Large-Scale Preparation of Synovial Fluid Mesenchymal Stem Cell-Derived Exosomes by 3D Bioreactor Culture

Duan, Li; Li, Xingfu; Xu, Xiao Gang; Xu, Limei; Wang, Daping; Ouyang, Kan; Liang, Yujie

doi:10.3791/62221-v

Cited by 6 publications

(7 citation statements)

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“…They cultured mesenchymal stem cells (MSCs) in a dynamic three-dimensional (3D) culture system after by attaching them to microcarrier beads. Application of this method has generated large amounts of exosomes with good manufacturing practice (GMP) grade for clinical osteoarthritis treatment [ 53 ]. Patel et al also used a 3D printed biomaterial scaffold-perfusion bioreactor system to assess the dynamic culture response to extracellular vesicle production by endothelial cells (ECs) and found that this system can increase exosome production by more than 100-fold [ 54 ], while for other cells the yield may not be so high.…”

Section: Improvements In Biomimetic Exosomesmentioning

confidence: 99%

“…Patel et al also used a 3D printed biomaterial scaffold-perfusion bioreactor system to assess the dynamic culture response to extracellular vesicle production by endothelial cells (ECs) and found that this system can increase exosome production by more than 100-fold [ 54 ], while for other cells the yield may not be so high. For example, when mesenchymal stem cells (MSCs) cultured in 3D bioreactor, the production of exosomes in the supernatant was 2 times higher than in 2D culture [ 53 ]. And although 3D culture can significantly increase exosome production, it has also been found that the morphology and composition of exosomes can also be significantly altered.…”

Section: Improvements In Biomimetic Exosomesmentioning

confidence: 99%

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Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform

Xu,

Wen

et al. 2023

Materials Today Bio

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Section: Improvements In Biomimetic Exosomesmentioning

confidence: 99%

Section: Improvements In Biomimetic Exosomesmentioning

confidence: 99%

Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform

Xu,

Wen

et al. 2023

Materials Today Bio

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“…Cell culture is currently one of the main sources of exosomes, while its production and scale are still challenging. In terms of scale‐up production, several strategies have been developed, including the use of bioreactors, 233 while the cost/yield is still economically unsuitable for clinical application. Alternative sources, including blood, milk, and plant, to obtain exosomes or exosome‐like vesicles may allow for lower production costs and shorter production times 234,235 .…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Nanomaterials for mRNA‐based therapeutics: Challenges and opportunities

Liu

Yang

et al. 2023

Bioengineering & Transla Med

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Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into the host genome and does not need to enter the nucleus for transfection, and it can be expressed even in nondividing cells. Therefore, mRNA‐based therapeutics provide a promising strategy for clinical treatment. However, the efficient and safe delivery of mRNA remains a crucial constraint for the clinical application of mRNA therapeutics. Although the stability and tolerability of mRNA can be enhanced by directly retouching the mRNA structure, there is still an urgent need to improve the delivery of mRNA. Recently, significant progress has been made in nanobiotechnology, providing tools for developing mRNA nanocarriers. Nano‐drug delivery system is directly used for loading, protecting, and releasing mRNA in the biological microenvironment and can be used to stimulate the translation of mRNA to develop effective intervention strategies. In the present review, we summarized the concept of emerging nanomaterials for mRNA delivery and the latest progress in enhancing the function of mRNA, primarily focusing on the role of exosomes in mRNA delivery. Moreover, we outlined its clinical applications so far. Finally, the key obstacles of mRNA nanocarriers are emphasized, and promising strategies to overcome these obstacles are proposed. Collectively, nano‐design materials exert functions for specific mRNA applications, provide new perception for next‐generation nanomaterials, and thus revolution of mRNA technology.

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“…Some progress has been made in improving the yield of exosomes including generation of immortalized MSC lines for exosome production, [ 19,20 ] pretreatment of MSCs, [ 21,22 ] and development of bioreactors. [ 23 ] While these strategies have shown promise in production rate and potency of exosomes, yet studies reporting the rational design approaches for biomanufacturing of exosomes are limited. Highlighting that, even though, it is expected that the cell culture conditions that impact the parental cell identity will influence exosome production, the relationships between these parameters and exosome yield and function are not well known.…”

Section: Introductionmentioning

confidence: 99%

Effect of extracellular matrices on production and potency of mesenchymal stem cell‐derived exosomes

Somadder,

Faraj,

Datta

et al. 2024

Biotechnology Journal

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Mesenchymal stem cell (MSC) derived exosomes have emerged as potential acellular therapeutics for various tissue regenerative applications. However, successful clinical translation of exosome‐based therapy is limited by lack of a structured production platform. Thus, in this study, the effect of decellularized extracellular matrix (dECM) was assessed on the production and potency of exosomes secreted by bone marrow‐derived human MSCs. The results indicate that there was a ∼2‐fold increase in MSC‐exosome production when MSCs were cultured on dECM compared to TCP. Further, our study revealed that dECM generation induced by ascorbic acid (AA) up to 100 µg mL−1 highly increased exosome yield thereby indicating a potential scale up method for MSC exosome production. The bioactivity of exosomes was investigated by their ability to improve the healing of wounded human skin explants. Wound closure was enhanced in the presence of exosomes isolated from MSCs cultured on ascorbic acid‐induced dECM compared to TCP generated MSC‐exosomes. In summary, this study suggests a promising solution to a major bottleneck in large‐scale production of MSC exosomes for cell‐free therapy.

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Large-Scale Preparation of Synovial Fluid Mesenchymal Stem Cell-Derived Exosomes by 3D Bioreactor Culture

Cited by 6 publications

References 0 publications

Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform

Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform

Nanomaterials for mRNA‐based therapeutics: Challenges and opportunities

Effect of extracellular matrices on production and potency of mesenchymal stem cell‐derived exosomes

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