Cellular Phenotype and Extracellular Vesicles

Early work on platelet and erythrocyte vesicles interpreted the phenomena as a discard of material from cells. Subsequently vesicles were studied as possible vaccines and most recently there has been a focus on the effects of vesicles on cell fate. Recent studies have indicated that extracellular vesicles, previously referred to as microvesicles or exosomes, have the capacity to change the phenotype of neighboring cells. Extensive work has shown that vesicles derived from either lung or liver can enter bone marrow cells, (this is a prerequisite) and alter their fate towards that of the originating liver and lung tissue. Lung vesicles interacted with bone marrow cells result in the bone marrow cells expressing surfactants A B C D, Clara cell protein and aquaporin 5 mRNA. In a similar vein, liver derived vesicles induce albumin mRNA in target marrow cells. The vesicles contain protein, mRNA, microRNA, and non-coding RNA and variably some DNA. This genetic package is delivered to cells and alters phenotype. Further studies have shown that initially the altered phenotype is due to transfer of mRNA and a transcriptional modulator, but the long term epigenetic changes are induced via transfer of a transcriptional factor, the mRNA is rapidly degraded in the cell. Studies on the capacity of vesicles to restore injured tissue have been quite informative. Mesenchymal stem cell derived vesicles are able to reverse the injury to damaged liver and kidney. Other studies have shown that mesenchymal stem cell derived vesicles can reverse radiation toxicity of bone marrow stem cells. Extracellular vesicles offer an intriguing strategy for treating a number of diseases characterized by tissue injury.

Quesenberry PJ1, Goldberg L, Aliotta JM, Pereira M, Wen S, Camussi G, Dooner MS. (2014) Cellular Phenotype and Extracellular Vesicles: Basic and Clinical Considerations. Stem Cells Dev [Epub ahead of print]. [abstract]

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