same time.

Three weeks after the transplant, researchers connected the new kidneys to the bladder and administered a second dose of growth factors.

Approximately five months after the transplants, scientists removed the remaining original kidney in control and experimental rats. To help resolve uncertainty about which kidney functions are critical to sustaining life, scientists cut the connections between the bladder and the new kidneys in a subset of the experimental rats.

Rats with no new kidneys lived for two to three days, and rats whose new kidneys were disconnected from their bladders lived no longer. However, the rats with new kidneys connected to their bladders lived seven to eight days.

"This tells us that the urine-producing functions of the kidney are key to preservation of life," says Rogers.

"Seven to eight days may not seem like a long time," adds Hammerman. "However, what we have done is akin to building the first airplane and showing that it can fly, if only for a few minutes. It's just as revolutionary."

In this study and in other previous research, Hammerman and Rogers have established that the newly grown kidneys can perform many essential renal functions.

"For example, we've shown that they can excrete inulin, an inert sugar that we inject into a rat's bloodstream," Hammerman says. "This demonstrates that the kidneys are filtering the blood."

When scientists injected the rats with another compound known as p-aminohippurate, the kidney began to secrete it into the urine.

In addition to excretion and filtration, the new kidney also has to reabsorb salts, water and key nutrients. The researchers have shown that the new kidneys can reabsorb both water and the nutrient phosphorus.

Hammerman, who is director of the Renal Division at the school's affiliate Barnes-Jewish Hospital, hopes to use animal-to-human transplants, known as xenotransplants, as a solution for chronic organ donation shortages.

"Every year, approximately 10,000 kidneys become available for transplant into patients with end-stage kidney disease," Hammerman says. "But the waiting lists for kidney transplants can run as high as 100,000 individuals, and most patients die of the disease before an organ becomes available."

Kidney function in pigs is similar to that in humans, and Hammerman's eventual goal is to use embryonic pig tissue transplants to help renal failure patients live longer.

Working with embryonic tissues that grow into organs inside the patient lets Hammerman avoid hyperacute and acute vascular rejection, two immune system responses that can destroy xenotransplants. In both of these responses, the body's immune system recognizes the blood vessels of transplanted tissue as foreign and attacks them.

"Those two types of rejection have so far made it impossible to xenotransplant fully grown kidneys," Hammerman explains. "However, we can avoid this by transplanting embryonic kidneys before blood vessels develop."

The primordia are small enough that survival can be maintained after transplantation through diffusion of oxygen and nutrients. The transplanted cells attract the growth of new blood vessels from the host as they grow into a mature organ.

Hammerman notes that recipients of embryonic xenotransplants will still have to take immune suppression drugs to prevent acute rejection, a third type of immune response that directly attacks transplanted tissues. But recipients of human kidney transplants also must take immune suppression drugs.

Hammerman and Rogers published their first report on growing kidneys in 1998. They are currently working to perfect pig-to-rat xenotransplantation of kidney primordia. If they can extend life in pig-to-rat transplants, the next steps are pig-to-primate and then pig-to-human transplants.

"Therapies based on growing new organs will be part of mainstream medical practice by the middle of the 21st century," predicts Hammerman, who is also working to develop approaches for growing a new pancreas as a treatment for diabetes.


###
Rogers SA, Hammerman MR. Prolongation of life in anephric rats following de novo renal organogenesis. Organogenesis, July/August 2004.

Funding from the National Institutes of Health.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

[kevin]

Link: http://www.eurekaler...m-eso090704.php

---

Public release date: 7-Sep-2004

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania Medical Center

Extreme stretch-growth of axons
Pushing neurons' physiological limits provides researchers with new ways to repair nerve damage

Axon tracts stretch-grown to 5 cm. Axon tracts (middle) bridge two populations of neurons (top and bottom). Credit: B. Pfister et al./The Journal of Neuroscience 24(36):7978-83. Reproduced with permission from The Journal of Neuroscience, c 2004 by the Society for Neuroscience. Click here for a high resolution photograph.

(Philadelphia, PA) – Sometimes it is the extremes that point the way forward. Researchers at the University of Pennsylvania School of Medicine have induced nerve fibers – or axons – to grow at rates and lengths far exceeding what has been previously observed. To mimic extreme examples in nature and learn more about neuronal physiology, they have mechanically stretched axons at rates of eight millimeters per day, reaching lengths of up to ten centimeters without breaking. This new work has implications for spinal cord and nerve-damage therapy, since longer implantable axons are necessary for this type of repair.

In the present study, the team, led by Douglas H. Smith, MD, Professor of Neurosurgery and Director of the Center for Brain Injury and Repair, placed neurons from rat dorsal root ganglia (clusters of nerves just outside the spinal cord) on nutrient- filled plastic plates. Axons sprouted from the neurons on each plate and connected with neurons on the other plate. The plates were then slowly pulled apart over a series of days, aided by a precise computer-controlled motor system. "By rapid and continuous stretching, we end up with huge bundles of axons that are visible to the eye," says Smith. The axons started at an invisible 100 microns and have been stretched to 10 centimeters in less than two weeks. Smith and colleagues report their findings in the cover story of the September 8, 2004 issue of the Journal of Neuroscience.

"This type of stretch growth of axons is really a new perspective," says Smith. Despite the extreme growth in length, the axons substantially increased in diameter as well. Using electron microscopy, they confirmed this growth by identifying a fully formed internal skeleton and a full complement of cellular structures called organelles in the stretched axons. "Surprisingly, the axon appears to be invigorated by this extreme growth," says Smith. "It doesn't disconnect, but forms a completely normal-appearing internal structure."

These extreme rates of growth are not consistent with the current understanding of the limitations of axon growth. "Proteins necessary to sustain this growth are somehow correctly brought to sites along the axon faster than conceivable rates of transport," notes Smith. The team suggests two possible mechanisms to explain this: increasing transport to a very fast rate or making the necessary proteins at the site, proximal to the growing axons. Smith believes that this form of growth commonly occurs in nature. "For example, it can be inferred that axons in a blue whale's spine grow more than three centimeters a day and in a giraffe's neck at two centimeters a day at peak growth."

The team also found that they had to condition the axons to grow in an extreme way. "Although they can handle enormous growth, you can't just spring it on them," explains Bryan Pfister, PhD a post-doctoral fellow in Smith's lab and coauthor of the study. "If we ramp up the stretch rate too fast, the axons will snap." From this the team surmises that in nature animals must grow at a metered pace, which allows for constant feedback and conditioning.

It has been well established that axons initially grow out from neurons and follow a chemical stimulus to connect with another neuron. However, once the axon has reached its target a relatively unknown form of stretch-growth must ensue as the animal grows. Mechanical changes in the growing brain, spine, and other bones are the starting point for natural stretch-growth in axons. "We know that it's not tension on the neuron itself, but tension on the axon," says Smith. "It's deformation, a pulling on the axon." At this point, it is unclear what receptors and cell signaling pathways are involved to get the process started, but from this and previous studies the investigators do report that the signal is from a mechanical stimulus along the length of the axon as opposed to a chemical stimulus. "The stretch is coming from the whole body growing," explains Smith. "For example, the growing spine bones in the whale likely exert mechanical forces on the axons in the spinal cord."

The researchers conclude that this is a genetic program for growth that has been conserved throughout animal species, but just hasn't been studied in depth. By revealing the mechanisms of extreme-stretch growth, the team is currently applying this knowledge to develop nerve constructs to repair nerve and spinal cord damage. "To find that tension is actually good for your nerves for both growth and repair may not be such a long stretch," says Smith.


###
Penn colleagues on the paper are: Akira Iwata and David F. Meany. This research was funded by the National Institutes of Health.

For a copy of the paper, please contact Dawn McCoy or Elissa Petruzzi at the Society for Neuroscience at 202-462-6688. For permission to use images within the paper, please contact Lionel Megino at the Society at lionel@sfn.org.

This release can also be found at: www.uphs.upenn.edu/news.

[kevin]

Link: http://dbs.cordis.lu...CALLER=FP6_PROJ

It seems that France is not sitting on its heels when it comes to regenerative stem cell therapy. This looks like a pretty big push to characterize mesenchymal stem cells.

---

Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side

The objective of this Integrated Project Genostem is to establish an European international scientific leadership for stem cell regenerative medicine in the field of connective tissue disorders. Autologous adult Mesenchymal Stem Cells (MSCs) are optimal candidates to serve as the building blocks for the engineering of connective tissues being multipotential stem cells that give rise to osteoblasts, chondrocytes and tenocytes, muscle cells and adipocytes. Genostem will compare different tissue sources of MSCs and isolate subsets in order to obtain undifferentiated MSCs, committed MSCs at early stage of differentiation, progeny blocked at specific differentiation stage and fully differentiated progeny.

Genostem will study the complete MSC gene product repertoire using genomic and proteomic analysis that should provide with the molecules and pathways potentially operative for the maintenance and differentiation of stem cells. Genostem will develop innovative technologies to generate biodegradable matrices, scaffolds and microcarriers that bind pharmacologically active proteins and allow their delivery in a controlled way; these biomaterials will allow to engineer MSCs such as to obtain optimal repair of the target injured tissue. Genostem will improve methods for gene transfer using original virus or non viral delivery systems in order to carry out gain (gene transfer) and loss (siRNA transfer) of function studies. Genostem will develop transplantation models of MSCs mimicking human pathological processes operative in bone cartilage and tendon diseases. The final goal is to develop clinical trials using MSCs, in bone, cartilage and tendon disorders, in partnership with SMEs and regulatory bodies for the scale up of safe procedures, taking advantage of the experience already acquired by one of the partner in clinical trials using cultured muscle cells.

Home Page: http://www.genostem.org

[kevin]

Link: http://www.discover....bald-men-mouse/

---

Bald Men: This Mouse is For You
By Aaron J. Sender
DISCOVER Vol. 26 No. 01 | January 2005 | Biology & Medicine
Courtesy of Rockefeller University


A single stem cell produced the clump of hair growing on this bald mouse’s back, as well s the epidermis, follicles, and sebaceous glands that nurture the fur.

The cure for baldness may be imminent. A Rockefeller University research team led by biologist Elaine Fuchs reported last September that they had coaxed adult stem cells to grow hair. When grafted onto bald mice, the cells produced not only furry tufts but stretches of skin complete with the oil-producing glands that help keep it supple as well. “Essentially, you’d put down a forest rather than plant tree by tree,” says Fuchs.

Earlier work hinted that skin follicles harbor stem cells kept in reserve to replace epidermal cells when they die. “The critical question was whether there really is a cell that can do it all—epidermis, hair, sebaceous glands,” says Fuchs. “And now we know that we really have a bona fide stem cell.” That means curing baldness could just be the beginning. “Maybe these stem cells could do other things,” says Fuchs. “Maybe they could make corneas for the treatment of blindness.”

The full potential of various stem cells found in adults is still unknown. “It’s just presumed that they have fewer capabilities than embryonic stem cells,” says Bill Lowry, a coauthor of the study. But, he adds, harvesting adult stem cells from skin has one clear benefit: “It’s such an easily accessible source.”

[kevin]

Link: http://www.massgener...05faustman.html

---

Spleen may be source of versatile stem cells
Cells have protein associated with embryonic development, limb regeneration
BOSTON - January 19, 2005 - A year ago, Massachusetts General Hospital (MGH) researchers discovered that the spleen might be a source of adult stem cells that could regenerate the insulin-producing islets of the pancreas. In a follow-up to that unexpected finding, members of the same team now report that these potential adult stem cells produce a protein previously believed to be present only during the embryonic development of mammals.

