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Updated: May 3, 2026
Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
Mouse Flk-1+Sca-1- mesenchymal stem cells: functional plasticity in vitro and immunoregulation in vivo
Zhu Xishan1, Yu Haojun, He Baoxin
11 Institute of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. 2 Institute of Basic medicine, Peking Union Medical College, Department of Cell Biology, Beijing 100005, China. 3 Address correspondence to: Ren Jun, Ph.D., M.D., Institute of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Objectives:
Mesenchymal stem cells (MSCs) represent a powerful tool in regenerative medicine because of their differentiation and migration capacities. Moreover, the immunomodulatory ability of MSCs may be used to develop therapies for the treatment of autoimmune diseases.
Methods:
In this study, we isolated Flk-1Sca-1 MSCs from bone marrow (bMSCs). Next, we studied their biological characteristics and immunologic functions. We also investigated their effects on graft-versus-host disease (GVHD) associated with allogeneic bone marrow transplantation in mice.
Results:
Flk-1Sca-1 bMSCs were able to differentiate into fat and cartilage cells, indicating that the isolated cells had stem cell properties. They could also suppress alloantigen-induced T cell proliferation in vitro in a dose-dependent manner. Infusion of bMSCs into allogeneic bone marrow-transplanted mice alleviated the lethal GVHD that occurred in control recipient mice. There was significantly lower mortality among the recipients of the Flk-1Sca-1 bMSCs that also ameliorated the clinical symptoms and GVHD histopathology. Beneficial effects on GVHD by Flk-1Sca-1 bMSCs were also observed when MSCs were engineered to express anti-inflammatory cytokines IL-4 and IL-10 and decrease expression of proinflammatory cytokines IFN-γ, TNF-α, and IL-2.
Conclusion:
Flk-1Sca-1 bMSCs have stem cell properties and can efficiently ameliorate the GVHD associated with allogeneic bone marrow transplantation in mice.
