Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment |
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Authors: | Divya B Patel Marco Santoro Louis J Born John P Fisher Steven M Jay |
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Institution: | 1. Fischell Department of Bioengineering, University of Maryland, 3102 A. James Clark Hall, College Park, MD 20742, United States;2. Center for Engineering Complex Tissues, University of Maryland, 3238 Jeong H. Kim Engineering Building, College Park, MD 20742, United States;3. Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Baltimore, MD 21201, United States;4. Program in Molecular and Cell Biology, University of Maryland, College Park, MD 20742, United States |
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Abstract: | Extracellular vesicles (EVs), including exosomes, microvesicles, and others, have emerged as potential therapeutics for a variety of applications. Pre-clinical reports of EV efficacy in treatment of non-healing wounds, myocardial infarction, osteoarthritis, traumatic brain injury, spinal cord injury, and many other injuries and diseases demonstrate the versatility of this nascent therapeutic modality. EVs have also been demonstrated to be effective in humans, and clinical trials are underway to further explore their potential. However, for EVs to become a new class of clinical therapeutics, issues related to translation must be addressed. For example, approaches originally developed for cell biomanufacturing, such as hollow fiber bioreactor culture, have been adapted for EV production, but limited knowledge of how the cell culture microenvironment specifically impacts EVs restricts the possibility for rational design and optimization of EV production and potency. In this review, we discuss current knowledge of this issue and delineate potential focus areas for future research towards enabling translation and widespread application of EV-based therapeutics. |
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Keywords: | EV extracellular vesicle miRNA microRNA 2D two-dimensional 3D three-dimensional ECM extracellular matrix KEC kidney epithelial cell CEC corneal epithelial cell RC recombinant collagen MSC mesenchymal stem cells ESC embryonic stem cell E1MYC16 3 MYC-immortalized ESC-derived MSC line CMSC3A1 MYC-immortalized umbilical cord-derived MSC line PC12 neuronal progenitor cells MAPK p38 mitogen activated protein kinase SMC smooth muscle cells HUVEC human umbilical vein endothelial cells SMA smooth muscle actin EC endothelial cell VE-cad vascular endothelial cadherin vWF von-Willebrand factor FDA US Food and Drug Administration Extracellular vesicle Exosome Mesenchymal stem cell Biomanufacturing Microenvironment |
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