Search

Thierry Burnouf,1–3 Vibhuti Agrahari,4 Vivek Agrahari5 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 2International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3International PhD Program in Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Bernard J. Dunn School of Pharmacy, Shenandoah University, Winchester, VA, USA; 5CONRAD, Eastern Virginia Medical School, Arlington, VA, USACorrespondence: Vivek AgrahariCONRAD/Eastern Virginia Medical School (EVMS), 1911 North Fort Myer Drive, Suite 900, Arlington 22209, VA, USATel +1 703-276-4021Email vagrahari@conrad.org Thierry BurnoufGraduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, 250 Wu-Shin Street, Taipei 11031, TaiwanTel +886 2 2736 1661Fax +886 2 2737 4113Email thburnouf@gmail.comAbstract: The clinical development of cell therapies is revealing that extracellular vesicles (EVs) may become very instrumental as subcellular therapeutic adjuncts in human medicine. EVs are released by various types of cells, grown in culture, such as mesenchymal stromal cells, or obtained from patients or allogeneic donors. Some EV populations (especially species of exosomes and shed microvesicles) exhibit inherent roles in cell-cell communication, thanks to their ca. 30∼1000-nm nanosize and the physiological expression of cell-specific markers on their lipid bilayer membranes. Biomedical engineers are now attempting to exploit this cellular crosstalk capacity to use EVs as smart drug delivery systems that display substantial benefits in targeting, safety, and pharmacokinetics compared to synthetic nanocarriers. In parallel, the development of a set of nano-instrumentation, biochemical tools, and preclinical assays needed for optimal characterization of both naïve and drug-loaded EVs is ongoing. Although many hurdles remain, owing to the complexity of EV populations, translation of this “subcellular therapy” platform into reality is at hand and may soon change the landscape of the therapeutic arsenal in place to treat human degenerative and metabolic pathologies as well as diseases like cancer. This article provides objective opinions, balanced between unrealistic hopes of the capacity of EVs to resolve multiple clinical issues and concrete hurdles that have to be overcome to ensure that EVs are not lost in the translation phase, so that EVs can fulfill their promise by becoming a reliable therapeutic modality.Keywords: extracellular vesicle, exosome, microvesicle, drug delivery, isolation and purification, mesenchymal stromal cell, clinical translation challenge