Influence of oxygen conditioning on the production of secretome by human mesenchymal stromal cells in stirred bioreactors
Year: 2025
Type: article
Abstract: Human Mesenchymal Stromal Cells derived from Wharton's Jelly (hWJ-MSCs) release a broad range of bioactive components, collectively known as the se-cretome. This secretome includes growth factors, cytokines, and extracellu-lar vesicles (EVs). The secretome has significant therapeutic potential such as modulating inflammation, promoting tissue repair, and inhibiting tumor proliferation. The cellular microenvironment, particularly the oxygen level, plays a critical role in influencing the quantity and quality of the secretome. In this study, we originally explored the effects of long-term oxygen condition-ing (7 days) at 2, 10, and 19% oxygen on hWJ-MSC and their secretome using stirred and controlled Ambr®250 bioreactors and Size Exclusion Chromatog-raphy (SEC). Our results demonstrate that cells cultured at 2% O 2 exhibited a significantly enhanced proliferation and a higher cell density (2.5 × 10 5 ± 4.2 × 10 4 cell/mL) compared to those at 10% O 2 (2.0 × 10 5 ± 2.6 × 10 4 cell/mL) and 19% O 2 (1.6 × 10 5 ±3.6 × 10 4 cell/mL). Furthermore, glucose uptake and lactate production were also elevated at 2% O 2 , indicating an increased metabolic activity. Surprisingly, despite a higher cell density and metabolic activity at 2% O 2 , the yield production of particles and protein per cell was reduced com-pare to the higher oxygen conditions. However, Conditioned Media (CM) and isolated EVs (EV-SEC) derived from hWJ-MSCs cultured under 2% O 2 demon-strated a superior capacity to promote osteoblast and HUVEC proliferation and migration and angiogenic potential. In conclusion, while long-term hy-poxic preconditioning (2% O 2 ) may not maximize particle and protein yields, it significantly enhances the bioactivity of the secretome in supporting cell migration, and potentially neovascularisation. These findings highlight the importance to control accurately the level of oxygen in hWJ-MSC culture to reveal an optimised regenerative potential of the secretome for therapeutic applications.
Source: Cytotherapy
Authors: Kevin Audoux, Elise Madec, Julien Branchu, Eric Olmos, Jessica Schiavi-Tritz
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
OpenAlex ID: W4417273757