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Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D-Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity.
Kronstadt, Stephanie M; Patel, Divya B; Born, Louis J; Levy, Daniel; Lerman, Max J; Mahadik, Bhushan; McLoughlin, Shannon T; Fasuyi, Arafat; Fowlkes, Lauren; Van Heyningen, Lauren Hoorens; Aranda, Amaya; Abadchi, Sanaz Nourmohammadi; Chang, Kai-Hua; Hsu, Angela Ting Wei; Bengali, Sameer; Harmon, John W; Fisher, John P; Jay, Steven M.
Affiliation
  • Kronstadt SM; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Patel DB; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Born LJ; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Levy D; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Lerman MJ; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Mahadik B; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • McLoughlin ST; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Fasuyi A; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Fowlkes L; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Van Heyningen LH; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Aranda A; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Abadchi SN; Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
  • Chang KH; Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
  • Hsu ATW; Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
  • Bengali S; Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
  • Harmon JW; Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
  • Fisher JP; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • Jay SM; Program in Molecular and Cell Biology, University of Maryland, College Park, MD, 20742, USA.
Adv Healthc Mater ; 12(20): e2300584, 2023 08.
Article in En | MEDLINE | ID: mdl-36930747
Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the 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 the effects of a 3D-printed scaffold-perfusion bioreactor system are assessed on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type widely implicated in generating EVs with therapeutic potential. The results indicate that perfusion bioreactor culture induces an ≈40-80-fold increase (depending on measurement method) in MSC EV production compared to conventional cell culture. Additionally, MSC EVs generated using the perfusion bioreactor system significantly improve 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 a major EV translational bottleneck, with the capacity for tunability for specific applications and general improvement alongside advancements in 3D-printing technologies.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Mesenchymal Stem Cells / Extracellular Vesicles Limits: Animals Language: En Journal: Adv Healthc Mater Year: 2023 Document type: Article Affiliation country: United States Country of publication: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Mesenchymal Stem Cells / Extracellular Vesicles Limits: Animals Language: En Journal: Adv Healthc Mater Year: 2023 Document type: Article Affiliation country: United States Country of publication: Germany