Effect of rAAV2-hTGFβ1 Gene Transfer on Matrix Synthesis in an In Vivo Rabbit Disk Degeneration Model

Liu, Haifei; Ning, Bin; Zhang, Han; Wang, Dechun; Hu, Yanling; Qiao, Guangxi; Zhao, Yunpeng; Hu, Yang

doi:10.1097/bsd.0b013e3182a26553

Cited by 8 publications

(10 citation statements)

References 15 publications

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“…The AAV vector is well suited for gene transfer in vivo due to its low immunogenicity and high safety. 34 , 35 The observed rapid and prolonged upregulation of protein expression and increased matrix synthesis indicated that AAV-mediated therapeutic gene transfer could be a promising treatment for IDD in vivo . 34 Another study showed that AAV-mediated BMP-7 and SOX9 cotransfection in vitro can promote the synthesis of collagen II in NPCs in a human-degenerative intervertebral disc.…”

Section: Discussionmentioning

confidence: 99%

“… 34 , 35 The observed rapid and prolonged upregulation of protein expression and increased matrix synthesis indicated that AAV-mediated therapeutic gene transfer could be a promising treatment for IDD in vivo . 34 Another study showed that AAV-mediated BMP-7 and SOX9 cotransfection in vitro can promote the synthesis of collagen II in NPCs in a human-degenerative intervertebral disc. 36 In this study, a degenerative spine model in rats was generated by acupuncture of the intervertebral disc, and AAV-2 carrying specific genes was injected into rat intervertebral disc tissue.…”

Section: Discussionmentioning

confidence: 99%

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Exosome-Transported circRNA_0000253 Competitively Adsorbs MicroRNA-141-5p and Increases IDD

Song

Chen

Zheng

et al. 2020

Molecular Therapy - Nucleic Acids

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The pathogenesis of intervertebral disc degeneration (IDD) is complex, and a better understanding of IDD pathogenesis may provide a better method for the treatment of IDD. Exosomes are 40–100 nm nanosized vesicles that are released from many cell types into the extracellular space. We speculated that exosome-transported circular RNAs (circRNAs) could regulate IDD. Exosomes from different degenerative grades were isolated and added to nucleus pulposus cells (NPCs), and indicators of proliferation and apoptosis were detected. Based on the previous circRNA microarray results, the top 10 circRNAs were selected. PCR was performed to determine the circRNA with the maximum upregulation. Competing endogenous RNA (ceRNA) analysis was carried out, and the sponged microRNA (miRNA) was identified. Further functional verification of the selected circRNA was carried out in vivo and in vitro . NPCs of different degenerative grades secreted exosomes, which could regulate IDD. circRNA_0000253 was selected as having the maximum upregulation in degenerative NPC exosomes. ceRNA analysis showed that circRNA_0000253 could adsorb miRNA-141-5p to downregulate SIRT1. circRNA_0000253 was confirmed to increase IDD by adsorbing miRNA-141-5p and downregulating SIRT1 in vivo and in vitro . Exosomal circRNA_0000253 owns the maximum upregulation in degenerative NPC exosomes and could promote IDD by adsorbing miRNA-141-5p and downregulating SIRT1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exosome-Transported circRNA_0000253 Competitively Adsorbs MicroRNA-141-5p and Increases IDD

Song

Chen

Zheng

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Different animal models of disc degeneration have been used for regenerative approaches of cell transplantation and gene therapy with applications of bioactive factors and bioscaffolds. 40…”

Section: Introductionmentioning

confidence: 99%

“…In vivo gene therapeutic approaches have been presented in different animal models of disc degeneration by using retrovirus, lentivirus (LV), adenovirus, and adeno-associated virus (AAV) gene delivery vectors. 53–58,83–89,107,110,136,139,148 Viral vector-based gene therapeutic treatments of DDD can be performed: (I) by direct injection of viral vectors into degenerative IVDs leading to the expression of the therapeutic gene by disc cells transduced within the IVDs; (II) by injection of genetically modified cells into degenerative IVDs that are able to express the therapeutic gene in vivo ; and (III) by transplanting bioscaffolds that are seeded with genetically modified cells enabling the in vivo expression of the therapeutic gene. Biological treatment approaches of DDD are schematically illustrated in Figure 3.…”

Section: Introductionmentioning

confidence: 99%

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Animal models of regenerative medicine for biological treatment approaches of degenerative disc diseases

Mern

Walsen

Beierfuß

et al. 2020

Exp Biol Med (Maywood)

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Degenerative disc disease (DDD) is a painful, chronic and progressive disease, which is characterized by inflammation, structural and biological deterioration of the intervertebral disc (IVD) tissues. DDD is specified as cell-, age-, and genetic-dependent degenerative process that can be accelerated by environmental factors. It is one of the major causes of chronic back pain and disability affecting millions of people globally. Current treatment options, such as physical rehabilitation, pain management, and surgical intervention, can provide only temporary pain relief. Different animal models have been used to study the process of IVD degeneration and develop therapeutic options that may restore the structure and function of degenerative discs. Several research works have depicted considerable progress in understanding the biological basis of disc degeneration and the therapeutic potentials of cell transplantation, gene therapy, applications of supporting biomaterials and bioactive factors, or a combination thereof. Since animal models play increasingly significant roles in treatment approaches of DDD, we conducted an electronic database search on Medline through June 2020 to identify, compare, and discuss publications regarding biological therapeutic approaches of DDD that based on intradiscal treatment strategies. We provide an up-to-date overview of biological treatment strategies in animal models including mouse, rat, rabbit, porcine, bovine, ovine, caprine, canine, and primate models. Although no animal model could profoundly reproduce the clinical conditions in humans; animal models have played important roles in specifying our knowledge about the pathophysiology of DDD. They are crucial for developing new therapy approaches for clinical applications.

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Tissue engineering for regeneration and replacement of the intervertebral disk

Sloan

Farhang

Stover

et al. 2020

Principles of Tissue Engineering

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Effect of rAAV2-hTGFβ1 Gene Transfer on Matrix Synthesis in an In Vivo Rabbit Disk Degeneration Model

Cited by 8 publications

References 15 publications

Exosome-Transported circRNA_0000253 Competitively Adsorbs MicroRNA-141-5p and Increases IDD

Exosome-Transported circRNA_0000253 Competitively Adsorbs MicroRNA-141-5p and Increases IDD

Animal models of regenerative medicine for biological treatment approaches of degenerative disc diseases

Tissue engineering for regeneration and replacement of the intervertebral disk

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