Scaling the manufacture of adipose tissue-derived mesenchymal stromal cells: integrated bioreactor workflows from inoculation to harvest without the need of seed train.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

BACKGROUND: The production of human mesenchymal stromal cells (hMSC) for therapeutic use requires scalable, efficient and standardized manufacturing processes that could further benefit from shortening manufacturing time, automate and simplify operations with closed systems. This study aimed to develop an industry-ready process for the expansion and integrated downstream processing of human adipose tissue-derived MSC (ASC) using xeno-free medium and microcarriers in stirred-tank bioreactors. The proposed workflow provides controlled culture conditions and is compatible with closed and large-scale cell production. METHODS: ASC were directly inoculated after thawing in stirred-tank bioreactors without the need for a seed train. Microcarrier type (Plastic vs. Synthemax II-coated) in combination with xeno-free medium and stirring profile during cell attachment (intermittent vs. continuous) were optimized in 0.2 L bioreactors and subsequently scaled-up to 2 L bioreactors using power input per volume as scale-up criteria. Focusing on further process scale-up, two strategies were evaluated: (1) bead-to-bead transfer, enabling cell migration from colonized to fresh microcarriers, and (2) enzymatic detachment followed by re-inoculation as single cells. A closed downstream process, using counterflow centrifugation was integrated as an alternative to conventional open centrifugation. RESU

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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