July 14, 2003.
For the first time scientists have shown that brain stem cells are immune privileged, which means that they are invisible to a transplant recipient's immune system and do not trigger the immune system to reject them. These results, published in the July issue of Stem Cells, indicate that using central nervous system stem cells in transplants for diseases of the eye (which is part of the brain), brain, and spinal cord, may eliminate the need for tissue typing before, and immunosuppressive drugs after, transplantation. Ultimately these findings promise to improve the success of retinal transplantation to regenerate vision for millions with macular degeneration, retinitis pigmentosa and diabetic retinopathy and brain transplants to restore functioning for patients with disorders such as Parkinson's disease.
"These findings are very exciting," says Michael Young, PhD, the lead author of the study and an assistant scientist at Schepens Eye Research Institute and assistant professor at Harvard Medical School. "Though we suspected brain stem cells might be protected in this way, this is the first documented evidence."
Most tissues when transplanted from one body to another are seen by the recipient as foreign and attacked by the immune system. This is because the transplanted tissue has molecules on its surface called antigens that are recognized by the immune system as "not self." If the immune response goes unchecked by drugs to inhibit the attack, it will eventually destroy the transplanted tissue and reject it.
There are sites in the body that do not mount attacks against foreign tissue because to do so would be too self-destructive. For instance, in the eye an all out immune attack would cause inflammation that would destroy delicate tissue and, with it, vision. These sites, which are known as "immune privileged," include the eye, the brain, the digestive system, and the reproductive system.
Young, who in previous research found that brain and retinal stem cells transplanted into the eyes of mice and rats seemed to survive longer and integrate more easily into damaged retinas than other cells, suspected that these "neural stem cells" might be immune privileged. The only way for him to learn the true nature of their immune properties was to transplant these neural stem cells to a part of the recipients body that, unlike the eye, was not immune privileged already.
He and his colleagues chose a part of the body that always rejects transplanted tissue without immunosuppressant drugs and without close tissue typing – the kidney capsule, the pouch in which the kidney is located. This pouch is commonly used to determine whether transplants can survive. Over the years scientists have tested skin, cornea and other tissues in the kidney capsule to evaluate their transplant potential.
Young and his colleagues took brain stem cells from green mice (mice in which the gene for green protein found in jellyfish has been inserted) and placed them under the kidney capsule in other normal non-green mice. After 4 weeks, the team examined the mice and found that the stem cells had not been rejected in any of the mice, and, in fact, had grown into neural tissue.
They concluded that these neural stems cells did not induce an immune response and must be invisible to the immune system, at least initially. The next step was to determine if the cells possessed the antigens that most other tissues had. To test this theory, the team took other brain cells (not stem cells) from the green mice and implanted them in the normal non-green mice. These cells were rejected, and when brain stem cells were then again implanted in the normal non-green mice, they, too were rejected. The team concluded, therefore, that the brain stem cells did possess antigens, but unless the recipient was primed or pre-immunized, the antigens were not visible to the immune system of the recipient and not rejected.
"Understanding the immune properties of these stem cells could have an enormous effect on how we perform brain or retinal transplantations in the future. Stem cells already have the advantage of being able to transform or differentiate into various types of cells and can be reproduced endlessly outside the body. Now we know that at least brain stem cells are immune privileged and can be used without the same worry about tissue matching or immunosuppression that is true for other types of tissue. Young is the director of Schepens Eye Research Institute's Minda de Gunzburg Retinal Transplantation Research Center. The center is committed, with a focus on retinal regeneration, to unlocking the mysteries of vision and finding the cures for blinding eye diseases that devastate millions in the United States and around the world.
The study, titled "Neural progenitor cells lack immunogenicity and resist destruction as allografts" can be obtained at the Stems Cells website at http://stemcells.alphamedpress.org/ or by emailing firstname.lastname@example.org or email@example.com.
Other members of the research team include Junko Hori, Tat Fong Ng, Marie Shatos, and J. Wayne Streilein of Schepens Eye Research Institute of Boston and Henry Klassen of the Stem Cell Research Program at Children's Hospital of Orange County in Orange, California.
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