a new mesenchymal stem cell (msc) paradigm polarization into a pro-inflammatory msc1 or an immunosuppressive msc2 phenotype间充质干细胞(msc)的新范式极化炎性msc1或免疫抑制msc2表型.pdfVIP

A New Mesenchymal Stem Cell (MSC) Paradigm: Polarization into a Pro-Inflammatory MSC1 or an Immunosuppressive MSC2 Phenotype 1 2 2 2 Ruth S. Waterman , Suzanne L. Tomchuck , Sarah L. Henkle , Aline M. Betancourt * 1 Department of Anesthesiology, Tulane University, New Orleans, Louisiana, United States of America, 2 Department of Microbiology and Immunology, Tulane Cancer Center, Tulane Center for Gene Therapy, Tulane University, New Orleans, Louisiana, United States of America Abstract Background: Our laboratory and others reported that the stimulation of specific Toll-like receptors (TLRs) affects the immune modulating responses of human multipotent mesenchymal stromal cells (hMSCs). Toll-like receptors recognize ‘‘danger’’ signals, and their activation leads to profound cellular and systemic responses that mobilize innate and adaptive host immune cells. The danger signals that trigger TLRs are released following most tissue pathologies. Since danger signals recruit immune cells to sites of injury, we reasoned that hMSCs might be recruited in a similar way. Indeed, we found that hMSCs express several TLRs (e.g., TLR3 and TLR4), and that their migration, invasion, and secretion of immune modulating factors is drastically affected by specific TLR-agonist engagement. In particular, we noted diverse consequences on the hMSCs following stimulation of TLR3 when compared to TLR4 by our low-level, short-term TLR-priming protocol. Principal Findings: Here we extend our studies on the effect on immune modulation by specific TLR-priming of hMSCs, and based on our findings, propose a new paradigm for hMSCs that takes its cue from the monocyte literature. Specifically, that hMSCs can be polarized by downstream TLR signaling into two homo