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Organ & Tissue Replacement and Regeneration

regenerative medicine mmp14 aging body-replacements

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#61 John_Ventureville

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Posted 29 April 2007 - 08:44 AM

The man behind the curtain will give everyone a new one.

John : )

#62 xanadu

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Posted 29 April 2007 - 06:54 PM

Actually, I should have titled it "rejuvenation" of cells rather than replacement of cells. Replacement is the old tec which will be pushed out into the street by rejuvenation of the cell's DNA. We already know that there are units inside the cells that go over our DNA correcting and repairing any mistakes that get made during replication or at other times. I don't recall offhand what they are called but they have a name. I believe they are specially programmed bits of RNA made into a sort of robot. What we need to do is learn how to produce these units and improve their function. Right now all they seem able to do is correct small and obvious flaws in the code. Why is it our DNA deteriorates over time and these mistakes are not corrected?

wbreeze, the brain and heart are the most important organs, the brain certainly is. They will be rejuvenated the same way as the rest of our tissues. As the DNA is brought back to the condition it was in at our peak, the cells will function as they did back then and the tissues and organs will once again be young.

Growing new organs in the lab to transplant is a dead end tec. It will be used in the future only for extreme cases such as when the organ was subjected to trauma such as violence, poisoning or other acute events.

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#63 John Schloendorn

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Posted 29 April 2007 - 07:41 PM

Why is it our DNA deteriorates over time and these mistakes are not corrected?

Our native repair machinery can only correct transient mistakes, in the form of pieces on our chromosomes which are not DNA (e.g. because a free radical bumped into them and changed it into a different chemical). If DNA is replicated while damaged, the result may be a mutation, i.e. something that is DNA but has a wrong sequence. Once established, mutations cannot be recognized directly or corrected. It would take a fundamentally new sort of technology to compare DNA sequences against a blueprint and correct the mutations.

Do you think doing this would do anything about "junk" diseases, such as beta-amyloid that has been accumulating?

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#64 xanadu

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Posted 29 April 2007 - 09:06 PM

John, I think doing this would take care of alzhiemers as well as everything else. Unless you had it programmed into your genetic code. Many people are pre-programmed for disease. Mutated cells are usually killed by white cells, often mediated by antibodies or other mechanisms. Cancer cells, for instance, are produced on a regular basis but are destroyed regularly. As this mechanism breaks down, we age and die.

It all goes back to what I was saying about finding your original DNA code, correcting it for any congenital errors and using that as a template to rejuvenate the whole entire body and all it's processes. This is the only approach that will work in the long run. Giving someone a new heart or kidney may give them additional years but every tissue and cell has to be fixed if we are to cure aging. Replacement by other tissues and organs is a losing battle. Besides histocompatibility, there are other issues such as physically connecting the tissues to support systems. How would you replace the brain? Only rejuvenation from within can possible fix that. Then there are nerves, connective tissue, etc etc.

The hard part is going to be in manufacturing the units that will fix up our DNA. This is done now but on a low level. When a cell divides if the new DNA is not correct, sometimes it can be repaired if it's just a few pairs of the building blocks that are wrong. Sometimes the whole cell is tagged for removal. We are struggling along with a primitive cell repair mechanism and that is what ultimately must be fixed.

Going back a few million years in evolution you did not have any great need for organisms to survive a long time. There was never a great incentive for nature to develop this. Once an animal was past it's prime, it's chances of reproducing were greatly reduced. If an animal had a lucky mutation that allowed it to live several times longer than it's relatives, how would this be selected for and preserved? Old feeble animals are a drag on the community to support. They do not gather as much food or do anything else as well. We need to develop this in the lab because nature left to it's own devices will not likely ever come up with it.

#65 maestro949

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Posted 11 September 2007 - 07:17 AM

This would be a great Plan B for rejuvenating organs in the case that stem cells don't live up to their promise over the next few decades. If we can't rejuvenate them, replace them with versions grown in human-pig Chimeras.

The research, presented at the British Association's Festival of Science in York, centres around tricking the body's immune system to believe that pig organs are human.

This is done by creating pigs carrying genes which alter key molecules on the surface of organs, hiding their origin from the human immune system.

