Laboratory mice have made valuable contributions to biological research for centuries, at first as a model to study broad questions such as blood circulation and respiration, and then, increasingly to home in on more-specific questions in health and medicine. In particular, researchers hit on the idea in the 1980s to replace a mouse’s immune system with that of a human’s.
These “humanized” mice have been useful models in some situations, such as the study of the human immune response to HIV infection or the transplantation of certain types of tissue. But recent research by cardiologist and stem cell expert Joseph Wu, MD, PhD, together with former postdoctoral scholars Nigel Kooreman, MD, and Patricia de Almeida, PhD, and graduate student Jonathan Stack, DVM, suggest that these mice don’t adequately mimic the human immune response to stem cell transplantation.
…the Stanford researchers found that, unlike what would occur in a human patient, the humanized mice are unable to robustly reject the transplantation of genetically mismatched human stem cells. As a result, they can’t be used to study the immunosuppressive drugs that patients will likely require after transplant. The researchers conclude that the humanized mouse model is not suitable for studying the human immune response to transplanted stem cells or cells derived from them.
The researchers also collaborated with Dale Greiner, PhD, from the University of Massachusetts Medical School, and Leonard Shultz, PhD, from the Jackson Laboratory. Greiner and Shultz helped to pioneer the use of humanized mice in the 1990s to model human diseases and they provided the mice used in the study.
Wu and his colleagues caution against using the current humanized mice as models for human stem cell transplantation, and urge the development of optimized models for use in clinical decision-making.
“Many in the fields of pluripotent stem cell research and regenerative medicine are pushing the use of the humanized mice to study the human immune response. But if we start to make claims using this model, assuming that these cells won’t be rejected by patients, it could be worrisome,” Kooreman said. “Our work clearly shows that, although there is some human immune cell activity, these animals don’t fully reconstitute the human immune system.”
Previously: When mice mislead, medical research lands in the trap, Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidates behavior in humans and Stroke of luck: Stem cell transplants show strong signs of efficacy in clinical safety trial for stroke
Photo by Jakub Solovsky