The approach breaks new ground in the field of biomedicine because it requires no gene therapy; can be administered after an injury has occurred and even after the wound has healed over; and is bioelectric, rather than chemically based.
In a paper appearing as the cover story of the September 29, 2010, issue of the Journal of Neuroscience, the Tufts team reported that a localized increase in sodium ions was necessary for young Xenopus laevis tadpoles to regenerate their tails – complex appendages containing spinal cord, muscle and other tissue.
* the frog tail could be induced to regenerate as late as 18 hours after amputation, revealing that tissues normally fated for regenerative failure still maintain their intrinsic characteristics and can be programmed to reactivate regeneration.
* The frog tail is a good model for human regeneration because it repairs injury in the same way that people do: each tissue makes more of itself.
The findings have tremendous implications for treating wounds sustained in war as well as accidental injuries. The treatment method used is most directly applicable to spinal cord repair and limb loss, which are highly significant medical problems world-wide. It also demonstrates a proof-of-principle that may be applicable to many complex organs and tissues.
“We have significantly extended the effective treatment window, demonstrating that even after scar-like wound covering begins to form, control of physiological signals can still induce regeneration. Artificially causing an influx of sodium for just one hour can overcome a variety of problems, such as the decline in regenerative ability that comes with age and the effect of regeneration-blocking drugs,” said Tufts Professor of Biology Michael Levin, Ph.D., corresponding author on the paper and director of the Center for Regenerative and Developmental Biology at Tufts. Co-authors were Research Associate Ai-Sun Tseng, Postdoctoral Associate Wendy S. Beane, Research Associate Joan M. Lemire, and Alessio Masi, a former post-doctoral associate in Levin’s laboratory.
The transport of ions in and out of cells is regulated by electronic security doors, or gates, that let in specific ions under certain circumstances. A role for sodium current in tissue regeneration had been proposed in the past, but this is the first time the molecular-genetic basis of the ion flow has been identified, and a specific drug-based treatment demonstrated. Until now, advances in this model system had involved administering therapies before the injury was sustained.
“This is a novel, biomedically-relevant approach to inducing regeneration of a complex appendage,” noted Levin.
The Tufts research established a novel role in regeneration for the sodium channel Nav1.2, a crucial component of nerve and cardiac function. It showed that local, early increase in intracellular sodium is required for initiating regeneration following Xenopus tail amputation, while molecular and pharmacological inhibition of sodium transport causes regenerative failure. The new treatment induced regeneration only of correctly-sized and patterned tail structures and did not generate ectopic or other abnormal growth
2. EU has a 3.2 million euro project that aims to induce the self healing capacity of damaged cartilage and bone by coordinated cooperation/interaction of gene vectors, mesenchymal stem cells, polymers and magnetic nanoparticles.
Degenerative Arthritis affects approximately every fourth German. Looking at the population aged 65 and higher every second person suffers from the disease, with increasing degeneration of cartilage and ultimately destruction of the underlying bone as well. The etiology of osteoarthritis (OA) is still unknown. Therapy is currently mainly symptomatic with reduction of pain and inflammation, but not restorative, and is often ending in total joint replacement. The newly started research project GAMBA (Gene Activated Matrices for Bone and Cartilage Regeneration in Arthritis) is investigating new methods to induce regenerative processes within the body
“GAMBA combines different aspects of osteoarthritis therapy in a unique fashion“ explains Dr. Martina Anton. Theses new strategies will be developed experimentally in the next three years. Researchers aim at inducing self-healing capacity of patients by use of mesenchymal stem cells (precursors for bone, cartilage and adipose tissue cells). Using gene vectors cells will be equipped with new genetic information that will allow for production of therapeutically relevant proteins in a transiently. Ideally a three-fold combination will be developed addressing inflammation as well as cartilage and bone repair. To achieve this researchers will use interleukin-10 for reduction of inflammation, BMP-2 (bone morphogenetic protein) for regeneration of bone and TGF-ß (transforming growth factor) for regeneration of cartilage. The reading of these genetic codes will be started and regulated from the outside by chemical and physical cues
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