Development and function of myeloid-derived suppressor cells generated from mouse embryonic and hematopoietic stem
Zuping Zhou1, Deborah L French, Ge Ma
1Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Stem Cells (Dayton, Ohio)
|January 15, 2010
Summary
Functional myeloid-derived suppressor cells (MDSCs) can be generated from stem cells. These in vitro-derived MDSCs show potent immune suppression and prevent graft-versus-host disease in mice.
Area of Science:
- Immunology
- Stem Cell Biology
- Transplantation Science
Background:
- Myeloid-derived suppressor cells (MDSCs) show promise for treating transplantation and autoimmune diseases.
- A major hurdle in developing MDSC-based therapies is the lack of a reliable MDSC source.
Purpose of the Study:
- To investigate the efficient generation of functional MDSCs from mouse embryonic stem (ES) cells and bone marrow hematopoietic stem (HS) cells.
- To characterize the subpopulations and suppressive functions of in vitro-derived MDSCs.
Main Methods:
- Generation of MDSCs from mouse ES and HS cells in vitro.
- Characterization of MDSC subpopulations using flow cytometry (CD115, Ly-6C, Gr-1, F4/80).
- Assessment of MDSC suppressive activity against T-cell proliferation and induction of regulatory T cells (Tregs).
- Evaluation of in vivo efficacy using a mouse model of graft-versus-host disease (GVHD).
Main Results:
- Efficient generation of two homogenous MDSC subpopulations (CD115(+)Ly-6C(+) and CD115(+)Ly-6C(-)) from ES and HS cells.
- In vitro-derived MDSCs exhibit robust T-cell suppression via nitric oxide (NO) and interleukin-10 (IL-10).
- ES- and HS-MDSCs demonstrate superior suppressive activity and Treg induction compared to tumor-derived MDSCs.
- Adoptive transfer of ES-MDSCs significantly prevented lethal graft-versus-host disease, achieving 82% long-term survival.
Conclusions:
- Functional MDSCs can be efficiently generated in vitro from ES and HS cells.
- These in vitro-derived MDSCs possess potent immunosuppressive properties and therapeutic potential.
- Successful generation of MDSCs in vitro is a critical advancement for potential clinical applications in transplantation and autoimmune diseases.
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