Higher yield and enhanced therapeutic effects of exosomes derived from MSCs in hydrogel-assisted 3D culture system for bone regeneration

Yu, Wenting; Li, Shengnan; Guan, Xiuchen; Zhang, Ning; Xie, Xianju; Zhang, Ke; Bai, Yuxing

doi:10.1016/j.msec.2022.112646

Cited by 57 publications

(65 citation statements)

References 47 publications

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“…At present, 3D culture technology can be broadly divided into two types: material-free cultures (cell spheres formed by aggregation of cells) and material-supported cultures. Material-free 3D culture methods mainly include 3D spherical spatial boundary conditions [ 54 ], scaffold-free suspension cultures [ 55 ], systematic microcarrier screening, hydrogel-assisted 3D culture [ 56 , 57 ], and agitated culture conditions [ 58 ]. Material-supported culture methods are relatively diverse, including fibrous scaffolds [ 59 ], native extracellular matrix (ECM) bioscaffolds [ 60 ], hollow fiber bioreactors [ 61 ], quantum cell expansion systems [ 62 ], and computer-controlled bioreactors [ 63 ].…”

Section: Extracellular Environment Preconditioningmentioning

confidence: 99%

“…These approaches allow cells to establish a tight connection with the culture environment, forming a 3D structure through dynamic interactions. Owing to their suitable void structure, surface activity, mechanical strength, and biocompatibility, 3D culture systems can produce large numbers of MSCs [ 52 , 54 , 58 ] and MSC-exosomes [ 57 , 58 , 61 , 64 ] in a shorter time or within a small volume. 3D culture systems based on hollow fiber bioreactors increase the total MSC-exosome production about 19.4 times than 2D culture [ 61 ].…”

Section: Extracellular Environment Preconditioningmentioning

confidence: 99%

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Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy

Chen

Sun

Qian

et al. 2022

Stem Cells International

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Mesenchymal stem cells (MSCs) have been widely applied to regenerative medicine owing to their multiple differentiation, self-renewal, and immunomodulatory abilities. Exosomes are cell-secreted natural nanovesicles and thought to be mediators of intercellular communication and material transport. The therapeutic potential of MSCs can be largely attributed to MSC-derived exosomes (MSC-exosomes). Emerging evidence suggests that the therapeutic efficacy of MSC-exosomes is highly dependent on the status of MSCs, and optimization of the extracellular environment affects the exosomal content. Pretreatment methods including three-dimensional cultures, hypoxia, and other biochemical cues have been shown to potentially enhance the biological activity of MSC-exosomes while maintaining or enhancing their production. On the other hand, engineering means to enhance the desired function of MSC-exosomes has been rapidly gaining attention. In particular, biologically active molecule encapsulation and membrane modification can alter or enhance biological functions and targeting of MSC-exosomes. In this review, we summarize two possible strategies to improve the therapeutic activity of MSC-exosomes: preconditioning approaches and engineering exosomes. We also explore the underlying mechanisms of different strategies and discuss their advantages and limitations of the upcoming clinical applications.

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Section: Extracellular Environment Preconditioningmentioning

confidence: 99%

Section: Extracellular Environment Preconditioningmentioning

confidence: 99%

Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy

Chen

Sun

Qian

et al. 2022

Stem Cells International

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“…Fan et al encapsulated umbilical MSC-derived exosomes (UMSC-Exos) in an HA hydrogel and combined them with 3D-printed nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds [ 123 ]. Taken together, hydrogels can regulate extracellular matrix (ECM) formation, which provides a three-dimensional (3D) culture system for exosome secretion [ 89 , 124 ].…”

Section: Biomedical Exploitation Of Exosomes Delivered In Hydrogelsmentioning

confidence: 99%

Hydrogels for Exosome Delivery in Biomedical Applications

Xie

Guan

Guo

et al. 2022

Gels

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Hydrogels, which are hydrophilic polymer networks, have attracted great attention, and significant advances in their biological and biomedical applications, such as for drug delivery, tissue engineering, and models for medical studies, have been made. Due to their similarity in physiological structure, hydrogels are highly compatible with extracellular matrices and biological tissues and can be used as both carriers and matrices to encapsulate cellular secretions. As small extracellular vesicles secreted by nearly all mammalian cells to mediate cell–cell interactions, exosomes play very important roles in therapeutic approaches and disease diagnosis. To maintain their biological activity and achieve controlled release, a strategy that embeds exosomes in hydrogels as a composite system has been focused on in recent studies. Therefore, this review aims to provide a thorough overview of the use of composite hydrogels for embedding exosomes in medical applications, including the resources for making hydrogels and the properties of hydrogels, and strategies for their combination with exosomes.

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“… Cao et al (2021) found that mature dendritic cell–derived exosomes enhance osteogenic differentiation of MSCs. Moreover, some studies have focused on regulating exosomes to increase their osteogenic activity, such as aptamer-functionalized exosomes, static magnetic field–treated exosomes, exosomes endowed with plasmids, genetic engineered exosomes, hypoxic environment-treated exosomes, hydrogel-assisted 3D cultured exosomes, and exosomes with fusion peptide ( Li et al, 2022 ; Luo et al, 2019 ; Ma et al, 2022 ; Shen et al, 2022 ; Wu et al, 2021 ; Yu et al, 2022 ; Zha et al, 2021 ). In general, the treatment of exosomes increases the osteogenic ability in the bone defect microenvironment, which is beneficial for bone defect repair.…”

Section: Applications Of Bone Engineering Scaffolds With Exosomes In ...mentioning

confidence: 99%

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

Zhang

Feng

et al. 2022

Front. Bioeng. Biotechnol.

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The treatment of bone defects is still an intractable clinical problem, despite the fact that numerous treatments are currently available. In recent decades, bone engineering scaffolds have become a promising tool to fill in the defect sites and remedy the deficiencies of bone grafts. By virtue of bone formation, vascular growth, and inflammation modulation, the combination of bone engineering scaffolds with cell-based and cell-free therapy is widely used in bone defect repair. As a key element of cell-free therapy, exosomes with bioactive molecules overcome the deficiencies of cell-based therapy and promote bone tissue regeneration via the potential of osteogenesis, angiogenesis, and inflammation modulation. Hence, this review aimed at overviewing the bone defect microenvironment and healing mechanism, summarizing current advances in bone engineering scaffolds and exosomes in bone defects to probe for future applications.

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Higher yield and enhanced therapeutic effects of exosomes derived from MSCs in hydrogel-assisted 3D culture system for bone regeneration

Cited by 57 publications

References 47 publications

Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy

Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy

Hydrogels for Exosome Delivery in Biomedical Applications

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

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