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Brain knitting

April 13, 2006 - Nature - Materials Update - Healing brain and spinal-cord injuries is one of the most desirable, but challenging, goals of regenerative medicine. Molecules that self-assemble into nanoscale filaments may show the way.

A scaffold of nanoscale fibres that self-assembles from small, synthetic protein-like components provides a framework for the regrowth of damaged brain tissue, allowing vision to be restored in hamsters with brain lesions, a team in the USA and China reports.

Rutledge Ellis-Behnke of the Massachusetts Institute of Technology and his co-workers have developed a nano-scaffold, being made of short peptides, it is biodegradable and non-toxic, causes no immune response, is injectable — it self-assembles when the molecules come together in a salty solution — and, because it is composed of nanofibres, allows an intimate interaction between the peptide matrix and the surrounding tissue. The researchers say that it provides a 'permissive environment' that helps cells, such as neurons, regrow and knit together damaged tissue.

The scaffold is formed from peptides containing ionic amino-acids groups, designed so that they will come together spontaneously in beta-sheet structures like those found in proteins. Ellis-Behnke's colleague Shuguang Zhang of MIT has been designing such peptides for several years, tuning the peptide structures to make fibrous aggregates just a few nanometres thick that link up into three-dimensional networks with possible uses in tissue engineering. Several years ago he and his co-workers reported that these scaffolds could support the growth of neuronal cells and the outgrowth of neurites (neuron filaments) in cell cultures.

These promising results were echoed by those obtained by Samuel Stupp's group at Northwestern University in Illinois, who have found that a nanofibre network made from a different kind of self-assembling peptide, with an amphiphilic structure, can form around neuron progenitor cells in solution and trigger the sprouting of neurites.

Both the MIT and Northwestern researchers hope that these self-assembling nanoscaffolds might help damaged brain or neural tissue to regenerate, for example after spinal-column injuries. Such damage is problematic not only because it can be particularly debilitating but because there are several obstacles to the regrowth of the neural conduits (axons). Adult axons don't tend to grow back spontaneously; instead, such lesions create scar tissue. That is another reason why Stupp's peptide scaffolds, which suppressed the differentiation of neuron progenitor cells into scar-forming astrocytes, looked so appealing.

Ellis-Behnke and colleagues have now taken things a step further by demonstrating the regeneration of functional brain tissue in live animals. They made cuts in the part of the midbrain of hamsters that processes vision, rendering them sightless. In untreated animals, this lesion turned into scar tissue that prevented any regrowth, and the hamsters remained blind. But when Zhang's self-assembling peptides were injected into the wound region, the lesions healed within several weeks: the axons grew to close the gap, and the animals regained some sight. The peptide network, say the researchers, "appears to knit the tissue together".

They hope ultimately to conduct trials on humans who have suffered spinal-cord injuries.

http://www.nature.com/materials/nanozon ... 413-3.html

Interesting research from Rutledge Ellis-Behnke. Here are a couple of new abstracts on what he's been doing to fix our brains.


Nano neurology and the four P's of central nervous system regeneration: preserve, permit, promote, plasticity.

Med Clin North Am. 2007 Sep;91(5):937-62.
Ellis-Behnke R.
MIT, Brain and Cognitive Sciences, 46-6007, 43 Vassar Street, Cambridge, MA 02139, USA. rutledg@mit.edu

True nanomaterials are delivered as a specific structure, or combination of structures, designed to deliver the therapeutic intact, directly to the site, requiring a much lower dose. These materials use very specific and deliberate molecular structures that can interact with neurons or protein structures inside the cells. Until recently, functional recovery of the central nervous system (CNS) was an unattainable goal and nanotechnology was an invisible science. A well-planned treatment spaced over time will produce functional return in the CNS. The four P's of CNS regeneration is a new framework for approaching CNS injury and evidence shows that nanotechnology is currently being used for stroke rehabilitation and, in several clinical trials, the treatment of scar formation blockade in the spinal cord. The four components are preserve, permit, promote, and plasticity.

Pubmed link


Reknitting the injured spinal cord by self-assembling peptide nanofiber scaffold.

Nanomedicine. 2007 Dec;3(4):311-21. Epub 2007 Oct 26.
Guo J, Su H, Zeng Y, Liang YX, Wong WM, Ellis-Behnke RG, So KF, Wu W.
Department of Anatomy, The University of Hong Kong Li Ka Shing Faculty of Medicine, Pokfulam, Hong Kong SAR, China.

In traumatic spinal cord injury, loss of neurological function is due to the inability of damaged axons to regenerate across large, cystic cavities. It has recently been demonstrated that a self-assembled nanofiber scaffold (SAPNS) could repair the injured optical pathway and restore visual function. To demonstrate the possibility of using it to repair spinal cord injury, transplanted neural progenitor cells and Schwann cells were isolated from green fluorescent protein-transgenic rats, cultured within SAPNS, and then transplanted into the transected dorsal column of spinal cord of rats. Here we report the use of SAPNS to bridge the injured spinal cord of rats, demonstrating robust migration of host cells, growth of blood vessels, and axons into the scaffolds, indicating that SAPNS provides a true three-dimensional environment for the migration of living cells.

Pubmed link

Thanks for that, Dignan, I find this a fascinating area of research with huge potential. Nanotechnology seems to be bubbling along quietly, hardly noticed by anyone because we're all so focused on drug research, yet increasingly it comes up with amazing breakthroughs in the field of medicine which overcome previous stumbling blocks: for instance it could be used to transport therapeutic molecules across the blood brain barrier – one of the holy grails of neuroscience.
The prevention of scar tissue formation is crucial, but for an old-timer like me I'd love to see some way of breaking down or breaking through existing scarring.

