Early Research Shows Stem Cells Can Improve Movement in Paralysed Rat
Just a decade ago, neuroscience textbooks held that neurons in the adult human brain and spinal cord could not regenerate. Once dead, it was thought, central nervous system neurons were gone. Because rebuilding nervous tissue seemed out of the question, research focused almost entirely on therapeutic approaches to relieve symptoms and limit further damage.
However, researchers at Johns Hopkins University recently reported preliminary evidence that cells derived from embryonic stem cells can restore movement in an animal model of amyotropic leteral sclerosis (ALS). It a rapidly progressive disorder destroys special nerves found in spinal cord known as motor neurons. Motor neurons are nerve cells that serve as controlling units and vital communication links between the nervous system and the voluntary muscle of the body. In ALS this motor neuron are degenerate or die, ceasing to send messages to muscles. Eventually, all muscles under voluntary control are affected, and patients lose their strength and the ability to move their arms, legs, and body which ultimately lead to paralysis. When muscles in the diaphragm, and chest wall fail, patients lose the ability to breathe by themselves, need to depend on ventilator support. Most people with ALS die from respiratory failure, usually within 3-5 years from the onset of symptoms. This cause is largely unknown, and there are no effective treatments.
In this study, the researchers used a mice model of ALS to test for possible nerves cell-restoring properties of stem cells. The rats were exposed to Neuroadaped Sindbis virus (NSV), single stranded RNA virus that specifically infects the central nervous system and destroys the motor neurons in the spinal cord. Rats that survive are left with paralysed muscles in their hindquarters and weakened back limbs. Scientists assess the degree of impairment by measuring the rats movement, quantifying electrical activity in the nerves serving the back limbs, and visually judging extend of nerve damage through a microscope.
The researchers wanted to see whether the stem cells could restore nerves and improve mobility in rats. Because scientists have had difficultly sustaining stem cell lines derived from rat embryos, the investigators conducted their experiments with embryonic germ cells isolated from human fetal tissue. These cells can produce unchanged copies of themselves when maintained in culture, and they form into clumps called embryoid bodies. Under certain conditions, research has shown that the cells in the embryoid bodies begin to look and function like neurons when subjected to specific laboratory conditions. The researchers had an idea that these embryotid body cells in their nonspecialized stage might become specialised as replacement neurons if placed into the area of the damaged spinal cord. So they carefully prepared cells from the embryoid bodies and injected them into the paralysed rats that had their motor neurons destroyed by the NSV.
To test this idea, the researchers selected from laboratory culture dishes barely differentiated embryonic germs cells that displayed the molecular markers of neural stem cells, including the proteins nestin and neuron specific enolase. They grew these cells in large quantities and injected them into the fluid surrounding the spinal cords of partially
Figure1. Neuroadapted Sindbis virus causes progressive lower motor neuron in rats. A, progressive kyphoscoliosis (left) and then hind limb paralysis (right) develop in rats after intracranial of 1000 pFU of rat-adapted Sindbis virus (raNSV)
paralysed, Sindbis-virus –rats.
The response was impressive. Three months of after the injections, many of the treated rats were able to move their hind limbs and walk, while the control rats that did not receive cell injections remains paralysed. Moreover, at autopsy the researchers found that cells derived from human embryonic germ cells had migrated throughout the spinal fluid and continued to develop, displaying both the shape and molecular markers characteristic of mature motor neurons. The researchers are quick to caution that their results are preliminary, and that they do not know for certain whether the treatment helped the paralysed rats because new neurons took the place of the old, or because trophic factors from the injected cells facilitated the recovery of the rat’s remaining nerve cells and helped the rats improve in their ability to use their hind limbs. Nor do they know how well this strategy will translate into a therapy for human neurodegenerative disease like ALS. And they emphasize that there are many hurdles to cross over before the use of stem cells to repair damaged motor neurons in patients can be considered. However, researchers are very excited about their results, which, if confirmed, would represent a major step toward using specialized stem cells from embryonic and fetal tissues sources to restore nervous functions.
1.Kerr, D.A., Llado, J., Shamblott, M., Maragakis, N., Irani, D.N., Dike, S., Sappington, A.,Gearhart, J., and Rothstein, J. (2006), Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury