期刊
STEM CELL RESEARCH & THERAPY
卷 12, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-021-02190-3
关键词
Human mesenchymal stromal cells; Extracellular vesicles; Hollow-fiber bioreactor system; Immune-profiling; Glycan; cGMP-compliant environment
资金
- Genomic Research and Development Initiative (GRDI) Phases VII
This study investigated the production of extracellular vesicles (EVs) from human bone marrow-derived mesenchymal stromal cells using a bioreactor system. The EVs showed consistency in size, concentration, immunophenotype, and glycan profile. Additionally, the EVs exhibited immuno-regulatory constituents and could be generated in large quantities over a long production period with consistent quality.
BackgroundExtracellular 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.MethodsTo 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.ResultsBioreactor-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.ConclusionsSignificantly, 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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