It is hoped the humanising of the organs will allow transplants to succeed.

Hearts, lungs, kidneys and other organs could also be used to test new medicines, cutting the risk of dangerous reactions when they are given to humans.


Link: http://www.dailymail.co.uk

Edit: fixed title which indicated that the organs were human organs.

Edited by maestro949, 11 September 2007 - 05:51 PM.


#66 Luna

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Posted 11 September 2007 - 09:23 AM

Wait, is it pigs with human organs or pigs with organs which will not be rejected by humans?..

"centres around tricking the body's immune system to believe that pig organs are human."

Sounds more like pig organs for humans.. *oink* *oink*

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#67 bob_d

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Posted 11 September 2007 - 09:38 AM

Sounds more like pig organs for humans.. *oink* *oink*

yes. they on lychange the immune markers of the organs but not their structure. I wonder why the journalist guy didn't take a stance against the eu laws which delay the marketing of this technology, that could easil save thousands of lives a year by ending organ shortage and abolishing the waiting list for transplantion.

But EU regulations mean that the researchers have so far been refused permission to breed from the pigs.

This, combined with a 13-month delay for Home Office approval to inject the gene into the pigs, means further research may be carried out in the U.S.



#68 Live Forever

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Posted 11 September 2007 - 05:10 PM

That is pretty sweet. Whenever one of your organs wears out, just grow another one in a pig. I wonder how much a system like this would cost? Probably not very much. (and would cut the wait times for organ donation down significantly)

#69 maestro949

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Posted 11 September 2007 - 05:57 PM

Wait, is it pigs with human organs or pigs with organs which will not be rejected by humans?..


Good catch. I fixed the title.

That is pretty sweet. Whenever one of your organs wears out, just grow another one in a pig. I wonder how much a system like this would cost? Probably not very much. (and would cut the wait times for organ donation down significantly)


Sweet indeed. You could keep a barn full of them. When it's time for a replacement organ you get compliments of a hickory-smoked prosciutto dinner too.

#70 Live Forever

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Posted 11 September 2007 - 09:45 PM

That is pretty sweet. Whenever one of your organs wears out, just grow another one in a pig. I wonder how much a system like this would cost? Probably not very much. (and would cut the wait times for organ donation down significantly)


Sweet indeed. You could keep a barn full of them. When it's time for a replacement organ you get compliments of a hickory-smoked prosciutto dinner too.


..or pay someone else to keep a barn full of them. Actually, all you would probably need was a few of them (4 or 5?) at different ages. Like every 6 months or something they could give birth to another one with your organs, and you could pay someone to keep it for you until you needed one. You could probably pay a monthly fee of 50 bucks or whatever to keep them all cared for. (and if they get too old, they could sell them for pork like they usually do, to recoup some of the cost)

#71 JonesGuy

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Posted 12 September 2007 - 01:16 AM

What about the pig retrovirus (there was concern of transferring to people)? Have they excised those genes, or something?

Edit: I think the last time I saw someone mention this, it was Carbon X

#72 Karomesis

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Posted 12 September 2007 - 01:25 AM

impressive posting Maestro [thumb] keep up the good work my friend. :p


I am firmly convinced that society will take the path of least resistance when it comes to these therapies, and how they pertain to life extension. They're unconciously progressing life extension therapies, the more hype/market madness there is, the faster these cutting edge therapies will be available to the average joe.

#73 lauritta

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Posted 12 September 2007 - 10:59 PM

People, this is old news!
In my lab, one of my classmates was working with this kind of research:

Xenotransplantation. 2006 Jan;13(1):75-9. Links

Expression of human soluble complement receptor 1 by a pig endothelial cell line inhibits lysis by human serum.
Manzi L, Montaño R, Abad MJ, Arsenak M, Romano E, Taylor P.
Laboratory of Cellular and Molecular Pathology, Centre for Experimental Medicine, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela.