The finding both supports the existence of these splenic stem cells and also suggests they may be able to produce an even greater variety of tissues. The report appears in the January 19 issue of SAGE KE (http://sageke.sciencemag.org ), an online resource on the science of aging from the publishers of the journal Science.

"There may be a previously undiscovered pocket of primitive stem cells in the spleen that are important for healing several types of damage or injury," says Denise Faustman, MD, PhD, director of the MGH Immunobiology Laboratory and senior author of the SAGE KE report. "If so, these cells could have much broader therapeutic applications than suggested by our earlier work."

In 2001 Faustman's team found that a treatment designed to address the autoimmune reaction underlying type 1 diabetes actually cured the disease in diabetic mice. Late in 2003 they reported the mechanism behind the earlier discovery: cells from the spleens of donor mice - intended to train the diabetic animals' immune systems not to attack islet cells - were actually producing new islets. The result suggested that the adult spleen - previously regarded as playing a fairly minor role in regenerative medicine - might contain a population of potential islet stem cells.

In their pursuit of that finding, the MGH researchers investigated the possible presence of a protein called Hox11 in these cells. In mammals, Hox11 is a controller of key steps in embryonic development - including the formation of the spleen - but it was not known to be present in adults under normal circumstances. In some other animals, however, the protein has an intriguing function: when creatures like newts regenerate a lost limb or tail, production of Hox11 is radically increased.

As reported in their SAGE KE article, the MGH team did find that Hox11 was produced in the spleens of adult mice by the same cells that regenerated the islets in the earlier study. They also found that these cells did not produce a protein known to be associated with a cellular commitment to develop into a particular type of tissue. Without that commitment, the splenic cells may be able to differentiate into a wider variety of cells than can adult stem cells from bone marrow, which do not produce Hox11.

The researchers also note that the spleen develops from embryonic tissue that is known not only to generate precursors to many types of blood cells, a function shared by the bone marrow, but potentially to form such diverse organs as the small intestine, uterus, vascular system and lung. They theorize that a pocket of these uncommitted cells might remain in the spleen though adulthood. In addition to regeneration of islets, these cells might also produce bone cells - suggested by findings from other researchers - or potentially even cells of the nervous system, development of which depends on the correct production of Hox11.

"We know that if you have a major loss of blood, the spleen is turned on to supplement the bone marrow in replenishing your blood supply. We may find that the spleen kicks in to help with many more biological emergencies. What has been considered a practically unnecessary organ may actually provide critical healing cells," says Faustman, an associate professor of Medicine at Harvard Medical School.

She adds, "This data also shows the kind of payback that can come from studies of lower animals like newts and sponges. Combining the knowledge of Hox11's role in those animals with what we'd found about islet cell regeneration in mice helped us find this previously unknown example of normal, controlled Hox11 expression in an adult mammal."

Co-authors of the SAGE KE report are first author Shohta Kodama, MD, PhD, of the MGH Immunobiology Laboratory, and Miriam Davis, PhD, of George Washington University. The group's research is supported by grants from the Iacocca Foundation. Founder Lee Iacocca is also spearheading an effort to raise money for a clinical trial of the islet-regeneration technique in human patients. For more information about this project, go to http://www.joinleenow.org.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Media Contact: Sue McGreevey, MGH Public Affairs

Physician Referral Service: 1-800-388-4644
Information about Clinical Trials

[kevin]

Link: http://www.wired.com...html?tw=rss.TEK

---

Cells That Go Back in Time
By Kristen Philipkoski
02:00 AM Apr. 08, 2005 PT

Lop off a newt's leg or tail, and it will grow a new one. The creature's cells can regenerate thanks to built-in time machines that revert cells to early versions of themselves in a process called dedifferentiation.

Researchers who study this mechanism hope one day to learn how to induce the same "cell time travel" in humans. If the cells go back far enough, they become stem cells, which researchers believe hold promise for treating many diseases. Stem cells, which are often taken from embryos, are unformed and have the ability to become many different types of cells. If researchers succeed in inducing this cell time travel, they will also eliminate the ethical issues surrounding embryonic stem-cell research, because no embryos would be destroyed to obtain the cells.

The research is in its infancy, but a 2001 discovery jump-started the field of study. Mark Keating, Christopher McGann and Shannon Odelberg applied a protein extract derived from newts to mouse muscle cells. To their surprise, the protein extract transformed those muscle cells into stem cells in just 48 hours, which means the mouse cells would have the ability to regenerate.

No one expected the experiment to work. Previously, scientists believed that once mammalian cells became muscle, bone or any other type of cells, that was their fate for life -- and if those cells were injured, they didn't regenerate, but grew scar tissue.

But Keating's experiment introduced the possibility that, under the right circumstances, humans -- who are 99 percent genetically similar to mice -- might one day be able to regenerate their own cells. Those regenerated cells could be used to treat disease.

"For those of us who want to understand what happens in dedifferentiation, our ultimate goal is to be able to form a pool of stem-cell-like cells that would be able to repopulate the organ or tissue you're trying to repair," said Catherine Tsilfidis, a scientist at the Ottawa Health Research Institute who has reproduced Keating's findings, which she describes as "beautiful."

In newts and some other animals with the ability to regenerate, cells at the site of an injury can revert to their embryonic stem-cell stage and can become another type of cell in that creature's body. In other words, a skin cell can dedifferentiate into a stem cell, then regenerate into a muscle cell or another completely different type of cell.

Tsilfidis and her colleagues are now trying to pinpoint which genes are responsible for kick-starting newt dedifferentiation. They published findings in the March 23 issue of Developmental Dynamics identifying 59 DNA fragments that seem to play a role in newt forelimb regeneration, and Tsilfidis believes many of those gene fragments have counterparts in humans.

"Whether (those genes) can actually induce dedifferentiation is yet to be determined," Tsilfidis said. While the genes were active during maximum dedifferentiation activity, she said, so much is going on in cells after a newt's forelimb is cut off that it's difficult to pick out specific dedifferentiation genes.

While some cells are dedifferentiating, others have already begun regenerating and differentiating, or becoming specialized cells. They're performing activities like healing wounds or growing blood vessels, so it's difficult to pin certain genes to specific activities.

Researchers are trying to learn similar lessons from other creatures that have the ability to regenerate, including starfish, zebrafish, earthworms and lobsters.

Adult human bodies do contain some stem cells, but they are rare.

"Maybe only one in a million cells in a particular region might have that regenerative capacity you're interested in," said Robert Naviaux, who studies cancer and stem-cell differentiation, and is co-director of the Mitochondrial and Metabolic Disease Center at the University of California at San Diego. "Stem cells are more concentrated in certain locations like human umbilical cords, blood and bone marrow, and certain areas of the brain around the ventricles."

People who believe it's unethical to destroy any embryos, even those abandoned and destined for destruction at in vitro fertilization clinics, have touted adult stem cells as an ethical choice. The field has seen some success, but many researchers believe adult stem cells have less "plasticity," or ability to become different types of cells.

Others have promoted various schemes for getting around the embryo conundrum, but none has received a unanimous stamp of approval from scientists and religious groups or others who oppose the destruction of embryos.

But at least one religious leader believes the ability to use dedifferentiation to create human stem cells would eliminate the controversy.

"I believe that dedifferentiation -- the direct conversion of a somatic cell into an embryonic stem cell -- is the holy grail for those seeking morally acceptable alternatives to the destructive embryo research now required to obtain (embryonic stem) cells," said Father Nicanor Austriaco, a molecular biologist and Catholic priest in Washington, D.C. "You would also be able to get immunocompatible (embryonic stem) cells from every patient by simply dedifferentiating his or her cells. This would be an amazing discovery."

