Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment

Cha, Kyung-Yup; Cho, Woongjin; Park, Sunghyun; Ahn, Jinsung; Park, Hyoeun; Baek, Inho; Lee, Minju; Lee, Sunjun; Arai, Yoshie; Lee, Soo−Hong

doi:10.1016/j.jconrel.2022.12.053

Cited by 12 publications

(15 citation statements)

References 58 publications

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“…Moreover, studies have identified the involvement of macrophages and other immune cells in the progression of articular cartilage [ 52 – 54 ]. ETS/CS has been found to significantly inhibit the release of VEC-related chemokines, which is beneficial for alleviating the chemotaxis of local immune cells like macrophages.…”

Section: Discussionmentioning

confidence: 99%

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

Tu,

Pan,

Wang

et al. 2024

Biomater Res

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Background: In the environment of cartilage injury, the activation of vascular endothelial cell (VEC), marked with excessive CD62E and reactive oxygen species (ROS), can affect the formation of hyaluronic cartilage. Therefore, we developed a CD62E- and ROS-responsive drug delivery system using E-selectin binding peptide, Thioketal, and silk fibroin (ETS) to achieve targeted delivery and controlled release of Clematis triterpenoid saponins (CS) against activated VEC, and thus promote cartilage regeneration. Methods: We prepared and characterized ETS/CS and verified their CD62E- and ROS-responsive properties in vitro. We investigated the effect and underlying mechanism of ETS/CS on inhibiting VEC activation and promoting chondrogenic differentiation of bone marrow stromal cells (BMSCs). We also analyzed the effect of ETS/CS on suppressing the activated VEC-macrophage inflammatory cascade in vitro. Additionally, we constructed a rat knee cartilage defect model and administered ETS/CS combined with BMSC-containing hydrogels. We detected the cartilage differentiation, the level of VEC activation and macrophage in the new tissue, and synovial tissue. Results: ETS/CS was able to interact with VEC and inhibit VEC activation through the carried CS. Coculture experiments verified ETS/CS promoted chondrogenic differentiation of BMSCs by inhibiting the activated VEC-induced inflammatory cascade of macrophages via OPA1-mediated mitochondrial homeostasis. In the rat knee cartilage defect model, ETS/CS reduced VEC activation, migration, angiogenesis in new tissues, inhibited macrophage infiltration and inflammation, promoted chondrogenic differentiation of BMSCs in the defective areas. Conclusions: CD62E- and ROS-responsive ETS/CS promoted cartilage repair by inhibiting VEC activation and macrophage inflammation and promoting BMSC chondrogenesis. Therefore, it is a promising therapeutic strategy to promote articular cartilage repair.

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Section: Discussionmentioning

confidence: 99%

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

Tu,

Pan,

Wang

et al. 2024

Biomater Res

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“…One widely used strategy for loading the desired proteins of interest into EVs is genetic engineering of the host cells by transfecting the cells with the gene of interest (Cha et al., 2023, Cui et al., 2023, Herrmann et al., 2021). The endogenous loading method is less complex if the parent cell directly secretes EVs encapsulating the desired molecule (Kawata et al., 2021).…”

Section: Ev‐engineering and Drug‐loading Strategies For Ev‐mediated D...mentioning

confidence: 99%

“…The first‐ever siRNA interference‐based therapy approved by the FDA for hereditary transthyretin amyloidosis was encapsulated in such membrane vesicles (Food, 2018). In this context, there is compelling evidence that these membrane‐based nanoparticles, more importantly, mesenchymal stem cell‐derived EVs (MSC‐EVs), have undergone tremendous advancements in their utility as biomarkers and therapeutics of various organ conditions such as lung injury/disease (Sharma et al., 2022, Zhao et al., 2022), liver regeneration/injury (Lu et al., 2022, Zhang et al., 2023), bone repair/bone tissue regeneration (Cha et al., 2023, Huang et al., 2023, Warmink et al., 2023), graft‐versus‐host disease (Madel et al., 2023), wound healing (Kim et al., 2023, Las Heras et al., 2022), COVID‐19 induced infection (Chutipongtanate et al., 2022), blood‐brain‐barrier disruption (BBB) (Qiu et al., 2022), and various neurodegenerative disorders (Xu et al., 2022). Studies indicate that these EVs are the primary and fundamental paracrine effectors of MSCs and can effectively replicate the therapeutic properties of MSCs (Kou et al., 2022, Tsiapalis et al., 2023).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐derived extracellular vesicles: Recent therapeutics and targeted drug delivery advances

Bhat,

Malik,

Yadav

et al. 2024

J of Extracellular Bio

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The targeted drug delivery field is rapidly advancing, focusing on developing biocompatible nanoparticles that meet rigorous criteria of non‐toxicity, biocompatibility, and efficient release of encapsulated molecules. Conventional synthetic nanoparticles (SNPs) face complications such as elevated immune responses, complex synthesis methods, and toxicity, which restrict their utility in therapeutics and drug delivery. Extracellular vesicles (EVs) have emerged as promising substitutes for SNPs, leveraging their ability to cross biological barriers, biocompatibility, reduced toxicity, and natural origin. Notably, mesenchymal stem cell‐derived EVs (MSC‐EVs) have garnered much curiosity due to their potential in therapeutics and drug delivery. Studies suggest that MSC‐EVs, the central paracrine contributors of MSCs, replicate the therapeutic effects of MSCs. This review explores the characteristics of MSC‐EVs, emphasizing their potential in therapeutics and drug delivery for various diseases, including CRISPR/Cas9 delivery for gene editing. It also delves into the obstacles and challenges of MSC‐EVs in clinical applications and provides insights into strategies to overcome the limitations of biodistribution and target delivery.

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“…Despite significant advancements in bone regenerative medicine over the years, engineering bone tissue requires the generation of a highly organized vasculature. To achieve this, research has started moving toward coculture systems for generating bone tissues. , …”

Section: Overview Of Different Techniques For Coculturing Cellsmentioning

confidence: 99%

“…To achieve this, research has started moving toward coculture systems for generating bone tissues. 74,75 In a study by Narbat et al, photolithography was utilized to engineer a 3D construct with tunable angiogenic and osteogenic niches and to study its potential for the formation of vascularized bone tissue. 76 Using a two-step photolithography technique, the stiffness of the hydrogel and the distribution of cells within the patterned hydrogel were regulated (Figure 6a).…”

Section: Application Of Coculturing In Bone Tissuementioning

confidence: 99%

Generation of Patterned Cocultures in 2D and 3D: State of the Art

Joshi,

Singh

2023

ACS Omega

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Cells inside the body are embedded into a highly structured microenvironment that consists of cells that lie in direct or close contact with other cell types that regulate the overall tissue function. Therefore, coculture models are versatile tools that can generate tissue engineering constructs with improved mimicking of in vivo conditions. While there are many reviews that have focused on pattering a single cell type, very few reviews have been focused on techniques for coculturing multiple cell types on a single substrate with precise control. In this regard, this Review covers various technologies that have been utilized for the development of these patterned coculture models while mentioning the limitations associated with each of them. Further, the application of these models to various tissue engineering applications has been discussed.

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Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment

Cited by 12 publications

References 58 publications

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

Mesenchymal stem cell‐derived extracellular vesicles: Recent therapeutics and targeted drug delivery advances

Generation of Patterned Cocultures in 2D and 3D: State of the Art

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