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.
Stem Cell Res Ther
; 12(1): 127, 2021 02 12.
Article
em En
| MEDLINE
| ID: mdl-33579358
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Transplante_de_medula_ossea
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Mesenquimais
/
Vesículas Extracelulares
Limite:
Humans
Idioma:
En
Revista:
Stem Cell Res Ther
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá