BSTP/STP Webinar: Pathology of Mice With Humanised Immune Systems
December 8, 2020
11:00 AM EST, 4:00 PM GMT/ 5:00 PM CET
A BSTP webinar - in collaboration with the Society of Toxicological Pathology (STP) to be held on Tuesday 8th December 2020, at 11:00 am Eastern Standard Time (New York, GMT-05:00), 4:00 pm GMT Time (London, GMT), and the duration of the webinar will be up to 1 hour.
The webinar will start with an introduction to some of the outstanding challenges and opportunities for using Human Immune System mice to investigate the human immune response in vivo. The second talk will focus on the histopathological features unique to NSG-SGM3 mice transplanted with human CD34+ hematopoietic stem cells.
Humanised Mouse Models: Challenges and Opportunities for Investigating the Human Immune Response
Kourosh Saeb-Parsy, PhD, MBChB
University of Cambridge
Definitive investigation of the human immune response in vivo is an essential step for the clinical translation of cellular and biological therapeutics. Mice reconstituted with a human immune compartments, knowns as Humanised or Human Immune System (HIS) mice, represent attractive experimental models. However, the engraftment and function of the human immune compartment in these models is typically incomplete. An increasingly wide range of HIS mouse models are therefore available to address these deficiencies. Understanding the limits and opportunities represented by each model is critical for ensuring generation of robust and reproducible data on the safety and efficacy of the therapies under investigation. This presentation reviews some of the outstanding challenges and opportunities for using HIS models to investigate the human immune response in vivo.
Myeloproliferation in Humanized NSG-SGM3 Mice
Laura Jean Janke, DVM, PhD, DACVP
St. Jude Children’s Research Hospital
Immunocompromised mouse strains expressing human transgenes are being increasingly used in biomedical research. The genetic modifications in these mice cause various cellular responses, resulting in histologic features unique to each strain. The NSG-SGM3 mouse strain is similar to the commonly used NSG (NOD scid gamma) strain but expresses human transgenes encoding stem cell factor (also known as KIT ligand), granulocyte-macrophage colony-stimulating factor, and interleukin 3. Three histopathologic features have been observed in these mice when they are unmanipulated or after transplantation with human CD34+ hematopoietic stem cells (HSCs). The first feature is mast cell hyperplasia: unmanipulated, naïve mice develop periductular pancreatic aggregates of murine mast cells, whereas mice given the hCD34+ HSCs develop a proliferative infiltrative interstitial pancreatic mast cell hyperplasia but with human mast cells. The second feature is the predisposition of NSG-SGM3 mice given these human cells to develop eosinophil hyperplasia. The third feature, secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)–like disease, is the most pronounced in both its clinical and histopathologic presentations. As part of this disease, a small number of mice also have histiocytic infiltration of the brain and spinal cord with subsequent neurologic or vestibular signs. The presence of any of these features can confound accurate histopathologic interpretation; therefore, it is important to recognize them as strain characteristics and to differentiate them from what may be experimentally induced in the model being studied.
We look forward to your participation.