Exosome-mimetics as an engineered gene-activated matrix induces in-situ vascularized osteogenesis

Zha, Yao; Lin, Tianyi; Li, Yawu; Zhang, Xin; Wang, Zihao; Li, Zubing; Ye, Yongqin; Wang, Bin; Zhang, Shengmin; Wang, Jianglin

doi:10.1016/j.biomaterials.2020.119985

Cited by 67 publications

(51 citation statements)

References 37 publications

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“…The mouse chondrogenic progenitor cell line, ATDC5, was purchased from BNCC (Suzhou, China). The ATDC5-derived exosomes were isolated and characterized as described before 17 . In brief, the serum-free medium of ATDC5 was centrifuged at 300×g for 15 min and 2000×g for 20 min at 4 °C to remove cellular debris.…”

Section: Methodsmentioning

confidence: 99%

“…The gene transfection of VEGF was observed via the expression of enhanced green fluorescence protein (EGFP), which was linked to the VEGF plasmid. Cell culture supernatants without the serum were collected to evaluate in vitro in HUVEC tube formation assays as previously reported 17 . In addition, qRT-PCR and ELISAs were performed to quantify the expression of VEGF as previously reported 17 .…”

Section: Methodsmentioning

confidence: 99%

“…Exosome-mediated acellular bone regeneration has been documented to enhance skull regeneration in our previously published work 17 . Herein, we continue to investigate the potential of exosome-enhanced therapy on large segmental bone defects that cannot be repaired without the promotion of bone cells and the reconstruction of internal vasculature.…”

Section: Introductionmentioning

confidence: 95%

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Progenitor cell-derived exosomes endowed with VEGF plasmids enhance osteogenic induction and vascular remodeling in large segmental bone defects

et al. 2021

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Large segmental bone regeneration remains a great challenge due to the lack of vascularization in newly formed bone. Conventional strategies primarily combine bone scaffolds with seed cells and growth factors to modulate osteogenesis and angiogenesis. Nevertheless, cell-based therapies have some intrinsic issues regarding immunogenicity, tumorigenesis, bioactivity and off-the-shelf transplantation. Exosomes are nano-sized (50-200 nm) extracellular vesicles with a complex composition of proteins, nucleic acids and lipids, which are attractive as therapeutic nanoparticles for disease treatment. Exosomes also have huge potential as desirable drug/gene delivery vectors in the field of regenerative medicine due to their excellent biocompatibility and efficient cellular internalization. Methods: We developed a cell-free tissue engineering system using functional exosomes in place of seed cells. Gene-activated engineered exosomes were constructed by using ATDC5-derived exosomes to encapsulate the VEGF gene. The specific exosomal anchor peptide CP05 acted as a flexible linker and effectively combined the engineered exosome nanoparticles with 3D-printed porous bone scaffolds. Results: Our findings demonstrated that engineered exosomes play dual roles as an osteogenic matrix to induce the osteogenic differentiation of mesenchymal stem cells and as a gene vector to controllably release the VEGF gene to remodel the vascular system. In vivo evaluation further verified that the engineered exosome-mediated bone scaffolds could effectively induce the bulk of vascularized bone regeneration. Conclusion: In our current work, we designed specifically engineered exosomes based on the requirements of vascularized bone repair in segmental bone defects. This work simultaneously illuminates the potential of functional exosomes in acellular tissue engineering.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Progenitor cell-derived exosomes endowed with VEGF plasmids enhance osteogenic induction and vascular remodeling in large segmental bone defects

et al. 2021

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“…Then the engineered exosome-mimetics was integrate into a biotin-avidin modified coaxial electrospun through covalent bonding. This well-designed, functional exosome-mimetics-mediated compound sustainably delivers the VEGF gene and significantly enhances osteogenesis and angiogenesis in a cranial defect model 139 . The potential therapeutic effects of exosomes provide a great opportunity for developing exosome-related biomedical applications in various fields along with chemical, cellular, and genetic engineering techniques.…”

Section: Exosome-based Therapeutics For Craniofacial and Dental Applimentioning

confidence: 99%

Emerging role of exosomes in craniofacial and dental applications

Xing¹,

Han²,

Li³

et al. 2020

Theranostics

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Exosomes, a specific subgroup of extracellular vesicles that are secreted by cells, have been recognized as important mediators of intercellular communication. They participate in a diverse range of physiological and pathological processes. Given the capability of exosomes to carry molecular cargos and transfer bioactive components, exosome-based disease diagnosis and therapeutics have been extensively studied over the past few decades. Herein, we highlight the emerging applications of exosomes as biomarkers and therapeutic agents in the craniofacial and dental field. Moreover, we discuss the current challenges and future perspectives of exosomes in clinical applications.

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“…In the past decade, exosomes have been used as a treatment strategy for ischemic stroke. 6 , 7 Exosomes are extracellular vesicles with a diameter of 30–100 nm that are secreted by all cell types and are able to cross the blood-brain barrier (BBB). 8 , 9 Exosomes contain various circular RNAs (circRNAs), proteins, mRNAs, and DNA that can function locally or be stably transferred to recipient cells.…”

Section: Introductionmentioning

confidence: 99%

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Chen

Wang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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The aim of the present study was to investigate the neuroprotective roles and mechanisms of the circular RNA circSHOC2 in ischemic-preconditioned astrocyte-derived exosomes (IPAS-EXOs) against ischemic stroke. We established an ischemia model based on oxygen glucose deprivation (OGD) in vitro and isolated resultant exosomes from astrocytes. Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Autophagy-related proteins were analyzed by western blotting. We found that exosomes derived from IPAS-preconditioned medium (IPAS-CM) exerted neuroprotection. Furthermore, circSHOC2 expression was significantly upregulated in exosomes released from IPAS-CM. Overexpression of circSHOC2 in neurons yielded the same protective effects as those from IPAS-EXOs in vitro , and similar results were also observed in the middle cerebral artery occlusion (MCAO) mouse model. Mechanistically, circSHOC2 reduced neuronal apoptosis via regulating autophagy. Furthermore, circSHOC2 was found to sponge miR-7670-3p, which regulated SIRT1 expression. Transfection with an miR-7670-3p small interfering RNA (siRNA) (siRNA-7670-3p) and incubation with circSHOC2 extracellular vesicles attenuated ischemia-induced neuronal apoptosis in vivo and in vitro , while silencing of SIRT1 reversed the protective effects of exosomal circSHOC2 on hypoxic cerebral neurons. Taken together, our findings indicate that circSHOC2 in IPAS-EXOs suppressed neuronal apoptosis and ameliorated neuronal damage by regulating autophagy and acting on the miR-7670-3p/SIRT1 axis, which might contribute to a therapeutic strategy for ischemic stroke treatment.

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Exosome-mimetics as an engineered gene-activated matrix induces in-situ vascularized osteogenesis

Cited by 67 publications

References 37 publications

Progenitor cell-derived exosomes endowed with VEGF plasmids enhance osteogenic induction and vascular remodeling in large segmental bone defects

Progenitor cell-derived exosomes endowed with VEGF plasmids enhance osteogenic induction and vascular remodeling in large segmental bone defects

Emerging role of exosomes in craniofacial and dental applications

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

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