Tuesday, April 24, 2012

Bone Marrow May Hold Key to Stem Cell Breakthrough

PATIENTS suffering from spinal cord injury may soon find help in the form of stem cells drawn from their own bone marrow, thanks to a research project from the University of Western Australia.

UWA Associate Professor Stuart Hodgetts and PhD student Sarah Lovett are using human bone marrow stem cells (BMSCs) to promote an endogenous host response after spinal cord injury (SCI), by isolating stromal cells found in a patient’s own bone marrow and transplanting them back into the injury site in animal models.

A/Prof Hodgetts says the objective is to transplant these multipotent stromal stem cells into the spinal cord to promote the survival of existing neurons and improve repair at the injury site.

“We believe the donor BMSCs are responsible for producing an endogenous repair mechanism, essentially providing factors to help the host system repair itself. Our animal models have shown BMSCs promote good functional improvement beyond many other cell types used over the last 5–10 years,” he says.

Ms Lovett says the research does not specifically aim to differentiate BMSCs into neurons or supportive glial cells, but instead reduce the amount of secondary damage that occurs after the initial injury.

“We found BMSCs reduce inflammation in the injury site as well as reduce secondary damage. Also, while extracting cells from bone marrow might be regarded as an invasive procedure, it’s actually quite routine,” she says.

“If you can take bone marrow from an injured patient, after about 3 weeks’ culture you would have enough cells to transplant back into that person.”

Ms Lovett uses a contusion model in rats that best replicates the most common SCI in humans.

“The animals show good functional recovery if BMSCs are transplanted into the cord a week after injury. However, BMSCs are soon destroyed by the animal’s immune response against them,” she says.

Prof Hodgetts says part of the research is to modulate the immune response by inhibiting “TNF-alpha” molecules and “natural killer”, immune cells that may target the transplanted cells.

“Interestingly, within that window of four weeks, BMSCs are able to induce a response that markedly improves the locomotory ability of these animals.”

“If we can improve BMSC survival, we may be able to get them to further improve functional recovery for longer,” he says.

Prof Hodgetts’ Fellowship and this SCI research project is funded by the Neurotrauma Research Program of Western Australia.

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New Technique May Help Severely Damaged Nerves Regrow and Restore Function

Engineers at the University of Sheffield have developed a method of assisting nerves damaged by traumatic accidents to repair naturally, which could improve the chances of restoring sensation and movement in injured limbs.

In a collaborative study with Laser Zentrum Hannover (Germany) published April 23, 2012 in the journal Biofabrication, the team describes a new method for making medical devices called nerve guidance conduits or NGCs.

The method is based on laser direct writing, which enables the fabrication of complex structures from computer files via the use of CAD/CAM (computer aided design/manufacturing), and has allowed the research team to manufacture NGCs with designs that are far more advanced than previously possible.

Currently patients with severe traumatic nerve damage suffer a devastating loss of sensation and/or movement in the affected limb. The traditional course of action, where possible, is to surgically suture or graft the nerve endings together. However, reconstructive surgery often does not result in complete recovery.

"When nerves in the arms or legs are injured they have the ability to re-grow, unlike in the spinal cord; however, they need assistance to do this," said University of Sheffield Professor of Bioengineering, John Haycock. "We are designing scaffold implants that can bridge an injury site and provide a range of physical and chemical cues for stimulating this regrowth."

The new conduit is made from a biodegradable synthetic polymer material based on polylactic acid and has been designed to guide damaged nerves to re-grow through a number of small channels.

"Nerves aren't just like one long cable, they're made up of lots of small cables, similar to how an electrical wire is constructed," said lead author Dr Frederik Claeyssens, of the University's Department of Materials Science and Engineering. "Using our new technique we can make a conduit with individual strands so the nerve fibres can form a similar structure to an undamaged nerve."

Once the nerve is fully regrown, the conduit biodegrades naturally. The team hopes that this approach will significantly increase recovery for a wide range of peripheral nerve injuries.

In laboratory experiments, nerve cells added to the polymer conduit grew naturally within its channelled structure and the research team is now working towards clinical trials.

"If successful we anticipate these scaffolds will not just be applicable to peripheral nerve injury, but could also be developed for other types of nerve damage too. The technique of laser direct writing may ultimately allow production of scaffolds that could help in the treatment of spinal cord injury" said Dr Claeyssens.

"What's exciting about this work is that not only have we designed a new method for making nerve guide scaffolds which support nerve growth, we´ve also developed a method of easily reproducing them through micromolding.

"This technology could make a huge difference to patients suffering severe nerve damage," he added. This research was funded by the Engineering and Physical Sciences Research Council.

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