[kevin]

Link: http://www.eurekaler...h-rft042705.php

---

Researchers feed tiny pills of RNA to planarians to identify genes essential for regeneration
Work at University of Utah also establishes planarian as genetically sound model for human biology

The normal freshwater planarian Schmidtea mediterranea is seen in the foreground gliding over a composite background of some of the 240 phenotypes (defects) generated by the RNA silencing screen.
Credit: Alejandro Sánchez Alvarado

SALT LAKE CITY -- University of Utah researchers-feeding microscopic pills of RNA to quarter-inch long worms called planarians-have identified many genes essential to understanding a biological mystery that has captivated scientists for hundreds of years: regeneration.

In pinpointing the genes, the U School of Medicine researchers have established the planarian as a genetically sound model for human biology, to take its place alongside Drosophila (fruit flies), C.elegans (another worm), zebrafish, and mice.

The study, to be published in the May issue of Developmental Cell, employed the first large-scale use of RNA interference (RNAi) to silence planarian genes to identify their role in the worm's biology, according to Alejandro Sánchez Alvarado, Ph.D., principal investigator and U medical school associate professor of neurobiology and anatomy. The U team's work shows that planarian genes can be selectively manipulated to study some of the most basic and important areas of biological research: stem cells, homeostasis (tissue loss and replacement), regeneration, and disease.

"Planarian biology has much in common to the biology that you and I share," said Sánchez Alvarado, who last month was appointed a Howard Hughes Medical Institute investigator. "This work opens a whole new window to study aspects of human biology that are barely accessible today."

The planarians used in these studies, also called flatworms, live in fresh water and have a singular ability to regenerate. Chop one in half, and two new worms grow. Their ability to regenerate is so prolific that a tissue fragment only 1/279th of the worm's length can grow into a new planarian. Researchers know that planarian stem cells, called neoblasts, play a central role in both regeneration and homeostasis. But how they do that has remained shrouded in mystery.

Sánchez Alvarado and his research associates used bacteria to synthesize double-stranded RNA that silences planarian genes. The bacteria effectively become tiny pills-five to 10 microns across-that now can be mixed into planarian food. When Sánchez Alvarado and his associates fed the worms dinner, the RNA diffused throughout their bodies.

Sánchez Alvarado and Helen Hay Whitney Foundation postdoctoral fellow Peter W. Reddien, Ph.D., silenced and screened 1,065 planarian genes with RNAi. Specific defects were associated with 240 of the genes that were silenced. About 85 percent (204) of the 240 genes are shared by the genomes of other species, including humans, according to Sánchez Alvarado.

The researchers found that 145 of the silenced genes affect both regeneration and tissue loss and replacement. Some of the genes were essential to homeostasis, but not regeneration, and 35 genes were found to be essential to regeneration, but not homeostasis.

"This tells us that separate genetic pathways for regeneration and homeostasis must exist," Sánchez Alvarado said. "It's a huge step forward for us and opens the possibility of systematic molecular studies to find the genetic cause of regenerative processes in animals."

Silencing planarian genes may also help in studying human disease. Thirty-eight of the genes Sánchez Alvarado and his team silenced are related to human genes associated with diseases, such as ataxia (inability to coordinate muscular movements), bradyopsia (slow vision), and cancer. Only eight of those genes have a corresponding knockout gene in mice. This means researchers may be able to use planarians to learn about human diseases that can't be studied in other animal models.

Another 35 of the silenced genes may shed light on the parasitic platyhelminthes, such as Schitosoma mansoni, which cause disease in millions of people. The genes identified by the U researchers may be required for the survival of the parasites.

"Considering such pathogens are estimated to cause disease in nearly 300 million people throughout the world, these genes might make attractive drug targets," Sánchez Alvarado and his fellow researchers wrote in the study.

The planarian makes an ideal biological model for three important reasons, according to Sánchez Alvarado.

It is amenable to genetic manipulation.
It is an extremely simple organism with little redundancy in its genes, meaning it has fewer genes to carry out specific functions. This makes it easier to identify a gene's function by silencing it and will help how researchers target their efforts on equivalent genes in mice or zebrafish, for example.
It is inexpensive to study.
Now that Sánchez Alvarado and his colleagues have opened the door to understanding regeneration by identifying key genes in the process, the U researcher predicts, with aid of the planarian, more discoveries are on the way.