The importance of complement activation and naturally occurring anti-pig antibodies in the hyperacute rejection (HAR) observed in models of pig-to-human xenotransplantation is well established. To overcome this, much effort has been dedicated to preparing transgenic pigs by knocking out Galalpha(1-3)Gal expression in these animals, or knocking in the expression of human complement regulatory proteins (CRPs), such as CD59 or decay accelerating factor. A soluble form of another membrane CRP, complement receptor type 1 (CR1), has also been shown to inhibit complement activation. Here, we show that transfection of a pig endothelial cell line with a truncated form of human soluble complement receptor 1 (sCR1) almost completely protected these cells from complement-mediated lysis by human AB serum. Pigs genetically manipulated to express human sCR1 may represent an additional strategy to inhibit HAR of pig-to-human transplanted organs.

PMID: 16497215 [PubMed - indexed for MEDLINE]

#74 dannov

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Posted 14 September 2007 - 02:58 PM

Geez, you're cute laur! *grin*

Anywho, it's new news to me. I've heard for years that they have been trying to find ways to trick the human body into accept pig organ donations, but I had no idea until now just how close they were. To me, it just doesn't seem right--raising extremely intelligent animals (pigs are actually cognitively more capable of learning than dogs) just to be used for their organs. People *could* just take care of themselves and the organs that they have--always a novel idea. :)

#75 eternaltraveler

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Posted 14 September 2007 - 03:49 PM

lets try to keep the flirting to a minimum in the bioscience forum :))

I think what's new Lauritta is they think they are ready to start clinical trials again.

1: Rev Med Suisse. 2007 Jun 27;3(117):1632-6.

[Xenotransplantation, soon a clinical reality?]
[Article in French]

Sgroi A, Baertschiger RM, Morel P, Buhler LH.

Unité d'investigations chirurgicales, HUG, 1211 Geneve 14.

Organ transplantation has encountered great development during the 80's. However, the number of organ donations and transplantations performed stabilized during the 90ies, with a concomitant increase of patients on the waiting list. Xenotransplantation, i.e. the use of animal organs for transplantation to humans, is one among various alternatives to human organ donation. Xenotransplantation offers several advantages, e.g. it would be possible to transplant all patients at an early stage of their disease. The main barriers to xenotransplantation are the strong immunological responses that human develop against animal antigens and zoonoses. To overcome these hurdles, genetically modified pigs have been engineered by cloning and could allow the initiation of new clinical trials in a near future.

PMID: 17708231 [PubMed - in process]

#76 eternaltraveler

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Posted 14 September 2007 - 03:50 PM

of course what's new to the mainstream media may be 20 years old.

#77 maestro949

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Posted 14 September 2007 - 04:12 PM

To me, it just doesn't seem right--raising extremely intelligent animals (pigs are actually cognitively more capable of learning than dogs) just to be used for their organs.


Maybe you're right, perhaps we just stick with the more humane butchering and eating of them. Though if we're already doing that, are they really going to miss an organ or two?

#78 Luna

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Posted 14 September 2007 - 04:37 PM

I think what's new Lauritta is they think they are ready to start clinical trials again.


[wis] [glasses] [tung]

#79 dannov

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Posted 14 September 2007 - 05:35 PM

To me, it just doesn't seem right--raising extremely intelligent animals (pigs are actually cognitively more capable of learning than dogs) just to be used for their organs.


Maybe you're right, perhaps we just stick with the more humane butchering and eating of them. Though if we're already doing that, are they really going to miss an organ or two?


I don't eat pig, and no, I'm not Jewish/Moslem nor a vegan/vegetarian.

And ya Elrond, I was merely making a scientific observation, you know how it is! :D

#80 kevin

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Posted 24 September 2007 - 11:19 PM

It's been a while since anyone posted in this thread.. enjoy this article.. I did.

http://www.tjols.com/article-261.html

From Rehab to Regeneration
Military-supported researchers take on the challenge of growing new limbs and other body parts.

By Ann Parson

“War is cruelty,” said General William Sherman, and one measure of the cruelty suffered by today’s soldiers in Iraq is the number of amputated limbs. Radical improvements in emergency triage, medical evacuation and body armor mean more soldiers are surviving battlefield trauma than ever before. The unfortunate corollary is that more survivors are living with harsh injuries.

