Mesenchymal Stem Cells Use Extracellular Vesicles (Microvesicles & Exosomes) to Transfer Depolarized Mitochondria & Shuttle TLR-Signaling Repressive miRNAs to Macrophages in Response to Oxidative Stress

A team led by scientists from the Florida campus of The Scripps Research Institute (TSRI) and the University of Pittsburgh has shown, for the first time, how one set of specialized cells survives under stress by manipulating the behavior of key immune system cells. The new study, published online on October 7, 2015 in an open-access article in Nature Communications, involved mesenchymal stem cells (which live in bone marrow and can differentiate into several different cell types used in bone and connective tissue) and macrophages (immune cells that usually respond to infectious agents or damaged cells by engulfing and consuming them). “This is the first time anyone has shown how mesenchymal stem cells provide for their own survival by recruiting and then suppressing normal macrophage activity,” said TSRI Professor Donald G. Phinney, who led the study, together with University of Pittsburgh Associate Professor Luis A. Ortiz, Ph.D. “This finally puts the crosstalk between these cells into the context of cell survival.” The team’s experiments showed that, like all other cells, mesenchymal stem cells (MSCs) experience stress due to tissue injury and inflammation. When this stress results in damage to the mitochondria (the power houses of the cell), the MSCs recruit the immune system’s macrophages—but in an unusual way. By re-engineering macrophage action with secreted microRNA (in MSC-derived exosomes), the stem cells protect themselves from being targeted and, instead, package their damaged mitochondria into microvesicles (MVs) and send them out to be engulfed by the macrophage. Once macrophages subsume the damaged mitochondria, the macrophages are able to re-purpose the mitochondria for their own use, replenishing their own energy supplies. Blocking the exchange of damaged mitochondrial to macrophages causes death of the MSCs.
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