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Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell. | LitMetric

AI Article Synopsis

  • Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) produce extracellular vesicles (EVs) that show promise for treating immune-mediated diseases, and using bioreactor systems could provide a better way to produce these EVs for clinical use.
  • In a study, EVs were successfully harvested from hBM-MSCs grown in a hollow-fiber bioreactor, with consistent size, concentration, and immunogenicity across four different donors, indicating reliable production.
  • The findings suggest that EVs from hBM-MSCs contain beneficial immuno-regulatory factors and can be produced on a large scale, making them a strong candidate for further clinical applications in treating immune-related conditions.

Article Abstract

Background: Extracellular vesicles (EVs) produced by human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are currently investigated for their clinical effectiveness towards immune-mediated diseases. The large amounts of stem cell-derived EVs required for clinical testing suggest that bioreactor production systems may be a more amenable alternative than conventional EV production methods for manufacturing products for therapeutic use in humans.

Methods: To characterize the potential utility of these systems, EVs from four hBM-MSC donors were produced independently using a hollow-fiber bioreactor system under a cGMP-compliant procedure. EVs were harvested and characterized for size, concentration, immunophenotype, and glycan profile at three separate intervals throughout a 25-day period.

Results: Bioreactor-inoculated hBM-MSCs maintained high viability and retained their trilineage mesoderm differentiation capability while still expressing MSC-associated markers upon retrieval. EVs collected from the four hBM-MSC donors showed consistency in size and concentration in addition to presenting a consistent surface glycan profile. EV surface immunophenotypic analyses revealed a consistent low immunogenicity profile in addition to the presence of immuno-regulatory CD40 antigen. EV cargo analysis for biomarkers of immune regulation showed a high abundance of immuno-regulatory and angiogenic factors VEGF-A and IL-8.

Conclusions: Significantly, EVs from hBM-MSCs with immuno-regulatory constituents were generated in a large-scale system over a long production period and could be frequently harvested with the same quality and quantity, which will circumvent the challenge for clinical application.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880218PMC
http://dx.doi.org/10.1186/s13287-021-02190-3DOI Listing

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