"Immune Mouse that Fully Recapitulates Individual Human Immune System Developed" in Genetic Engineering & Biotechnology NewsThursday, March 15, 2012
Scientists report on the development of a mouse model that recapitulates the immune system of a single adult human. In contrast with existing humanized mouse models with immune systems derived from transplanted fetal hematopoietic stem cells (HSCs), the immune system of the model described by the Massachusetts General Hospital and Columbia University Medical Center team is derived from a relatively few adult human HSCs. These could effectively be taken from any human volunteer or patient.
Megan Sykes, M.D., and colleagues, say the the resulting "personalized immune" (PI) mice generated a robust and diverse repertoire of fully functional T cells that were self-tolerant, and exhibited immune responses that mimicked those of the adult CD34+ cell donor. The team reports on its approach and initial analyses of a diabetic PI mice in Science Translational Medicine, in a paper titled “A Model for Personalized in Vivo Analysis of Human Immune Responsiveness.”
Read the full article here.
Science Translational Medicine paper, "A Model for Personalized in Vivo Analysis of Human Immune Responsiveness"Hannes Kalscheuer, Nichole Danzl, Takashi Onoe,Ted Faust, Robert Winchester, Robin Goland, Ellen Greenberg, Thomas R. Spitzer, David G. Savage, Hiroyuki Tahara, Goda Choi, Yong-Guang Yang, Megan SykesWednesday, March 14, 2012
Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies. Immunodeficient mice receiving human fetal thymus grafts and fetal CD34+ cells intravenously produce robust human immune systems, allowing analysis of human T cell development and function. However, to use humanized mice to study human immune-mediated disorders, immune systems must be generated from adult hematopoietic cells. Here, we demonstrated robust immune reconstitution in mice with hematopoietic stem cells (HSCs) aspirated from bone marrow of adults with type 1 diabetes (T1D) and healthy control volunteers. In these humanized mice, cryopreservation of human leukocyte antigen allele–matched fetal thymic tissue prevented allogeneic adult HSC rejection. Newly generated T cells, which included regulatory T cells (Tregs), were functional and self-tolerant and had a diverse repertoire. The immune recognition of these mice mimicked that of the adult CD34+ cell donor, but the T cell phenotypes were more predominantly “naïve” than those of the adult donors. HSCs from T1D and control donors generated similar numbers of natural Tregs intrathymically; however, peripheral T cells from T1D subjects showed increased proportions of activated or memory cells compared to controls, suggesting possible HSC-intrinsic differences in T cell homeostasis that might underlie immune pathology in T1D. This “personalized immune” mouse provides a new model for individualized analysis of human immune responses that may provide new insights into not only T1D but also other forms of immune function and dysfunction as well.
Columbia University Medical Center (CUMC) scientists have developed a way to recreate an individual's immune system in a mouse.Wednesday, March 14, 2012
Columbia University Medical Center (CUMC) scientists have developed a way to recreate an individual's immune system in a mouse. The "personalized immune mouse" offers researchers an unprecedented tool for individualized analysis of abnormalities that contribute to type 1 diabetes and other autoimmune diseases, starting at the onset of disease. The findings were published today in the online edition of Science Translational Medicine.
Read more here.
Dr. Megan Sykes featured in the Spring, 2011 edition of CUMC's P&S Magazine in "Reimagining Organ Transplantation", by Susan Conova.P&S Magazine, Spring 2011Thursday, August 4, 2011
Dr. Sykes discusses the CCTI's commitment to the strategy of preventing attacks on donated organs by the creation of a chimeric immune system within the transplant patient; one that is part donor and part recipient.
Anette Wu, MD, PhDFriday, July 1, 2011
Induction of Liver Allograft Tolerance through Bone Marrow Transplantation: Translational Preclinical Pilot Study in Monkeys
Nichole M. Danzl, PhDFriday, July 1, 2011
Cell intrinisc immunopathology of type 1 diabetes in a humanized mouse model
Hiroyuki Tahara MD, PhDFriday, July 1, 2011
There is a critical shortage of allogeneic organs. A more elegant, long-term solution is to use transplantation from other species. However, unresolved questions exsist concerning the susceptibility of xenografts to severe rejection and its mechanism.