"Our limitations right now are how many experiments we can do in a day," he said. "The mystery of what makes regeneration possible, particularly in these animals, is on its way to finally being resolved."


###
Other authors of the study include Peter W. Reddien, Ph.D, Helen Hay Whitney Foundation postdoctoral fellow, Kenneth J. Murfitt, and Joya R. Jennings, all of the University of Utah Department of Neurobiology and Anatomy in the School of Medicine; and Adam L. Bermange, currently at the London Research Institute.

This news release and a downloadable, high-resolution photograph will be available at this Web site at noon (EST) on Monday, May 2. http://www.utah.edu/...y/planaria.html

For Information Contact:
Alejandro Sánchez Alvarado, Ph.D., (801) 581-3548
Phil Sahm, Public Affairs Office, (801) 581-2517

[kevin]

Link: http://www.betterhum...97/Default.aspx

---

Working Muscle Grown from Scratch
Tissue engineering feat could lead to repair and replacement of damaged muscles

06.20.2005 @10:39 AM
New muscle complete with blood vessels has been grown from scratch in the laboratory and implanted into a living mouse.

The muscle was grown by seeding a sponge-like, three-dimensional plastic scaffold with myoblasts and endothelial cells, precursors to skeletal muscle and blood vessel cells respectively.

Connective tissue cells called fibroblasts provided a crucial third ingredient.

"The idea is that this hopefully will be used to repair or replace damaged muscle tissue when needed," says lead researcher Shulamit Levenberg of the Technion-Israel Institute of Technology.

A muscle biopsy could in the near future provide the seed cells for growing a person's own engineered replacement muscle, says Levenberg.

The key to the technique's success is the growth of tissue with its own blood supply. Engineered tissue has typically been implanted into the body without blood vessels, as the body itself grows and provides them.

"Although this approach has been useful in many tissues, it has not been as successful in thick, highly vascularized tissues such as the muscle," says Levenberg.

By adding blood vessels before implantation, Levenberg and colleagues from Technion and the Massachusetts Institute of Technology showed better success with implantation.

The researchers implanted the engineered muscle in three groups of living mice.

The muscle was placed beneath the skin of the back and within a thigh muscle, as well as to completely replace an abdominal muscle segment.

The transplanted muscle grew and developed in the mice, and the built-in blood supply boosted its chance of survival and of connecting with the mice's own blood vessel networks.

The research is reported in the journal Nature Biotechnology (read abstract).

Copyright © 2005 Betterhumans

[caver]

This is very interesting http://www.coe.berke...005/conboy.html

Edited by Mind, 12 February 2012 - 03:16 PM.

[Karomesis]

the question is not"if" but "when".

We ask ourselves; when the truly incredible becomes the plebian, how much is it to accredit the insane with a sentiment of authenticity?

MY question to bates, prometheus and others in biotech is this.....When we begin to rejuvenate various organs to a biologically healthy age, how many extra years do you think will be added unto us? Aside from the extra "SENS' maladies that will plague our feeble days.

[eternaltraveler]

why can't you regrow CNS neurons...

[John Schloendorn]

how many extra years do you think will be added unto us

There is only one way to find out.

[John Schloendorn]

I'd bet my life on some mix of the following... This is not nice and I hate to be a member of the first prospective guinea pig generation. No cryonics contract will help us if this goes wrong.

- Rejuvenate existing neurons via molecular SENS interventions until we can think of some way to do the replacement properly
- Rejuvenate existing neurons via fusion with young cells
- Forget about keeping the precise connections, hope that a mixture of activity-directed self-organization and doing it very slowly will produce personality changes about as gradual as daily life (though I personally think we can tolerate a considerably faster rate of change)

[John Schloendorn]

Anyway, I'd like to comment on the original topic of this thread, that I think the scaffold strategy is quite remarkable, if one pins down the right mix of growth factors to stick to it for each target organ. For muscle it should already be a great thing to play with given the previous stanford work on delta/notch.

