How nano-medicine, stem cell therapy restore walking ability in rats
Scientists have demonstrated in two separate studies how nano-spheres injected into the blood shortly after an accident, and embryonic stem cell therapy restore walking ability in rats. The second study, which has received the United States Food and Drug Administration, FDA's approval supports expansion of first human trial to include those with cervical spinal cord damage. CHUKWUMA MUANYA reports.
UNITED States (U.S.) researchers have made progress in the search spinal injury repair. Using two different methods, the scientists have been able to restore walking ability after spinal injury in animal models.
According to a recent study published in the November 8 edition of journal Nature Nanotechnology, Purdue University, Indiana researchers have discovered a new approach for repairing damaged nerve fibres in spinal cord injuries using nano-spheres that could be injected into the blood shortly after an accident.
The synthetic "copolymer micelles" are drug-delivery spheres about 60 nanometres in diameter, or roughly 100 times smaller than the diameter of a red blood cell.
Also, the first human embryonic stem cell treatment approved by the United States Food and Drug Administration, FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries.
The results of the finding published in the journal Stem Cells could expand the clinical trial to include people with cervical damage.
Until now, researchers have been studying how to deliver drugs for cancer treatment and other therapies using these spheres. Medications might be harbored in the cores and ferried to diseased or damaged tissue.
Purdue University, Indiana researchers have now shown that the micelles themselves repair damaged axons, fibres that transmit electrical impulses in the spinal cord.
"That was a very surprising discovery," said Ji-Xin Cheng, an associate professor in the Weldon School of Biomedical Engineering and Department of Chemistry. "Micelles have been used for 30 years as drug-delivery vehicles in research, but no one has ever used them directly as a medicine."
In January, the FDA gave Geron Corp. of Menlo Park, California, permission to test the University of California Irvine (UCI) treatment in individuals with thoracic spinal cord injuries, which occur below the neck. However, trying it in those with cervical damage was not approved because preclinical testing with rats had not been completed.
UCI scientist Hans Keirstead hopes the data will prompt the FDA to authorise clinical testing of the treatment in people with both types of spinal cord damage. About 52 per cent of spinal cord injuries are cervical and 48 per cent thoracic.
A critical feature of micelles is that they combine two types of polymers, one being hydrophobic and the other hydrophilic, meaning they are either unable or able to mix with water. The hydrophobic core can be loaded with drugs to treat disease.
The micelles might be used instead of more conventional "membrane sealing agents," including polyethylene glycol, which makes up the outer shell of the micelles. Because of the nanoscale size and the polyethylene glycol shell of the micelles, they are not quickly filtered by the kidney or captured by the liver, enabling them to remain in the bloodstream long enough to circulate to damaged tissues.
In research led by biomedical engineering doctoral student Yunzhou Shi, the micelles also were shown to be non-toxic at the concentrations required. "With the micelles, you need only about 1/100,000th the concentration of regular polyethylene glycol," Cheng said.
Ongoing research at Purdue has shown the benefits of polyethylene glycol, or PEG, to treat animals with spinal cord injuries. The work is led by Richard Borgens, director of the Centre for Paralysis Research and the Mari Hulman George Professor of Neurology in the School of Veterinary Medicine.
Earlier findings have shown that PEG specifically targets damaged cells and seals the injured area, reducing further damage. It also helps restore cell function.
Keirstead, a primary author of the study said: "People with cervical damage often have lost or impaired limb movement and bowel, bladder or sexual function, and currently there's no effective treatment. It's a challenging existence.
"What our therapy did to injured rodents is phenomenal. If we see even a fraction of that benefit in humans, it will be nothing short of a home run."
A week after test rats with 100 per cent walking ability suffered neck spinal cord injuries, some received the stem cell treatment. The walking ability of those that didn't degraded to 38 percent. Treated rats' ability, however, was restored to 97 per cent.
UCI's therapy utilises human embryonic stem cells destined to become spinal cord cells called oligodendrocytes. These are the building blocks of myelin, the biological insulation for nerve fibers that's critical to proper functioning of the central nervous system. When myelin is stripped away through injury or disease, paralysis can occur.
Lead author and doctoral student Jason Sharp, Keirstead and colleagues discovered that the stem cells not only rebuilt myelin but prevented tissue death and triggered nerve fibre re-growth. They also suppressed the immune response, causing an increase in anti-inflammatory molecules.
The new findings by Purdue University researchers were made possible by the interdisciplinary nature of the work, Cheng said. The collaboration included Borgens; Riyi Shi, an associate professor of biomedical engineering and basic medical sciences; and Kinam Park, Showalter Distinguished Professor of Biomedical Engineering and a professor of pharmaceutics.
The findings showed that cores made of particular materials work better than others at restoring function to damaged axons, which are slender extensions of nerve cells.
The research also showed that without the micelles treatment about 18 per cent of axons recover in a segment of damaged spinal cord tested in a "double sucrose gap recording chamber." The micelles treatment boosted the axon recovery to about 60 per cent. The researchers used the chamber to study how well micelles repaired damaged nerve cells by measuring the "compound action potential," or the ability of a spinal cord to transmit signals.
The experiment mimics what happens during a traumatic spinal cord injury. Findings showed that micelles might be used to repair axon membranes damaged by compression injuries, a common type of spine injury.
The researchers also tracked dyed micelles in rats, demonstrating that the nanoparticles were successfully delivered to injury sites. Findings also showed micelles-treated animals recovered the coordinated control of all four limbs, whereas animals treated with conventional polyethylene glycol did not.
