Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss

Yan, Hu; Li, Xiaoqun; Zhang, Qin; Gu, Zhifeng; Luo, Ying; Guo, Jiawei; Wang, Xiuhui; Jing, Yingying; Chen, Xiao; Su, Jiacan

doi:10.1016/j.bioactmat.2021.02.014

Cited by 132 publications

(107 citation statements)

References 48 publications

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“…Luo et al reported an aptamer-functionalized MSC-derived exosome for osteoporosis treatment [ 57 ]. Hu et al constructed hybrid nanoparticles based on C-X-C motif chemokine receptor 4 (CXCR4)-positive exosomes [ 58 ], which took advantage of mechanism involved in the CXCR4 + cells homing to implement bone-targeted drug delivery. However, these results only showed the increased bone accumulation rather than delivery to specific bone cells in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…However, these results only showed the increased bone accumulation rather than delivery to specific bone cells in vivo . In addition to this, most published studies [ 19 , 20 , 58 ] about exosomes for bone regeneration or osteoporosis treatment only showed single mechanism while the BT-Exo-si Shn3 showed synergistic and comprehensive anti-osteoporosis effects including enhanced osteogenic differentiation, promoted type H vessel formation and inhibited osteoclast formation. Furthermore, most studies [ 57 , 58 ] reported that the effect of exosomes loading siRNA has depended on the siRNA cargo while the exosomes only acted as carriers.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to this, most published studies [ 19 , 20 , 58 ] about exosomes for bone regeneration or osteoporosis treatment only showed single mechanism while the BT-Exo-si Shn3 showed synergistic and comprehensive anti-osteoporosis effects including enhanced osteogenic differentiation, promoted type H vessel formation and inhibited osteoclast formation. Furthermore, most studies [ 57 , 58 ] reported that the effect of exosomes loading siRNA has depended on the siRNA cargo while the exosomes only acted as carriers. In contrast, the BT-Exo-si Shn3 took advantage of the intrinsic anti-osteoporosis effects of iMSC-derived exosomes and collaborated with the loaded siRNA to enhance the efficacy.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

Cui

Guo

Kong

et al. 2022

Bioactive Materials

106

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The complex pathogenesis of osteoporosis includes excessive bone resorption, insufficient bone formation and inadequate vascularization, a combination which is difficult to completely address with conventional therapies. Engineered exosomes carrying curative molecules show promise as alternative osteoporosis therapies, but depend on specifically-functionalized vesicles and appropriate engineering strategies. Here, we developed an exosome delivery system based on exosomes secreted by mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (iPSCs). The engineered exosomes BT-Exo-si Shn3 , took advantage of the intrinsic anti-osteoporosis function of these special MSC-derived exosomes and collaborated with the loaded siRNA of the Shn3 gene to enhance the therapeutic effects. Modification of a bone-targeting peptide endowed the BT-Exo-si Shn3 an ability to deliver siRNA to osteoblasts specifically. Silencing of the osteoblastic Shn3 gene enhanced osteogenic differentiation, decreased autologous RANKL expression and thereby inhibited osteoclast formation. Furthermore, Shn3 gene silencing increased production of SLIT3 and consequently facilitated vascularization, especially formation of type H vessels. Our study demonstrated that BT-Exo-si Shn3 could serve as a promising therapy to kill three birds with one stone and implement comprehensive anti-osteoporosis effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

Cui

Guo

Kong

et al. 2022

Bioactive Materials

106

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“…Hu et al also found that the C-X-C motif chemokine receptor 4 (CXCR4)-modified exosomes acquired bone-targeting function. CXCR4-modified exosomes and liposomes that released antagomir-188, which has bone forming and adipogenesis inhibition abilities, were fused to treat osteoporosis [ 69 ].…”

Section: Exosomesmentioning

confidence: 99%

Advances in the application of mesenchymal stem cells, exosomes, biomimetic materials, and 3D printing in osteoporosis treatment

Lin

et al. 2021

Cell Mol Biol Lett

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Owing to an increase in the aging population, osteoporosis has become a severe public health concern, with a high prevalence among the elderly and postmenopausal adults. Osteoporosis-related fracture is a major cause of morbidity and mortality in elderly and postmenopausal adults, posing a considerable socioeconomic burden. However, existing treatments can only slow down the process of osteoporosis, reduce the risk of fractures, and repair fractures locally. Therefore, emerging methods for treating osteoporosis, such as mesenchymal stem cell transplantation, exosome-driving drug delivery systems, biomimetic materials, and 3D printing technology, have received increasing research attention, with significant progress. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can differentiate into different types of functional cells. Exosomes play a key role in regulating cell microenvironments through paracrine mechanisms. Bionic materials and 3D printed scaffolds are beneficial for the reconstruction and repair of osteoporotic bones and osteoporosis-related fractures. Stem cells, exosomes, and biomimetic materials represent emerging technologies for osteoporosis treatment. This review summarizes the latest developments in these three aspects.

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“…Moreover, exos are adept at delivering their contents to specific acceptor cells. For instance, exos released by fibroblasts (NIH-3T3 cells) are capable of delivering antagomir-188 to mesenchymal stem cells (MSCs) in a bone-targeted manner [51]. Moreover, MSC-derived exos can promote angiogenesis and osteogenesis by delivering exosomal miR-29a [52].…”

Section: Exosomes (Exos) and Exo-associated Mirnasmentioning

confidence: 99%

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

Lü

Zhang

Liang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Osteoporosis (OP) is an aging-related disease involving permanent bone tissue atrophy. Most patients with OP show high levels of oxidative stress (OS), which destroys the microstructure of bone tissue and promotes disease progression. Exosomes (exos) help in the delivery of microRNAs (miRNAs) and allow intercellular communication. In OP, exosomal miRNAs modulate several physiological processes, including the OS response. In the present review, we aim to describe how exosomal miRNAs and OS contribute to OP. We first summarize the relationship of OS with OP and then detail the features of exos along with the functions of exo-related miRNAs. Further, we explore the interplay between exosomal miRNAs and OS in OP and summarize the functional role of exos in OP. Finally, we identify the advantages of exo-based miRNA delivery in treatment strategies for OP. Our review seeks to improve the current understanding of the mechanism underlying OP pathogenesis and lay the foundation for the development of novel theranostic approaches for OP.

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Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss

Cited by 132 publications

References 48 publications

A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

Advances in the application of mesenchymal stem cells, exosomes, biomimetic materials, and 3D printing in osteoporosis treatment

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

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