[Karomesis]

Prometheus, any recomendations for a research study on CNS nuerons? If you had access to a lab perhaps, Maybe an educated guess or two about possible solutions to this dillema? [glasses]

I am not a biotech know it all, but I think the more we discuss matters like this the sooner someone will hit the nail on the head and come up with a creative breakthrough.

Prometheus, what is it you are currently involved in? if you don't mind me asking.

[caver]

Here's more info on ES research addressing CNS cells. http://www.jneurosci...full/24/22/5258

CNS neurons in aged mammals have more extended derdri, this works to counter neuronal death. Perhaps introduced ES can be genetically or hormonally cajoled to excellerate this growth. New CNS neurons could then become incorporated more rapidly into many of the same matricies as the aging cells.

[Lazarus Long]

Here is another finding. It might be nice to get our hands on the source article. This discovery implies another unforeseen role for cell apoptosis.

Scientists find early key to regeneration
Dec 13, 2006, 20:45 GMT

BOSTON, MA, United States (UPI) -- U.S. researchers have determined some cells must die for regeneration to occur, moving science closer to understanding how a limb or organ can be grown.

The Forsyth Institute researchers say their findings might provide insight into mechanisms necessary for therapeutic regeneration in humans, potentially addressing tissues that are lost, damaged or non-functional as a result of genetic syndromes, diseases, accidents, and aging.

Using Xenopus tadpoles for their study, the Forsyth team examined the cellular underpinnings of regeneration.

The research, led by Michael Levin, director of the Forsyth Center for Regenerative and Developmental Biology, found apoptosis has a novel role in development and a critical role in regeneration.

'We were surprised to see that some cells need to be removed for regeneration to proceed,' said Ai-Sun Tseng, the study`s first author. 'It is exciting to think that someday this process could be managed to allow medically therapeutic regeneration.'

The findings are to be published in the Jan. 1 issue of the journal Developmental Biology.

Copyright 2006 by United Press International

[xanadu]

I believe the way we will do it in the future is by replacing all organs or all cells or by replacing and or renewing our DNA. These are all totally related techniques and vary only in sophistication. The basic idea is that we will take the old falling apart dna we have and restore it to the state it was at age 18 or perhaps at birth.

Computers will do this job. They will look at our dna and make on a disc a copy of how it should be. Any flaws in your original dna will be corrected unless you don't want that. This corrected dna will then be put into a factory nanobot which will produce messenger rna or dna which will do the actual work.

Whole new organs can be produced in the lab and used to replace your failing ones. Or, better yet, injected and used to replace the organ from the inside. This will be done by a similar process the way cancer invades and takes over organs and tissues. Instead of replacing the old organ with an undifferentiated mass, it will be the new organ. At a higher level of sophistication will be overhauling the cells themselves. This will be done by an injection of specially manufactured messenger rna which will replace or repair your present dna.

I'm not saying any of this is brand new, but this is how it will be done. Aging will be a thing of the past. Now if we can just figure out how to feed, house, clothe and so on our present population and control growth, then this can be allowed to be put into place. Until then, I say it should be available to those who can pay for it.

[olaf.larsson]

How are the stem cell going to be placed in the right places?

[xanadu]

" How are the stem cell going to be placed in the right places?"

olarrson, that remains to be worked out. It is done in the embryo and we are working on deciphering the system. That is simply one possible technique. I like the cell rejuvenation idea myself. Produce legions of factory made repair rna cells programmed with the correct dna code. They will go over all the dna in the cell and and by repairing it, will upgrade it to the new or original version of your dna. At some point in time the factory itself will be implanted in your body and will be so tiny as not to be an issue. It will also contain a virtually inexhaustible power supply. The old idea of replacing a whole organ with another either a transplant or lab grown, is yesterday's technology. We won't be using that much longer.