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Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:125-154. doi: 10.1146/annurev-pharmtox-061616-030146. Epub 2016 Oct 28.

Stem Cell Extracellular Vesicles: Extended Messages of Regeneration.

Riazifar M1,2,3,4,5,6, Pone EJ1,2,3,4,5,6, Lötvall J7,8, Zhao W1,2,3,4,5,6.

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Department of Pharmaceutical Sciences, University of California, Irvine, California 92697; email:
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California 92697.
Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, California 92868.
Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, California 92697.
Department of Biomedical Engineering, University of California, Irvine, California 92697.
Department of Biological Chemistry, University of California, Irvine, California 92697.
Krefting Research Centre, Institute of Medicine, The Sahlgrenska Academy, Göteborg University, SE-405 30 Göteborg, Sweden.
Codiak BioSciences Inc., Woburn, Massachusetts 01801.


Stem cells are critical to maintaining steady-state organ homeostasis and regenerating injured tissues. Recent intriguing reports implicate extracellular vesicles (EVs) as carriers for the distribution of morphogens and growth and differentiation factors from tissue parenchymal cells to stem cells, and conversely, stem cell-derived EVs carrying certain proteins and nucleic acids can support healing of injured tissues. We describe approaches to make use of engineered EVs as technology platforms in therapeutics and diagnostics in the context of stem cells. For some regenerative therapies, natural and engineered EVs from stem cells may be superior to single-molecule drugs, biologics, whole cells, and synthetic liposome or nanoparticle formulations because of the ease of bioengineering with multiple factors while retaining superior biocompatibility and biostability and posing fewer risks for abnormal differentiation or neoplastic transformation. Finally, we provide an overview of current challenges and future directions of EVs as potential therapeutic alternatives to cells for clinical applications.


bioengineering; drug delivery; exosomes; extracellular vesicles; microvesicles; stem cells

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