In World Wars I and II and the Korean War, fewer than 2 percent of total casualties were amputations. The wars in Afghanistan and Iraq, however, have produced amputations at more than twice this rate. As of June 1, according to the U.S. Army Medical Command, 607 American veterans of Afghanistan and Iraq were without one or more limbs. But two new military-sponsored research projects in regeneration could revolutionize an amputee’s prospects.

Here’s the futuristic vision: Were a soldier’s eye tissue to be scorched by chlorine gas, his intestine ruptured by small arms fire, or her arm blown off by a roadside bomb, such a soldier might be transported to a regenerative medicine complex where, ideally, his or her own cells would be put to work to create new ocular tissue, new intestinal tissue or a new arm. This vision applies easily to non-military needs as well—the diabetic whose limb is amputated, the machinist who accidentally loses a finger, the infant born without arms, the elderly person with macular degeneration.

A project funded by the U.S. Department of Defense seeks to heal a wound’s damaged tissue by regenerating the tissue as opposed to the body’s routine healing method of creating scar tissue. The project is run by the Department’s chief research and development agency, the Defense Advanced Research Projects Agency, or DARPA, which has a record of pursuing high-risk, high-payoff science. Last year, it launched Phase 1 of the Restorative Injury Repair Program, or RIR, which has received $14.4 million in funding so far, according to spokeswoman Jan Walker. Injuries that might be healed regeneratively range from penetrating wounds to “chemical and thermal burns, musculoskeletal injuries, blast overpressure, etc.,” according to DARPA.

A smaller but equally innovative initiative called the Soldier Treatment and Regeneration Consortium, or STRaC, is already heading toward preclinical and clinical studies. STRaC’s partnership of military, academic and industry researchers, which include the U.S. Army Institute of Surgical Research, the U.S. Army Medical Research and Materiel Command, the Walter Reed Army Medical Center, the Wake Forest Institute for Regenerative Medicine, the Trauma Institute of San Antonio and Honolulu-based company Tissue Genesis, have been given the task of growing a fully functioning finger by the year 2011.

For the RIR program, the first benchmark is even more immediate—and more daunting. By the end of Phase 1—or May 2008—researchers must get a blastema to form in a non-regenerating wound site in a mammal, or risk losing their funding. A blastema is a smallish mound of cells that appears at the margin of, for instance, a lobster’s lost claw, from which sprouts a new claw. When a lobster drops its claw, the wound sends out molecular signals which inform nearby cells to dedifferentiate; that is, they become less specialized and revert back to a stem-cell-like state. These cells, which form the blastema, in turn yield the wide range of specialized cells that are needed to remake the limb and all of its various tissues.

Wounded animals that create blastemas generate new tissue rather than scar tissue. Therefore, the blastema represents a pivotal biological entity—a boundary, as it were, between scarring and regeneration that scientists hope to better understand. The immediate hitch is that mammals don’t normally produce a blastema, at least not the kind that results in the recreation of a full-fledged appendage.

“DARPA doesn’t go for baby steps,” says Susan Braunhut, a professor of biological sciences at the University of Massachusetts at Lowell and an RIR participant. “They have asked us to do what has never been done before. This is not incremental science. They believe, and I believe along with them, that we are at a point in science where this has been made possible.”

With no laboratories of its own, DARPA has assigned the project to two research teams that together represent an interdisciplinary mix of scientists from nine academic research labs and one biotech company. One team is coordinated by Stephen Badylak, the director of the Center for Pre-clinical Tissue Engineering at the University of Pittsburgh’s McGowan Institute for Regenerative Medicine. Ken Muneoka, a Tulane University molecular biologist who specializes in vertebrate limb formation, heads the other group. The program is slated for two phases, each of which will last two years.

The RIR program and its strikingly difficult assignment might not have made it onto DARPA’s agenda were it not for several recent developments. First, it was only in the mid- to late-1990s that researchers on several continents arrived at a basic understanding of what happens in the blastema at the cellular and molecular levels that enables an animal to grow back a missing appendage, be it a lobster’s claw, a newt’s leg, or a snail’s mantle. While the process of cells dedifferentiating back into a stem-cell-like state so that prodigy cells can then re-specialize to form tissues anew is a vital part of producing a new limb, it’s not the whole story, says Jeremy Brockes, a biochemist at University College London. Brockes, who has been at the forefront of this research for many years, notes that cells from surrounding tissues, like the dermis of the skin, influence the creation of the new limb but don’t necessarily dedifferentiate to do so.

