Treatment with Mesenchymal Stem Cells Effective in Animal Autoimmune Disease Models

A paper demonstrated how autoimmune disorders could be controlled by infusions of mesenchymal stem cells.

Mesenchymal stem cells (MSC) are adult stem cells traditionally found in the bone marrow. However, mesenchymal stem cells can also be isolated from other tissues including cord blood, peripheral blood, fallopian tube, and fetal liver and lung. MSCs are multipotent stem cells, which differentiate to form adipocytes, cartilage, bone, tendons, muscle, and skin.

Investigators at the University of Southern California (Los Angeles, USA) worked with animal models of various autoimmune disorders. In the current study they showed that in mice systemic infusion of bone marrow MSCs induced transient T-cell apoptosis via the FAS ligand (FASL)-dependent FAS pathway and could ameliorate autoimmune disease symptoms in fibrillin-1 mutated systemic sclerosis (SS) and dextran-sulfate-sodium-induced experimental colitis.

Fas ligand (FasL or CD95L) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Binding for FASL to the FAS receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer. Bone marrow MSCs that lacked the gene for production of FASL did not induce T cell apoptosis in recipients, and could not ameliorate SS and colitis.

Mechanistic analysis that was published in the April 26, 2012, online edition of the journal Cell Stem Cell revealed that FAS-regulated monocyte chemotactic protein 1 (MCP-1) secretion by bone marrow MSCs recruited T-cells for FASL-mediated apoptosis. The apoptotic T cells subsequently triggered macrophages to produce high levels of transforming growth factor beta (TGF-beta), which in turn led to the upregulation of CD4+CD25+Foxp3+ regulatory T-cells and, ultimately, immune tolerance.

“The identification of the cellular workings responsible for the stem cell treatments' success may eventually help doctors find optimal cell-based treatment for some immune diseases,” said senior author Dr. Songtao Shi, professor of molecular biology at the University of Southern California.

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