Grafting of human spinal stem cells into ALS rats best with immunosuppressant combination

December 19, 2011

A team of researchers grafting human spinal stem cells into rats modeled with amyotrophic lateral sclerosis (ALS), also known as "Lou Gehrig's Disease," a degenerative, lethal, neuromuscular disease, have tested four different immunosuppressive protocols aimed at determining which regimen improved long-term therapeutic effects. Their study demonstrated that a combined, systematically delivered immunosuppression regimen of two drugs significantly improved the survival of the human spinal stem cells. Their results are published in the current issue of Cell Transplantation (20:8), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"There are no therapeutic strategies that successfully modify ALS progression or outcome," said study corresponding author Dr. Michael P. Hefferan of the University of California-San Diego Neurodegeneration Laboratory. "Cell-based transplantation therapies have emerged as potential treatments for several neurological disorders, including ALS. However, cell graft survival seems to greatly depend on an accompanying immunosuppression regimen, yet there are differential responses to identical immunosuppressive therapies."

While the reason for this differential response is unclear, the study authors suggest that several mechanisms, including distinct types of acute and inflammatory responses, may be to blame.

Their study aimed at optimizing an immunosuppressive protocol for transplanting human into presymptomatic ALS G93A rats with the G93A superoxide dismutase (SOD1) mutation. Two drugs, tacrolimus (FK506) and mycophenolate, were used alone and in combination.

"Although FK506 has been used successfully as monotherapy in our previous studies of spinal ischemia, it failed in the present study on ALS," explained Dr. Hefferan, who speculated that inflammation played a role in the failure. "In contrast to ALS, where spinal inflammation continues and likely worsens until endstage, the traumatically-injured spinal cord is typically characterized by an acute inflammatory phase followed by a progressive loss of most inflammatory markers."

According to the researchers, the animals receiving combined immunosuppression of both FK506 and mycophenolate likely benefited from the longer half-life of mycophenolate rather than from its action.

"The addition of mycophenolate seemed to supplement inhibition of T-cell formation and led to a robust when analyzed three weeks after grafting," concluded Dr. Hefferan.

Explore further: Potential new drug target in Lou Gehrig's disease

More information: Hefferan, M. P.; Johe, K.; Hazel, T.; Feldman, E. L.; Lunn, J. S.; Marsala, M. Optimization of Immunosuppressive Therapy for Spinal Grafting of Human Spinal Stem Cells in a Rat Model of ALS Cell Transplant. 20(8):1153-1161; 2011.

Provided by: Cell Transplantation Center of Excellence for Aging and Brain Repair

shares

Related Stories

Potential new drug target in Lou Gehrig's disease

November 14, 2011
Two proteins conspire to promote a lethal neurological disease, according to a study published online this week in the Journal of Experimental Medicine.

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.