Table 2 SCID Mouse and NOD/SCID mouse-based chimeric human models
From: Summary of presentations at the NIH/NIAID New Humanized Rodent Models 2007 Workshop
| Â | Dr. Stoddart | Dr. Shultz | Dr. Garcia-Martinez |
|---|---|---|---|
Characteristics of Humanized Rodent Models | Â | Â | Â |
Strain | C.B-17 scid/scid (Taconic) | NOD-SCID IL2r gamma -/- | NOD/SCID |
# mice/donor | 50–60 mice/donor | CD34+ cell isolation yields 1 × 106 cells/donor sufficient for engrafting 20- to 25 mice | 25 |
Source of human cells | Human fetal liver and thymus (20–24 g.w.) | Umbilical cord blood; mobilized hematopoeitic stem cells | Fetal liver/thymus |
Method of isolation | not applicable | Magnetic bead enrichment | Magnetic beads |
Pre-transplant treatment-mice | None | 100 cGy for newborns; 325 cGy for adults; Intravenous injection | 325 rads |
Pre-transplant treatment-cells | None | None | None |
Time frame from construction to experimental use | 18 weeks | 12 weeks | 8–12 weeks |
Location of human hematopoiesis | Thy/Liv organ | Bone marrow | Bone marrow |
Location of human Thymopoiesis | Thy/Liv organ | Mouse thymus | Human thymic tissue |
Reproducibility of engraftment (% mice engrafted) | 90–100% with >80% CD4+CD8+ | >90% of newborn and adult mice are engrafted in the bone marrow, spleen and thymus | >95% |
Identity of specific human leukocytes present | Immature and mature T cells, B cells, macrophages, plasmacytoid DCs | B cells, T cells, conventional and plasmacytoid DCs, macrophages, monocytes, RBCs, platelets | T and B cells, DCs, monocytes/macrophages, NK, NKT and Tregs |
Populated tissues | Human Thy/Liv organ | Bone marrow, thymus, spleen, lymph nodes, intestine, blood | GALT, Female and male reproductive tract, lung, bone marrow, lymph nodes, thymus, spleen, liver, peripheral blood. |
Characteristics of HIV Infection of Humanized Rodent Models | Â | Â | Â |
HIV-specific immune response | None reported | Work in progress | Yes, human IgG |
Tropism/clade of infecting HIV | X4, R5, dual/mixed; clade B | Not tested | R5 and X4 |
Target cells infected | Intrathymic progenitors (CD3-CD4+CD8-), immature and mature thymocytes, macrophages | Not tested | CD4 T cells, monocytes/macrophages, DC |
Level of plasma HIV viremia | None to highly variable | Not tested | Variable depending on stain of virus and tropism |
Duration of the infection | 5 weeks until severe depletion for X4 and dual/mixed; >6 months for R5 | Not tested | Variable depending on stain of virus and tropism |
Replication kinetics | Peaks at 3 weeks post infection (wpi) (X4 and dual/mixed), 6 wpi (R5) | Not tested | Isolate dependent |
In vivo generation of ART resistance | Not observed for NL4-3 and 3TC (no RT M184V) | Not tested | Not done |
Treatment of HIV Infection Using Humanized Rodent Models | Â | Â | Â |
ART to block transmission | Not feasible | Yes | Not tested |
Microbicide to block transmission | Not feasible | Yes | Not tested |
ART to control replication | Yes, 4 classes of licensed ARVs so far. | Yes | Not tested |
Emergence of resistance to ART | Not observed for NL4-3 and 3TC (no RT M184V) | Not done | Not tested |
Elimination of HIV reservoirs | Not performed | Not done | Not tested |
HSC gene therapy to protect progeny cells | Not performed | yes | Not tested |
CD4 T cell gene therapy to protect cells | Not performed | Not done | Not tested |
Immune-based Therapy of HIV Infection Using Humanized Rodent Models | Â | Â | Â |
Preventive HIV vaccines | Not feasible | Yes | Not tested |
Treatment HIV vaccines | Not feasible | Not done | Not tested |
Adoptive Anti-HIV Ig therapy | Feasible, but not performed | Not done | Not tested |
Adoptive Anti-HIV CTL therapy | Feasible, but not performed | Not done | Not tested |
Immunoadjuvent therapy | Not feasible | Not done | Not tested |
Investigation of HIV Pathogenesis | Â | Â | Â |
Contribution of HIV genes to pathogenesis | Nef, Env (coreceptor usage), protease | Yes | Not tested |
HIV-mediated CD4-depletion-lymphoid | Thy/Liv organ | Yes | Not tested |
HIV-mediated CD4-depletion-mucosal | Not applicable | Yes | Not tested |
Effects of co-factors on replication | Not determined | Yes | Not tested |
Effects of co-infection e.g. mTb on replication | Not determined | Yes | Not tested |
End organ dysfunction | Thy/Liv organ undergoes severe thymocyte depletion | Yes | Not tested |