Autor: |
Patel DB; Fischell Dept. of Bioengineering University of Maryland College Park MD 20742., Gray KM; Fischell Dept. of Bioengineering University of Maryland College Park MD 20742., Santharam Y; Fischell Dept. of Bioengineering University of Maryland College Park MD 20742., Lamichhane TN; Fischell Dept. of Bioengineering University of Maryland College Park MD 20742., Stroka KM; Fischell Dept. of Bioengineering University of Maryland College Park MD 20742.; Greenebaum Comprehensive Cancer Center University of Maryland - Baltimore Baltimore MD 21201.; Biophysics Program University of Maryland College Park MD 20742.; Center for Stem Cell Biology and Regenerative Medicine University of Maryland - Baltimore Baltimore MD 21201., Jay SM; Fischell Dept. of Bioengineering University of Maryland College Park MD 20742.; Greenebaum Comprehensive Cancer Center University of Maryland - Baltimore Baltimore MD 21201.; Program in Molecular and Cell Biology University of Maryland College Park MD 20742. |
Jazyk: |
angličtina |
Zdroj: |
Bioengineering & translational medicine [Bioeng Transl Med] 2017 Jun 26; Vol. 2 (2), pp. 170-179. Date of Electronic Publication: 2017 Jun 26 (Print Publication: 2017). |
DOI: |
10.1002/btm2.10065 |
Abstrakt: |
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as potential therapeutic agents for numerous applications. EVs offer potential advantages over cell-based therapies with regard to safety, stability and clearance profiles, however production and potency limitations must be addressed to enable eventual translation of EV-based approaches. Thus, we sought to examine the role of specific cell culture parameters on MSC EV production and bioactivity toward informing rational design parameters for scalable EV biomanufacturing. We report significantly reduced MSC EV vascularization bioactivity, as measured by an endothelial cell gap closure assay, with increasing passage in culture by trypsinization, especially beyond passage 4. We further show that increased frequency of EV collection yielded higher numbers of EVs from the same initial number of MSCs over a 24 hr period. Finally, we demonstrate that decreased cell seeding density in culture flasks resulted in increased production of EVs per cell in MSCs and other cell types. Overall, these studies highlight the need for careful consideration of the parameters of cell passage number and cell seeding density in the production of therapeutic EVs at laboratory scale and for rational design of large-scale EV biomanufacturing schemes. |
Databáze: |
MEDLINE |
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