Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D‐Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity

Autor: Stephanie M. Kronstadt, Divya B. Patel, Louis J. Born, Daniel Levy, Max J. Lerman, Bhushan Mahadik, Shannon T. McLoughlin, Arafat Fasuyi, Lauren Fowlkes, Lauren Hoorens Van Heyningen, Amaya Aranda, Sanaz Nourmohammadi Abadchi, Kai‐Hua Chang, Angela Ting Wei Hsu, Sameer Bengali, John W. Harmon, John P. Fisher, Steven M. Jay
Rok vydání: 2023
Předmět:
Zdroj: Advanced Healthcare Materials.
ISSN: 2192-2659
2192-2640
Popis: Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on development of scalable biomanufacturing approaches, especially due to the documented low levels of intrinsic EV-associated cargo that may necessitate repeated doses to achieve clinical benefit in certain applications. Thus, here we assessed effects of a 3D-printed scaffold-perfusion bioreactor system on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type heavily implicated in generating EVs with therapeutic potential. Our results indicate that perfusion bioreactor culture results in an ~40-80-fold increase, depending on measurement method, in MSC EV production compared to conventional cell culture. Additionally, we demonstrated that MSC EVs generated using the bioreactor system significantly improved wound healing in a diabetic mouse model, with increased CD31+ staining in wound bed tissue compared to animals treated with flask cell culture-generated MSC EVs. Overall, this study establishes a promising solution to major EV translational issues (i.e., scalability and low potency) with potential for adaptation to various EV-based therapeutics and capacity for improvement alongside the continuous advancements in 3D-printing technologies.
Databáze: OpenAIRE
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