'Bionic' Nerve To Bring Damaged Limbs And Organs Back To Life

Source:

http://www.sciencedaily.com/releases/2007/10/071017094047.htm

Science Daily — University of Manchester researchers have transformed fat tissue stem cells into nerve cells - and now plan to develop an artificial nerve that will bring damaged limbs and organs back to life.

In a study published in October's Experimental Neurology, Dr Paul Kingham and his team at the UK Centre for Tissue Regeneration (UKCTR) isolated the stem cells from the fat tissue of adult animals and differentiated them into nerve cells to be used for repair and regeneration of injured nerves. They are now about to start a trial extracting stem cells from fat tissue of volunteer adult patients, in order to compare in the laboratory human and animal stem cells.
Following that, they will develop an artificial nerve constructed from a biodegradable polymer to transplant the differentiated stem cells. The biomaterial will be rolled up into a tube-like structure and inserted between the two ends of the cut nerve so that the regrowing nerve fibre can go through it from one end to the other.
This 'bionic' nerve could also be used in people who have suffered trauma injuries to their limbs or organs, cancer patients whose tumour surgery has affected a nearby nerve trunk and people who have had organ transplants.
With a clinical trial on the biomaterial about to be completed, the researchers hope the treatment could be ready for use in four or five years.
Dr Kingham said: "The differentiated stem cells have great potential for future clinical use, initially for treatment of patients with traumatic injuries of nerves in the arms and legs.
"This work will also help to develop a similar surgical approach for organ transplant, to give full functional recuperation to the transplanted tissue.
"Furthermore, the technique of artificial nerve grafting could also be applicable when tumour mass has involved a nearby nerve trunk, which consequently has to be excised together with the tumour, such as the removal of a prostate tumour where damage to the nerve leads to male impotence."
Director of the UKCTR, Professor Giorgio Terenghi said: "This new research is a very exciting development with many future clinical applications that will improve the lives of many different types of patients and therefore many, many people.
"The frequency of nerve injury is one in every 1,000 of the population - or 50,000 cases in the UK - every year.
"The current repair method - a patient donating their own nerve graft to span the gap at the injury site - is far from optimal because of the poor functional outcome, the extra damage and the possibility of forming scars and tumours at the donor site. Tissue engineering using a combination of biomaterials and cell-based therapies, while at an early stage, promises a great improvement on that. Artificial nerve guides provide mechanical support, protect the re-growing nerve and contain growth factor and molecules favourable to regeneration. The patient will not be able to tell that they had ever 'lost' their limb and will be able carry on exactly as they did before."
He added: "The facilities available at the UKCTR have been developed jointly by the University of Manchester and the North West Development Agency, with exactly this aim - to provide the transition from experimental research to new clinical treatment."
Note: This story has been adapted from material provided by University of Manchester.

Fausto Intilla

www.oloscience.com

New View Of DNA Repair: Enzyme Alerts Cell's Powerful Army To Repair DNA Damage

Source:

http://www.sciencedaily.com/releases/2007/09/070905173151.htm

Science Daily — Scientists know that inside each cell, a little engine called RNA polymerase II does one essential job: It copies instructions from genes in the nucleus that get carried to production units in the rest of the cell to support our daily needs. Now researchers at the University of Michigan Medical School have shown that RNA polymerase II also constantly scans the cell's DNA for damage. When certain types of damage in DNA halt the action of RNA polymerase II, a stress signal is generated that alerts a key tumor-suppressor protein called p53.

The activities of p53, a master protein that responds to DNA damage by marshaling hundreds of genes to repair or eliminate damaged cells, have been the subject of thousands of studies. Mutations in the p53 gene occur in more than half of all cancers.
"We have come up with a new paradigm for how cells protect themselves against cancer-producing DNA lesions," says Mats Ljungman, Ph.D., a U-M researcher and lead author of a recent study in the Proceedings of the National Academy of Sciences.
"Much is known already about p53, but this adds a significant piece of knowledge about how it is activated," Ljungman adds. He is an associate professor in the Department of Radiation Oncology in the Division of Radiation and Cancer Biology at the U-M Comprehensive Cancer Center and associate professor of Environmental Health Sciences at the U-M School of Public Health.
A commentary in the journal praised the U-M study and urged more attention to RNA polymerases as major sensors "for all DNA damage response reactions."
Ljungman says the findings have implications for the study of cancer, aging and neurological diseases. Figuring out precisely how cells detect and repair damage is crucial in understanding what goes wrong in cancer, in which harmful mutations can elude the body's ability to control cell division.
Finding and repairing DNA lesions is a non-stop job for cells.
As many as 20,000 lesions occur daily in a cell's DNA, Ljungman says. Many stresses result from oxidation and other internal cell processes. In addition, our DNA is also challenged by sunlight, radiation and reactive chemicals found in food.
"So much damage happens all the time," Ljungman says. "That puts pressure on cells to efficiently scan the DNA and do something about it. That's what we think the transcription machinery is doing."
RNA polymerase II is the main enzyme involved in transcription, the process of reading the genetic code. The U-M team did a series of experiments to find out what happens when transcription is blocked. They found that using transcription-blocking agents such as ultraviolet light resulted in activation of the p53 stress response, independent of other cell processes.
When they micro-injected an anti-RNA polymerase agent into human cell nuclei, they found that p53 proteins then accumulated in the cell nucleus -- one aspect of the stress response -- even when no DNA damage occurred. Ljungman and his colleagues also discovered what happens when RNA polymerase II gets stuck on a kink or other lesion in the DNA. It sends a signal via two proteins that activate p53.
"These two proteins are saying, 'Transcription has stopped,'" says Ljungman. These early triggers act like the citizen who smells smoke and sounds a fire alarm, alerting the fire department. Then p53, like a team of fire fighters, arrives and evaluates what to do. To reduce the chance of harmful mutations that may result from DNA damage, p53 may kill cells or stop them temporarily from dividing, so that there is time for DNA repair.
Learning more about the processes involved in transcription could pay off in improved treatments in years to come. Cisplatin, a drug used to treat testicular and ovarian cancer, acts by stopping transcription and causing cells to die. Some other chemotherapy drugs block transcription too. But these types of drugs also damage a cancer patient's DNA in normal tissues, sometimes leading to other cancers later.
The study's findings eventually could lead to better drugs that might target transcription directly without those ill effects, Ljungman believes.
In addition to Ljungman, other authors who worked on the U-M study include graduate students Frederick A. Derheimer, Heather M. O'Hagan, Heather M. Krueger, and Sheela Hanasoge, and Research Associate Michelle T. Paulsen, all from the Department of Radiation Oncology, Division of Radiation and Cancer Biology, U-M Comprehensive Cancer Center.
The study was funded by the National Institutes of Health, the University of Michigan and the Department of Radiation Biology.
Citation: Proceedings of the National Academy of Sciences, July 31, 2007, vol. 104, no. 31, 12778--12783
Note: This story has been adapted from a news release issued by University of Michigan Health System.

Fausto Intilla

www.oloscience.com