A second area where scientists are making progress is the study of gene expression and the ability to identify genes that either promote regeneration or block it. A third advance has to do with signaling molecules, about which, the McGowan Institute’s Badylak says, “we know one hundred times more today than we did five years ago.” The extracellular matrix that exists between cells is chockfull of proteins and smaller signaling molecules that play an integral role in regulating regeneration. Since some of these signalers encourage tissue to regenerate, rather than to scar, identifying such factors is a priority for RIR scientists.

“The idea here,” says David Gardiner, a developmental biologist at the University of California, Irvine, who is also participating in RIR, “is that regeneration is a basic biological property and widespread in animals.”

Indeed, the so-called diva of regeneration, the salamander, can regenerate its fore- and hind limbs, tail, spinal cord, optic nerve, retina and lens, a section of the heart’s ventricle, and its upper and lower jaw, while a mammal can do none of these things. Still, a mammal is far from a regenerative laggard.

Take a human fetus, whose appendages retain a high degree of regenerative ability up through the 16th week of gestation. And a healthy human adult, who loses an estimated 10 billion cells each day—from intestine, skin, hair, blood, bone, muscle and elsewhere—renews them in good time. Our livers can grow back after as much as one-half is removed. Fingertips in both children and adults can also regenerate. “Sure,” the DARPA quest is incredibly difficult, allows Jon Mogford, RIR program manager, “but we aren’t asking the human body or a mammal to do something it’s not capable of doing.”

Although “the seedling” for the RIR program was planted a year or two before 9/11, when the Iraq war came along, there was a shift in the federal allocation of research funds, says David Vorp, associate professor of surgery and bioengineering at the University of Pittsburgh. “Research dollars earmarked for biomedical and clinical applications decreased, and funds increased for defense research having to do with soldier fixing and healing” he notes. “The funding trend is away from more traditional applications to beginning to think outside the box.”

But questions remain: Is DARPA’s goal of replacing scar tissue with regenerated tissue too ambitious? Will it be possible to talk the adult body out of its normal response to a wound—healing through scarring—and talk it into developing new tissue the way it did as a fetus? Once an injury occurs, scarring immediately commences—can it be immediately halted?

Brockes, who is not participating in RIR, agrees with the project’s objective of attempting to derive a mammalian equivalent of a blastema. “If I were going to work on trying to get human limbs to regenerate, I would choose that goal as well,” says Brockes, who discussed this very possibility—engineering a blastema—and the prospects for limb regeneration in adult vertebrates in a 2005 Science article. What makes this a particularly reasonable approach, he adds, is that the blastema is an autonomous structure.

Experiments from the 1970s demonstrated that when a salamander blastema’s mound of cells is transplanted from the margin of a limb stump to, say, the fin or even the chamber of the eye, “it will go ahead and give you a leg,” Brockes says. This is due to blastemal cells having what is called positional memory. In a salamander, cells at the margin of the loss know unequivocally that they are going to create a leg, and nothing can change their mind. The instructions for “leg” are encoded in their DNA.

Many tissue engineers might think that a better approach to replacing a leg than prompting a blastema to form would be, in the tradition of tissue engineering, to seed a three-dimensional scaffold made of dissolvable plastic with cells, extend the scaffold out from the limb stump and wait for the scaffold’s cells to mature into the desired tissue and structure. “But the fact is, nature doesn’t do this,” Brockes says. “Nature recreates at whatever level you amputate the limb.” Tissue engineering a new limb, Brockes believes, would be tremendously difficult, for it would hinge on figuring out complex interactions between molecules and different cell types so that the leg’s necessary tissues—bone, muscle, blood and skin—would align properly. It appears more promising to get cells in the blastema to do the work for you.

