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Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
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Characterization of Human CD8(+)TCR(-) Facilitating Cells In Vitro and In Vivo in a NOD/SCID/IL2rγ(null) Mouse Model
Y Huang1, M J Elliott1, E S Yolcu1
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY.
Summary
Human facilitating cells (FCs) enhance hematopoietic stem/progenitor cell (HSPC) engraftment. Researchers identified two human FC types, CD56-negative and CD56-bright, with distinct roles in promoting HSPC homing and reconstitution without graft-versus-host disease.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- CD8(+)/TCR(-) facilitating cells (FCs) in mouse bone marrow enhance hematopoietic stem/progenitor cell (HSPC) engraftment.
- The phenotype and function of human FCs are not well-defined.
Purpose of the Study:
- To characterize the phenotype of human FCs.
- To correlate FC phenotype with their function in enhancing HSPC engraftment and preventing graft-versus-host disease (GVHD).
Main Methods:
- Phenotypic characterization of human FCs using flow cytometry.
- Assessment of FC function in promoting HSPC homing in vivo (NOD/SCID/IL2Rγnull mice).
- Evaluation of hematopoietic colony formation in vitro.
- Analysis of donor chimerism and GVHD in recipients.
Main Results:
- Human FCs comprise CD56-negative and CD56-bright subpopulations.
- CD56-negative FCs significantly promote HSPC homing and rapid reconstitution without GVHD.
- Both FC subpopulations enhance durable donor chimerism and upregulate key molecules (CXCR4, cathelicidin, β-defensin 2, Flt3 ligand) involved in HSPC homing and growth.
Conclusions:
- Human FCs directly enhance HSPC engraftment through distinct mechanisms.
- FCs represent a potential cell-based therapy for improving hematopoietic stem cell transplantation outcomes and preventing GVHD.
