&lt;p&gt;Bone-Targeted Extracellular Vesicles from Mesenchymal Stem Cells for Osteoporosis Therapy&lt;/p&gt;

Wang, Yayu; Yao, Jie; Cai, Lizhao; Liu, Tong; Wang, Xiaogang; Zhang, Ye; Zhou, Zhen; Li, Tingwei; Liu, Minyi; Lai, Renfa; Liu, Xiangning

doi:10.2147/ijn.s263756

Cited by 54 publications

(35 citation statements)

References 56 publications

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“… 51 In a previous study, the researchers observed that unless combined with alendronate, the mouse MSC-EVs did not target bone tissues. 52 This result was in line with that observed in this study, which showed that the exogenous WJ-MSC-EVs after systemic injection failed to target the femurs or other bond regions in OVX mice or the healthy mice group. This result was performed by IVIS fluorescent imaging after mice were systemically injected with DIR-labeled MSC-EVs.…”

Section: Discussionsupporting

confidence: 92%

Multiplexed Molecular Imaging Strategy Integrated with RNA Sequencing in the Assessment of the Therapeutic Effect of Wharton’s Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles for Osteoporosis

Lu¹,

Chen²,

Ke³

et al. 2021

IJN

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Introduction:Osteoporosis is a result of an imbalance in bone remodeling. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been considered as a potentially promising treatment for osteoporosis. However, the therapeutic effect, genetic alterations, and in vivo behavior of exogenous EVs for osteoporosis in mice models remain poorly understood. Methods: A multiplexed molecular imaging strategy was constructed by micro-positron emission tomography (µPET)/computed tomography (CT), µCT, and optical imaging modality which reflected the osteoblastic activity, microstructure, and in vivo behavior of EVs, respectively. RNA sequencing was used to analyze the cargo of EVs, and the bone tissues of ovariectomized (OVX) mice post EV treatment. Results: The result of [ 18 F]NaF µPET showed an increase in osteoblastic activity in the distal femur of EV-treated mice, and the bone structural parameters derived from µCT were also improved. In terms of in vivo behavior of exogenous EVs, fluorescent dye-labeled EVs could target the distal femur of mice, whereas the uptakes of bone tissues were not significantly different between OVX mice and healthy mice. RNA sequencing demonstrated upregulation of ECMrelated genes, which might associate with the PI3K/AKT signaling pathway, in line with the results of microRNA analysis showing that mir-21, mir-29, mir-221, and let-7a were enriched in Wharton's jelly-MSC-EVs and correlated to the BMP and PI3K/AKT signaling pathways. Conclusion:The therapeutic effect of exogenous WJ-MSC-EVs in the treatment of osteoporosis was successfully assessed by a multiplexed molecular imaging strategy. The RNA sequencing demonstrated the possible molecular targets in the regulation of bone remodeling. The results highlight the novelty of diagnostic and therapeutic strategies of EV-based treatment for osteoporosis.

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Section: Discussionsupporting

confidence: 92%

Multiplexed Molecular Imaging Strategy Integrated with RNA Sequencing in the Assessment of the Therapeutic Effect of Wharton’s Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles for Osteoporosis

Lu¹,

Chen²,

Ke³

et al. 2021

IJN

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“…EVs from mouse vascular endothelial cells are enriched in miR-155, exhibiting protective effects on bone in an ovariectomized (OVX) mice model of menopausal osteoporosis [165]. The pro-osteogenic potential of EVs released by mouse MSCs was specifically addressed to the bone by linking the murine MSC-derived EVs with alendronate [166]. These bone-targeting EVs were effective in protecting bone of OVX mice.…”

Section: Discussionmentioning

confidence: 99%

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

Muraca

Cappariello

2020

IJMS

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Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates that non-coding RNAs can be shuttled among the cells and tissues via EVs, allowing non-coding RNAs to reach distant cells and exert systemic effects. Resident bone cells, including osteoclasts, osteoblasts, osteocytes, and endothelial cells, are tightly regulated by non-coding RNAs, and many of them can be exported from the cells to neighboring ones through EVs, triggering pathological conditions. For these reasons, researchers have also started to exploit EVs as a theranostic tool to address osteoporosis. In this review, we summarize some recent findings regarding the EVs’ involvement in the fine regulation of non-coding RNAs in the context of bone metabolism and osteoporosis.

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“…This allows EV surface functionalization for delivery of small molecules, large biomacromolecules, and polymers without altering particle size or function. Murine MSC-derived EVs were modified by copper-free click chemistry to generate an Ale-EVs system (EVs coupled with Alendronate, a medication used for osteoporosis) administered to an in vivo model of ovariectomy (OVX)-induced osteoporosis ( Wang Y. et al, 2020 ). These Ale-EVs had an affinity to bone tissue and promoted regeneration under osteoporotic conditions with low toxicity.…”

Section: Engineered Evsmentioning

confidence: 99%

“…In addition to cargo loading via surface conjugation ( Wang Y. et al, 2020 ), other strategies used to load cargo into EVs include parental cell modification, passive diffusion, and active loading. Overexpression of components in parental cells is an effective way to increase abundance in resulting EVs for greater function.…”

Section: Engineered Evsmentioning

confidence: 99%

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Claridge

Lozano

Poh

et al. 2021

Front. Cell Dev. Biol.

113

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Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields’ utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

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<p>Bone-Targeted Extracellular Vesicles from Mesenchymal Stem Cells for Osteoporosis Therapy</p>

Cited by 54 publications

References 56 publications

Multiplexed Molecular Imaging Strategy Integrated with RNA Sequencing in the Assessment of the Therapeutic Effect of Wharton’s Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles for Osteoporosis

Multiplexed Molecular Imaging Strategy Integrated with RNA Sequencing in the Assessment of the Therapeutic Effect of Wharton’s Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles for Osteoporosis

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

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