title: Isolation and Characterization of Exosome from Human Embryonic Stem Cell-Derived C-Myc-Immortalized Mesenchymal Stem Cells.
abstract: Mesenchymal stem cells (MSC) are currently the cell type of choice in many cell therapy trials. The number of therapeutic applications for MSCs registered as product IND submissions with the FDA and initiation of registered clinical trials has increased substantially in recent years, in particular between 2006 and 2012. However, defined mechanisms of action underpinning the therapeutic efficacy of MSCs are lacking, but they are increasingly attributed to MSC trophic secretion rather than their differentiation potential. A promising secreted therapeutic candidate is an extracellular vesicle (EV) known as the exosome. The use of exosomes instead of cells as a therapeutic agent provides several advantages. A critical advantage is the prospect of a conventional pharmaceutical manufacturing process that is highly scalable and amenable to the stringent manufacturing process. For example, MSCs used as producers of therapeutics, and not as therapeutics per se, could be immortalized to generate infinitely expansible clonal lines to enhance the reproducible production of therapeutic exosomes. In this chapter, we will describe the immortalization of MSCs, and the production, isolation, and characterization of exosomes from immortalized MSC.
authors.affiliation: Agency for Science Technology and Research, Institute of Medical Biology, Singapore, 138648, Singapore. ruennchai.lai@imb.a-star.edu.sg.
authors.forename: Ruenn Chai
authors.initials: RC
authors.lastname: Lai
authors.affiliation: Agency for Science Technology and Research, Institute of Medical Biology, Singapore, 138648, Singapore.
authors.forename: Ronne Wee Yeh
authors.initials: RW
authors.lastname: Yeo
authors.affiliation: Agency for Science Technology and Research, Bioprocessing Technology Institute, Singapore, 138668, Singapore.
authors.forename: Jayanthi
authors.initials: J
authors.lastname: Padmanabhan
authors.affiliation: Agency for Science Technology and Research, Bioprocessing Technology Institute, Singapore, 138668, Singapore.|Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore, 117574, Singapore.
authors.forename: Andre
authors.initials: A
authors.lastname: Choo
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Health System, Singapore, 117599, Singapore.|Experimental Cardiology, University Medical Center, Utrecht, 3584CX, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Utrecht, 3511GC, The Netherlands.
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.affiliation: Agency for Science Technology and Research, Institute of Medical Biology, Singapore, 138648, Singapore.|Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim
mesh_terms: D002454:Cell Differentiation; D055354:Exosomes / Q000378:metabolism*; D057809:HEK293 Cells; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
keywords: Exosome; Immortalization; Mesenchymal stem cells