Brockes, who, on the whole, believes that humans might someday regenerate their appendages, cites another reason for optimism. In nature, he notes, even closely related species vary in their regenerative prowess. The only salamander species that can regenerate the lens of its eye, for instance, is the aquatic newt, whereas an axolotl, although a fabulous regenerator of other structures, lacks the ability to regrow its lens. Such examples add weight to the idea that the potential for regeneration dwells in all species, that those species that can’t regenerate an entire structure have lost some biological component that would allow them to do so, and that therefore, with some prodding, even humans might recover the capacity.

Muneoka, the Tulane molecular biologist, who has been studying how limbs regenerate for 28 years, has two additional reasons for believing that humans might be cajoled into re-growing complex parts. Years ago, he recalls, when he began studying salamander regeneration, “I asked myself, how different is limb formation during [in utero] development from the same process in regeneration” in an adult animal. “The answer is, they are very similar. I realized that if that’s the case, and humans grow limbs during development, why shouldn’t they be able to regenerate a limb?”

His second reason is based on what he knows about fibroblasts, the cells that in humans produce the collagen fibers in scar tissue. It turns out that in salamanders, fibroblasts, instead of leading to scarring, trigger the regeneration response. “Fibroblasts in both humans and salamanders carry spatial information critical for identifying what parts of the body are missing,” Muneoka notes.

Researchers have found that if an animal scars, it doesn’t regenerate; and if it regenerates, it doesn’t scar. The implication of this antithetical relationship is that if you could close the door on scarring in humans, you might open it to regeneration. “That’s certainly one step, but it probably wouldn’t be enough,” says Muneoka. He and his RIR teammates, therefore, while training their sights on fibroblasts, are also investigating other early events that occur after an injury—the inflammatory response, for instance—to gain new insights into how the scarring process might be redirected.

Badylak’s team, meanwhile, is studying the extracellular matrix. “We’re asking the question, ‘How can we harness some of the biological signals in the extracellular matrix to change the way an adult mammal heals?’” he says.

Badylak, who is an unusual combination of M.D., Ph.D., and veterinarian, stumbled across the extracellular matrix’s extraordinary capacity for regeneration more than 20 years ago. He happened to extract a layer of intestinal tissue in a dog that, when transplanted, yielded functioning tissue for the dog’s aorta.

What he has discovered since is that matrix harvested from the right place, when applied to a wound, invites regeneration and discourages scarring. The procedure can be used for reconstructing the urinary bladder, treating a torn rotator cuff or diabetic foot ulcer, replacing the lining of the brain (dura mater), and repairing a large or small finger cut. A powder version of matrix harvested from pig intestine reportedly was responsible for growing back three-eighths of the outer digit of a man’s middle finger—bone, nail and all.

As for smaller cuts and burns, “people in the lab swear by it,” says Scott Johnson, a staff scientist in Badylak’s lab. The reason the matrix does not elicit an immune-system response, according to Badylak, is because it consists mostly of proteins and other highly conserved molecules, and contains no cells. Findings connected to extracellular matrix have spawned some 40 patents and have also resulted in clinical treatments from a unit of Johnson & Johnson and the biotech enterprise Cook Group of Bloomington, Indiana.

Badylak’s RIR team includes a tissue engineer, two cell biologists, an immunologist, a pharmacologist, and a specialist in amphibians, each of whom is coming at the single objective of minimizing scarring and maximizing regeneration from a different angle:

• Badylak’s McGowan lab is studying biological signals within the extracellular matrix;

• Braunhut of the University of Massachusetts is running experiments to see whether injected matrix can prompt growth in the toes of mice;

• Shannon Odelberg at the University of Utah is working to identify genes that make the extracellular environment appropriate for regeneration and, therefore, for the blastema’s formation;

• Ellen Heber-Katz at The Wistar Institute is looking at the role of immune cells and the inflammatory response;

• Lorraine Gudas at Cornell University is studying cell differentiation;

• Hans-Georg at Northwestern University is testing the ability of regulatory genes to control the generation of stem-like blastema progenitor cells from muscle.

These teammates are happy to be working with people outside their disciplinary silos. “Here I was in wound healing, and I’ve never talked to a salamander regeneration person,” says Braunhut. “Why wasn’t I talking to them?”

Meanwhile, the matrix powder, which Badylak sees as strong evidence that mammals can be directed to regenerate without scarring, is the centerpiece of a clinical trial connected to the Defense Department’s STRaC initiative. Researchers at the U.S. Army Institute of Surgical Research in Fort Sam Houston, Texas, are testing the effectiveness of extracellular matrix by applying it to the finger stumps of five soldiers who have recently lost all or part of their fingers. The powder is to be administered for two weeks, and then the fingers’ length, function and sensitivity will be measured for several months.

“The idea here was to take some of Steve’s technology straight to soldiers,” says Alan Russell, director of the McGowan Institute. “No one thinks we’ll go past a joint. But even if you could grow back half a centimeter, you would still give a person a better quality of life.”

Investigators are both guarded about their experimental mission—they admit that getting a blastema to form in a mammal by next May is a mighty tall order—and determinedly positive. “All you have to do is look at history, and you know these things can happen,” Badylak says. “Can you imagine if you said, in the year 1900, that we would be able to transplant hearts? You would have been laughed out of town. And now look. Here at the University of Pittsburgh, we transplant an organ every 18 hours.”



Ann Parson is the author of The Proteus Effect; Stem Cells and Their Promise for Medicine, which was chosen by Library Journal for its yearly list of best science books for general readers.

#81 Lazarus Long

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Posted 14 January 2008 - 01:04 AM

In what can almost be seen as a mixed methodology of stem cells and bio-nanotech a living heart has been grown from basic cells and offers a potentially powerful technology for replacement hearts in the now not so distant future. This technology builds off the basic tissues and uses embryonic cells to rebuild replacement cells. I would very much like to see this research after it is fully published.

Scientists create beating hearts in lab

By Julie Steenhuysen 33 minutes ago

CHICAGO (Reuters) - U.S. researchers say they have coaxed hearts from dead rats to beat again in the laboratory and said the discovery may one day lead to customized organ transplants for people.

"The hope would be we could generate an organ that matched your body," said Doris Taylor of the University of Minnesota Center for Cardiovascular Repair. Her study, which appeared on Sunday in the journal Nature Medicine, offers a way to fulfill the promise of using stem cells -- the body's master cells -- to grow tailor-made organs for transplant.

Taylor and colleagues used a process called decellularization to wash away existing cells from the hearts of dead rats while leaving the basic collagen structure intact. They injected this gelatin-like scaffold with heart cells from newborn rats, fed them a nutrient-rich solution and left them in the lab to grow.

Four days later, the hearts started to contract.

The researchers used a pacemaker to coordinate the contractions. They hooked up the hearts to a pump so they were being filled with fluids and added a bit of pressure to simulate blood pressure. Eight days later, the hearts started to pump.

"I have got to tell you, that was the home run," Taylor said in a telephone interview.


HEALING HEARTS

Like many researchers, Taylor and colleagues had been working on a stem cell therapy to try to heal hearts damaged by heart attacks.

A British team last month said they generated mature, beating heart cells from embryonic stem cells that could be used to make a heart patch.

Others have tried injecting heart stem cells directly into the scarred heart in the hopes of regenerating damaged tissue.

The Minnesota team took another approach.

"We recognized that nature has created the perfect scaffold and wondered whether there is a way in the lab to give nature the tools and get out of the way," Taylor said.

She and colleague Dr. Harold Ott, who is now at Massachusetts General Hospital, knew that decellularization already had been used in making tissue heart valves and blood vessels and decided to try it on whole organs. They did the process with rat and pig hearts. But they only reported on the regeneration of the rat hearts.

"We hung these organs in the lab and we washed out all the cells. When you are done, you have this thing that looks like a ghost tissue," Taylor said.

The scaffold is made up of collagen, fibronectin and laminin.


The researchers chose immature heart cells because they thought these were most likely to work. "The hope ultimately -- although we've got a ways to go -- is that we could take a scaffold from a pig or a cadaver and then take stem or progenitor cells from your body and actually grow a self-derived organ," she said.

Taylor said the process could be used on other organs, offering a potential new source of donor organs. It also could lead to organs that, in theory, would be less likely to be rejected by the body. Nearly 50,000 people in the United States die each year waiting for a donor heart.

