The Pre-clinical Human Immune System Mice Shared Resource (PHISM) aims to provide a nexus for multiple aspects of translational immunology research. The PHISM core intends to enable and promote collaboration among investigators along the continuum of basic-translational-clinical research by establishing mechanisms that facilitate availability of human tissue for research and by generating and maintaining preclinical “humanized” mouse models for the development and testing of candidate therapeutics.
To better serve our campus, we offer free initial project consultation regarding a high-level overview of experimental design, timeline, and associated analyses and services.
Initial project support: to discuss research project needs, a high-level overview of experimental design and timeline, and associated analyses and services (contact Julie Lang or Roberta Pelanda or see iLabs request form).
Experimental design support: planning beyond initial experimental design support to outline the details of the experiment(s) including number of mice, treatments, time-course and flow cytometry panel design for analysis of humanized mouse ltissue.
Please contact Julie Lang (Julie.Lang@cuanschutz.edu) or Roberta Pelanda (Roberta.Pelanda@cuanschutz.edu) for more details.
A goal of the HI3 is to foster relationships across disciplines to better leverage our human sample resources. Please contact Aimee Bernard (Aimee.Bernard@cuanschutz.edu) to learn how you can contribute to this effort and to add to our growing list of research needs.
Novel immunotherapies must be tested with sophisticated preclinical models before they can be tried in humans. Ideally, these models should provide a platform where the human immune system can be exposed to experimental and therapeutic manipulations and the readout is meaningful and applicable to humans.
The PHISM will provide this key component with the production, distribution and/or analysis of Human Immune System mice. Human Immune System mice are immunodeficient mice transplanted with a human immune system, or some of its components. Human Immune System mice can be utilized to understand basic mechanisms of the human immune system and to study genetic, biological, and pharmacological therapies to autoimmune and inflammatory responses. When also engrafted with tumors, these Human Immune System mice become an ideal tool for testing the effects of novel immunotherapies, such as immune checkpoint inhibitors, on human immune responses to tumors.
For additional details on the mice listed below, please see the ‘Rates and Fee Structure’ page of this website.
BRGS: BALB/c Rag2-/- IL2Rγ-/- SIRPαNOD mice
Highly immunodeficient mice (no T, B, NK cells) that can be engrafted with human immune systems and/or human tumor allografts.
HIS-CB-BRGS: Immunodeficient mouse generated from CD34+ hematopoietic stem cells (HSCs) from cord blood (CB) at birth and verified by two bleeds to be >25% human, > 14 weeks.
HIS-PBMC-BRGS: Immunodeficient mouse generated from peripheral blood mononuclear cells (PBMCs) from adult blood or cord blood (CB) and injected into adult BRGS immunodeficient mice. These mice can be used in short-term Cytokine Release Syndrome Assays, as described in https://doi.org/10.1096/fj.202001203R.
NBSGW: NBSGW (NOD.CgKitW41J Tyr + Prkdcscid Il2rgtm1Wjl/ThomJ)
NOD mice harboring a mutation in the stem cell related cKit gene that leads to reduced production of the mouse myeloid lineage.
HIS-CB-NBSGW: Coming Soon!
Humanized mice generated from CD34+ hematopoietic stem cells (HSCs) from cord blood (CB) at birth and verified by two bleeds to be >25% human, > 14 weeks. We are currently verifying the improved myeloid lineage.
HIS-PBMC-NBSGW: Coming Soon!
Humanized mouse generated from peripheral blood mononuclear cells (PBMCs) from adult blood or cord blood (CB) and injected into adult NBSGW immunodeficient mice.
NSGS, HIS-CB-NSGS, HIS-PBMC-NSGS: (NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ)
NOD mice with transgenic expression of myeloid-lineage specific cytokines. The HIS-mice generated from these mice have improved human myeloid engraftment.
HIS-FLT-BRGS: Humanized mouse generated by using CD34+ fetal liver (FL) hematopoietic stem cells (HSC) and co-implantation of matched thymus into BRGS. Humanized mice are verified for >25% human chimerism in blood.
HIS-BM-BRGS: Humanized mouse generated by using CD34+ bone marrow (BM) of mobilized blood hematopoietic stem cells (HSC), allowing personalized HIS-mice (from known donor). Humanized mice are verified for >5% human chimerism in blood.
SERVICES and ANALYSES
For additional details on the services and analyses listed below, please see the ‘Rates and Fee Structure’ page of this website.
Human Immune System mouse tissue harvest: Harvest of lymph tissue, including lymph nodes, spleen, bone marrow, thymus, blood and/or sera, and tumors or other organs of interest (e.g. liver, lung or gut). Typically, this includes preparing single cell suspensions for flow cytometry and, can include additional services, such as fixing sections for histology or freezing tissue for downstream RNA preparation.
Flow cytometry and analysis: Cell staining with pre-designed antibody panels to distinguish human lymphocyte and monocyte cells, their activation and functional status. This panel typically includes staining for CD4 and CD8 T cells including their activated/exhausted state (HLA-DR, PD-1, TIGIT, TIM-3, Granzyme B, IFNg and TNFa), T regulatory cells, B cells, NK cells, and myeloid cells (monocytes, macrophages and dendritic cells). Panels are inherently flexible and customizable.
ELISA: Enzyme-Linked Immunosorbent Assays designed to measure human proteins in the sera of Human Immune System mice without cross-reactivity to mouse proteins.
CB Isolation: Isolation of CD34+ Stem cells from CB.
Julie Lang, PhD
Assistant Director, Human Immune System Mouse Core