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Dom

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Different researchers, but related to the nano-scaffold for neuroregeneration idea...


Promising new nanotechnology for spinal cord injury

CHICAGO -- A spinal cord injury often leads to permanent paralysis and loss of sensation below the site of the injury because the damaged nerve fibers can't regenerate. The nerve fibers or axons have the capacity to grow again, but don’t because they're blocked by scar tissue that develops around the injury.

Northwestern University researchers have shown that a new nano-engineered gel inhibits the formation of scar tissue at the injury site and enables the severed spinal cord fibers to regenerate and grow. The gel is injected as a liquid into the spinal cord and self -assembles into a scaffold that supports the new nerve fibers as they grow up and down the spinal cord, penetrating the site of the injury.

When the gel was injected into mice with a spinal cord injury, after six weeks the animals had a greatly enhanced ability to use their hind legs and walk.

The research is published today in the April 2 issue of the Journal of Neuroscience.

"We are very excited about this," said lead author John Kessler, M.D., Davee Professor of Stem Cell Biology at Northwestern University's Feinberg School of Medicine. "We can inject this without damaging the tissue. It has great potential for treating human beings."

Kessler stressed caution, however, in interpreting the results. "It's important to understand that something that works in mice will not necessarily work in human beings. At this point in time we have no information about whether this would work in human beings."

"There is no magic bullet or one single thing that solves the spinal cord injury, but this gives us a brand new technology to be able to think about treating this disorder," said Kessler, also the chair of the Davee Department of Neurology at the Feinberg School. "It could be used in combination with other technologies including stem cells, drugs or other kinds of interventions."

“We designed our self-assembling nanostructures -- the building blocks of the gel -- to promote neuron growth,” said co-author Samuel I. Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry, and Medicine and director of Northwestern’s Institute for BioNanotechnology in Medicine. “To actually see the regeneration of axons in the spinal cord after injury is a fascinating outcome.”

The nano-engineered gel works in several ways to support the regeneration of spinal cord nerve fibers. In addition to reducing the formation of scar tissue, it also instructs the stem cells --which would normally form scar tissue -- to instead to produce a helpful new cell that makes myelin. Myelin is a substance that sheaths the axons of the spinal cord to permit the rapid transmission of nerve impulses.

The gel's scaffolding also supports the growth of the axons in two critical directions -- up the spinal cord to the brain (the sensory axons) and down to the legs (the motor axons.) "Not everybody realizes you have to grow the fibers up the spinal cord so you can feel where the floor is. If you can't feel where the floor is with your feet, you can't walk," Kessler said.

Now Northwestern researchers are working on developing the nano-engineered gel to be acceptable as a pharmaceutical for the Food & Drug Administration.

If the gel is approved for humans, a clinical trial could begin in several years.

"It's a long way from helping a rodent to walk again and helping a human being walk again," Kessler stressed again. "People should never lose sight of that. But this is still exciting because it gives us a new technology for treating spinal cord injury."

http://www.eurekalert.org/pub_releases/ ... 040208.php

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If I've understood the article correctly, this technique inhibits the formation of scar tissue, but I can't see any mention of dissolving old, preexisting sclerosis.
Maybe I just can't see the screen properly because my wrinkled, haggard skin is sagging down over my eyes!
I do seem to remember mention of a molecule which does exactly that some time ago , but I can't put my finger on it now .

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Dom

Dom,
I think Acorda's Chondroitinase can enzymetically get rid of scars - of course, it's only preclinical.

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Thanks itsjustme, while researching Chondroitinase I found a number of things which inhibit neuronal growth such as NG 2, and substances which block their action, but I also found this which suggests that foetal stem cells may also perform the trick of dissolving scar tissue :


Bob, having studied human nature extensively through watching television, it is blindingly obvious that one twin is always evil, and it's usually the better looking one.

Which one do you want to be?

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Dom

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Dom, I'm not sure, is this the article you were thinking of that mentions something that could help with scar tissue?

http://www.thisisms.com/ftopict-4847.html

Dignan, I followed your link and read through the article, all the while thinking, " no, I've never seen this before – it must have been something else", only to scroll down and be confronted with my own smirking image alongside the reply I wrote! So this could be what I was thinking of… on the other hand… who knows?

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Dom

a little more on stem cell scaffolding

Stem cell 'scaffolding' examined

Stem cell "scaffolding" could help improve the lives of stroke patients, it has been announced.

New research is looking at anchoring stem cells on to special molecules to help regenerate damaged brain tissue.

The scientists behind the move hope their findings will one day lead to patients regaining some of the functions they lost after a stroke.

Strokes cause a temporary loss of blood supply to the brain, which results in areas of brain tissue dying off. This can then result in the loss of bodily functions such as speech and movement.

Neural stem cells can help tissue regeneration but scientists face major obstacles when trying to deliver these cells to the brain.

Now researchers have found a way to combine stem cells with microparticles - organic molecules called PGLA. These microparticles would act like "scaffolding", providing a structure for the cells to hook on to.

Researchers hope the scaffolding would make it easier for the cells to attach themselves to the cavities in the brain caused by strokes.

The structure would then hold the cells in place until they can connect with the surrounding healthy tissue. Once they have done their job, the particles would dissolve away.

Neurobiologists from the Institute of Psychiatry at King's College London and tissue engineers from the University of Nottingham are behind the research, aided by funding from the Biotechnology and Biological Sciences Research Council.

Dr Mike Modo from the Institute of Psychiatry will unveil his findings on the second day of the inaugural UK National Stem Cell Network conference in Edinburgh.