October 4, 2012
Humanized Mice May Aid In Arthritis Research
Michael Harper for redOrbit.com — Your Universe Online
Rheumatoid arthritis research has just had an advance as scientists from the Northwestern University Feinberg School of Medicine have finally found an animal which has the same response to the disease as people: Humanized mice. This discovery will improve arthritis research, giving scientists an accurate model with which to try new drugs and procedures in an effort to treat and cure the disease.
The research team, lead by senior author Harris Perlman, associate professor of rheumatology at Feinberg have now explained their methods in a recent issue of the Journal of Translational Medicine, an online publication.
In a press release heralding this new breakthrough, Perlman explains the importance of being able to run rheumatoid arthritis tests on these model mice.
“This is the first time human stem cells have been transplanted into mice in order to find RA treatments,” says Perlman. “We believe this will improve drug discovery because the reactions we observed were authentic human reactions.”
Scientists studying RA have long had to perform such tests and research on specially bred mice. The problem with this method, according to the research team, is the significant difference between the immune systems of mice and humans. While some drugs may be successful at treating RA in mice, the same medications are likely to have different effects on humans, leaving a large margin for error in their testing, and as science is a precision game, this form of testing was not seen as entirely reliable. In order to rectify this difference and bridge the gap between these two immune systems, Perlman and his team implanted their mice with human stem cells just before testing. The practice of implanting these stem cells in mice is nothing new, of course, though these humanized mice have mostly been used to test the effects of infectious diseases.
Just before testing, Perlman´s team injected day-old mice with stem cells from the blood of the umbilical cord, including human white blood cells. These white blood cells are important to the research, as they regulate human immunity, therefore making the two immune systems more alike.
Once injected with stem cells, Perlman and colleagues subjected these mice to RA, followed by an injection of the drug Enbrel. This drug is commonly used as the first treatment in humans which reduces joint inflammation.
RA is a complex disease, capable of creating different molecular subtypes and affecting different parts of the body. Now, with a humanized model, these scientists are able to track the progression of the disease as well as study a close representation of how the human immune system reacts to the different types of RA. According to the press release, some 1.3 million people have RA, a debilitating disease which causes inflammation of the joints and can lead to pain, stiffness, swelling and even tissue destruction.
Though a feat in and of itself, this isn´t the first time Perlman has used a humanized mouse to study the effects of RA. His first mouse model could develop RA and was predisposed to a hardening of the arteries called atherosclerosis. This symptom is common in humans with the disease. Perlman calls this first mouse model the “tip of the iceberg” in terms of RA research and treatment. In the future, he hopes his research will expand to make use of stem cells from mothers who have the disease, therefore allowing him to work directly with the genetic makeup of RA directly.