EXPERIMENTAL DESIGN SUPPORT
The Translational Research Networking and Preclinical Models (TRNPM) Shared Resource aims to provide a nexus for multiple aspects of translational immunology research. The TRNPM 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 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 (see iLabs request form or contact Roberta Pelanda or Julie Lang).
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 lymph tissue.
Please contact Julie Lang (Julie.Lang@ucdenver.edu) or Roberta Pelanda (Roberta.Pelanda@ucdenver.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@ucdenver.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 TRNPM will provide this key component with the production, distribution and/or analysis of humanized mice. Humanized mice are immunodeficient mice transplanted with a human immune system, or some of its components. Humanized 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 humanized mice become an ideal tool for testing the effects of novel immunotherapies, such as immune checkpoint inhibitors, on human immune responses to tumors.
BRGS: BALB/c Rag2-/- IL2Rγ-/- SIRPα NOD mice
CD34-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, > 15 weeks.
Hu-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.
Hu-CBMC BRGS: Immunodeficient mouse humanized by injection with human cord blood (CB) mononuclear cells (MCs).
CD34-FLT-BRGS: COMING SOON!
Immunodeficient mouse humanized by using CD34+ fetal liver (FL) hematopoietic stem cells (HSC) and co-implantation of matched thymus. Humanized mice are verified for >25% human chimerism in blood.
CD34-BM-BRGS: COMING SOON!
Immunodeficient mouse humanized by using CD34+ bone marrow (BM) hematopoietic stem cells (HSC) at birth. Humanized mice are verified for >25% 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.
Humanized 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 for infection). Typically, this includes preparing single cell suspensions for flow cytometry and, can include additional services, such as freezing sections for histology or 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, T regulatory cells, B cells, plasmablasts, dendritic cells, monocytes, myeloid cells, MDSCs and IFNγ secreting cells. There are options for customization.
ELISA: Enzyme-Linked Immunosorbent Assays designed to measure human proteins in the sera of humanized mice without cross-reactivity with mouse proteins.