Although previous attempts to re-create a single person's immune system in a mouse have largely failed, Columbia University Medical Center scientists say they've succeeded this time, using human bone marrow stem cells and HLA-matched immature thymus tissue, among other ingredients.
Their new finding, detailed in the online edition of Science Translational Medicine, offers potentially promising news to doctors seeking an ideal drug to treat a specific patient with Type 1 diabetes or another autoimmune disease. The Columbia team sees their "designer" mice as eventually coming in handy in all kinds of ways, making them potential "guinea pigs" on which to test existing drugs or therapies--even for diseases like cancer or other infections. The idea is to see which treatment works best and then to test it on the counterpart human patient. Initially, however, the researchers plan to use their enhanced, personalized mice to analyze any genetic abnormalities behind Type 1 diabetes. (A number of HLA-related genes appear connected to the disease, the researchers point out.)
"We hope to find out what is fundamentally different about patients' immune systems, compared with those of healthy individuals, before any disease develops," senior author Megan Sykes said in a statement.
This is a fascinating advance, because the successful duplication of a human immune system in mice opens all kinds of theoretical doors to safely testing drugs and treatments, both in development and on the market, without harming people. It's also a big advance toward personalized medicine to have a surrogate human immune system in mice on which to figure out which drug works best.
But the key word here is "theoretical." Though they've successfully transplanted the human immune system into a mouse, the scientists now have to see if treatments tested in the rodents will indeed work as well in people, and determine if they can decipher the secrets behind Type 1 diabetes using this method. In short, the practical use of mice with human immune systems for both research and treatment remains unproven.
Sykes and her team transplanted human bone marrow stem cells into mice bred to not have an immune system of their own. They also added a small amount of human leukocyte antigen (HLA)-matched immature thymus tissue into the rodents' kidney capsule (a membrane that wraps around the kidney). And then they waited. It takes between 6 and 8 weeks for the stem cells to circulate through the blood and seed the thymus tissue transplant, and then generate human immune cells. Other techniques including freezing and thawing the transplanted thymus tissue also helped, the researchers note.
- here's the release
- read the journal abstract