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.

Autor: Gobin J; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada.; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Muradia G; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Mehic J; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Westwood C; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Couvrette L; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Stalker A; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Bigelow S; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Luebbert CC; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Bissonnette FS; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Johnston MJW; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.; Department of Chemistry, Carleton University, Ottawa, Ontario, Canada., Sauvé S; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Tam RY; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Wang L; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada., Rosu-Myles M; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada.; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada., Lavoie JR; Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada. jessie.lavoie@canada.ca.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2021 Feb 12; Vol. 12 (1), pp. 127. Date of Electronic Publication: 2021 Feb 12.
DOI: 10.1186/s13287-021-02190-3
Abstrakt: 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.
Databáze: MEDLINE
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