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Mesenchymal Stem Cells: Diseases and Cure
Author(s) -
Shi Songtao
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.359.2
Subject(s) - mesenchymal stem cell , immunology , cancer research , fas ligand , immune system , medicine , stem cell , apoptosis , biology , microbiology and biotechnology , pathology , programmed cell death , biochemistry
Mesenchymal stem cells (MSCs) are a population of hierarchical postnatal stem cells with the potential to multiple differentiations and thus serve as a promising cell source for regenerative medicine in terms of forming mineralized tissues to replace damaged and diseased tissues. MSCs have been successfully used for mineralized and soft tissue regeneration in animal models and clinics. MSCs display profound immunomodulatory properties by inhibiting proliferation and function of several major immune cells, such as dendritic cells, T and B lymphocytes, and natural killer (NK) cells In fact, MSC‐based therapy has been successfully applied in various human diseases, including graft versus host disease (GvHD), systemic lupus erythematosus (SLE), rheumatoid arthritis, autoimmune encephalomyelitis, inflammatory bowel disease, and multiple sclerosis. We found that systemic infusion of MSCs induced transient T‐cell apoptosis via the Fas ligand (FasL)‐dependent Fas pathway and could ameliorate disease phenotypes in fibrillin‐1 mutated systemic sclerosis (SS) and dextran sulfate sodium‐induced experimental colitis. Mechanistic analysis revealed that Fas‐regulated monocyte chemotactic protein 1 (MCP‐1) secretion by MSCs recruited T‐cells for FasL‐mediated apoptosis. The apoptotic T‐cells subsequently triggered macrophages to produce high levels of TGFb which in turn led to the upregulation of Tregs and, ultimately, to immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying MSC‐based immunotherapy involving coupling via Fas/FasL to induce T‐cell apoptosis. Recent studies show that MSC deficiency contributes to a variety of diseases, such as osteoporosis, SLE, SS, and benign tumors. Cell and drug therapies can rescue these MSC‐related diseases.