"This is an ingenious step towards solving a massive problem," Dr. Tim Chico of Britain's University of Sheffield said in a statement. "This study is very preliminary, but it does show that stem cells can regrow in the 'skeleton' of a donor heart."


It really is an exciting time to be alive!

#82 mike250

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Posted 14 January 2008 - 03:00 AM

very fascinating indeed. its not too long before we have the same thing done with other body-parts.

#83 niner

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Posted 14 January 2008 - 03:31 AM

Freakin awesome. One thing that's cool is that if you transform stem cells into heart cells and grow them in a Petri dish, at some point they start to spontaneously beat. There might not be much reason why we couldn't create custom scaffolds using 3D inkjet methodology, then seed them with stem cells. Maybe we could make immunocompatible organs that were better than the original.

#84 Lazarus Long

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Posted 14 January 2008 - 04:02 PM

Here is a more in depth article on the same subject.

Team Creates Rat Heart Using Cells of Baby Rats

#85 caston

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Posted 14 January 2008 - 05:18 PM

Could you do this with a brain?

#86 Lazarus Long

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Posted 15 January 2008 - 02:12 AM

Gsnake opened another thread with excellent photos of the subject here

Also Caston I think we are a long way from doing this with a brain as that is a vastly more complex organ but it is a very good question to ask. However even if we could build a brain there are two more critical questions, how do we transfer consciousness (regardless of how we define it for the moment) and how do we effectively re-implant the brain in a subject.

In many respects I think either of these two obstacles can have monumental importance but I suspect that if we can transfer consciousness that the second problem of organ implantation becomes somewhat moot.

Suppose instead of trying to transplant a brain we simply use the methodology to build an entire body with a self supporting brain?

I wonder how much of natal development can be leap frogged with this method?

The researchers here were not trying to do so but the approach begs the question, could an adult heart be built in this manner?

If an adult organ can be built then perhaps an entire adult body.

#87 caston

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Posted 15 January 2008 - 01:53 PM

Laz:

Even just to rebuild parts of the brain would help a lot of people.

Also in terms of doing this with an entire body it might one day be conceivable that a mother of a still born child may be offered this sort of technology
so that she can have her child.

#88 Lazarus Long

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Posted 15 January 2008 - 02:05 PM

Even just to rebuild parts of the brain would help a lot of people.


I agree that will be happening. Rebuilding neural components and even being able to insert them functionally into the brain is feasible in a reasonably short term.

I just want to carefully distinguish replacement repair of Alzheimer's for example with the dilemma of uploading to a transplanted brain. These are two profoundly different applications and set of problems.

Rebuilding a still born child is a tricky issue and no rebuilding should occur if it simply repeats the biology that inflicted the initial problem. Also once we are growing humans in tanks instead of birthing them through sexual based evolution we have crossed a line that many may want to think very carefully about first.

Even motives are of the noblest character may not prevent some terribly damaging results for the application of these technologies. Yes we must embrace this "Brave New world" but we should not do so blindly or blithely. We should never deny the risks or ignore the consequences of our choices.

#89 caston

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Posted 17 January 2008 - 03:21 PM

Well it would be simply fantastic to get a new vascular and respiratory system system every 20 years or so. We just need to look after ourselves so
that we are still here when the option becomes available. I think we should bet that the brain is going to still be difficult to work with and thus err on the side of caution and look after our brains as much as possible.

One idea I had today is do you think it could be possible to use this technology in agriculture?

For instance you could have an ECM for a blueberry or apple. At which point we can start to experiment with building entirely new ECM's from stratch making blueberries the size of apples and apples the size of blue berries perhaps even entirely new fruit never even imagined before. Then we could control the nutrional content of the food.

ECM CAD's could be an important part of synthetic biology.

Edited by caston, 17 January 2008 - 03:24 PM.


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#90 Hedgehog

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Posted 09 February 2008 - 12:16 AM

Hedgehog family member is expressed throughout regenerating and developing limbs.

This same pathway also deals with the regeneration of the zebrafish fins. http://www.eurekah.com/chapter/2542


The problem is that when you regrow something you often need to turn on potentially cancer acting pathways. Which makes it hard for companies to get past the FDA







Also tagged with one or more of these keywords: regenerative medicine mmp14, aging, body-replacements

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