Extracellular vesicles (EVs) are active vesicles secreted by most cells, and they mediate various physiological and pathological functions, such as cell homeostasis, infection transmission, tumor development, etc., by participating in intercellular material transfer. Thus, the discovery of EVs as mediators of intercellular communication has fueled the exploration of their therapeutic potential. A large number of studies suggest that the drug delivery and therapeutic capabilities of EV can be extended to the treatment of various diseases. Although natural EV or engineered EV are considered to be effective therapeutic drugs, their clinical application remains a challenge. Large-scale and efficient production of EVs with minimal batch-to-batch variability and efficacy variability following compliance with international biologics norms is necessary to enhance the therapeutic potential of EV. Creative Biolabs has established a large-scale mass-production EV platform and continuously optimizes the culture cell process and EV production process, which can provide the most efficient large-scale EV extraction service for global customers.

Large-Scale Cell Culture Service

The contents of EV are diverse, depending on their function and the type of donor cell. In addition, the production efficiency and stability of EV are affected by factors such as the microenvironment and culture conditions of the donor cells. Creative Biolabs can provide EV endogenous loading service, endogenous targeting service, and endogenous labeling service by transforming donor cells, strictly control the cell culture conditions, and cultivate the cells specified by customers in high density and on a large scale.

Large-scale Extracellular Vesicle Isolation and Purification Service

In previous studies, the most commonly used methods for extracting EV include ultracentrifugation, precipitation, size exclusion chromatography, affinity capture, etc. However, these methods have low yield and high cost, and it is difficult to realize industrialization and clinical application for a large amount of cell supernatant. Therefore, Creative Biolabs has established a large-scale mass-producing EV platform with tangential flow ultrafiltration (TFF) concentration pretreatment combined with classical EV separation methods by introducing advanced technologies and further improving and enhancing them. This method has the advantages of simple operation, controllable parameters, and short time consumption, and can process large volumes of feed liquid, thereby obtaining a large number of high-purity EVs for subsequent use.

Fig.1 Schematic workflow for serum-free large-scale EV production from AML cell lines. (Kim, 2021)

Extracellular Vesicle Product Testing and Packaging Service

EV products obtained from different batches before and after freeze-thawing need to be tested for mycoplasma, endotoxin, particle size, markers, morphology, drug loading rate, etc., to control the variance of EV products between batches. Then, EV products that meet the standards are freeze-dried into a powder state for long-distance transportation and long-distance storage. Creative Biolabs can provide the most rigorous EV identification service to help customers control batch-to-batch differences and high-quality large-scale freeze-drying technical services to ensure the biological activity of EV.

Fig.2 Schematic diagram of freeze drying. (Bahr, 2020)

Creative Biolabs has been continuously innovating EV manufacturing technology to help customers achieve large-scale EV production from research and development to clinical practice. If you need large-scale EVs, please contact us without hesitation to propose your target donor cells and loaded drugs. Our professional team will formulate the most suitable large-scale separation and purification scheme according to the research needs of customers to prepare high-quality EV products of different specifications.

References

1. Binder, HM.; Maeding, N.; et al. Scalable enrichment of immunomodulatory human acute myeloid leukemia cell line-derived extracellular vesicles. Cells. 2021. 10(12).
2. Bahr, MM.; Amer, MS.; et al. Preservation techniques of stem cells extracellular vesicles: a gate for manufacturing of clinical grade therapeutic extracellular vesicles and long-term clinical trials. International Journal of Veterinary Science and Medicine. 2020. 8(1):1-8.

• Isolation and Purification Services
• Characterization and Quantification Services
• Extracellular Vesicle Profiling Services
• Modification Services of Extracellular Vesicle
• Functional Research and Verification Services of Extracellular Vesicle