Use of ultrasound-targeted microbubble destruction to transfect IGF-1 cDNA to enhance the regeneration of rat wounded Achilles tendon in vivo

Tang, Yuanjiao; Leng, Qianying; Xiang, Xi; Zhang, L; Yang, Yujia; Qiu, Li

doi:10.1038/gt.2015.32

Cited by 19 publications

(17 citation statements)

References 24 publications

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“…Whether expression of transgenes will be switched off in patients would need careful evaluation when this treatment is moved to clinical trial in future, because immune responses is absent if human VEGF gene is introduced to the patients. A few recent studies highlighted non-viral or physical approaches to introduce genes to the Achilles tendon, an extrasynovial tendon 44 45 . Our group also used nanoparticles to deliver genes to tendons to inhibit adhesion formation 46 .…”

Section: Discussionmentioning

confidence: 99%

Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

Tang

Cao

et al. 2016

Sci Rep

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Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68–91% from week 2 after AAV2-bFGF treatment and by 82–210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion.

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Section: Discussionmentioning

confidence: 99%

Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

Tang

Cao

et al. 2016

Sci Rep

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“…For instance, IGF‐I can promote the proliferation and migration of fibroblasts in injured sites, contribute to the synthesis of collagen in T/L, and assist tissue healing (Hansen et al, 2013; Tang et al, 2015). Steinert et al (2008) used an adenoviral vector to transfer IFG‐1 cDNA to a collagen hydrogel to deliver genes in situ into the damaged ligament.…”

Section: Engineering Methodsmentioning

confidence: 99%

Injectable hydrogels for tendon and ligament tissue engineering

Liu

Zhang

Chen

2020

J Tissue Eng Regen Med

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The problem of tendon and ligament (T/L) regeneration in musculoskeletal diseases has long constituted a major challenge. In situ injection of formable biodegradable hydrogels, however, has been demonstrated to treat T/L injury and reduce patient suffering in a minimally invasive manner. An injectable hydrogel is more suitable than other biological materials due to the special physiological structure of T/L. Most other materials utilized to repair T/L are cell‐based, growth factor‐based materials, with few material properties. In addition, the mechanical property of the gel cannot reach the normal T/L level. This review summarizes advances in natural and synthetic polymeric injectable hydrogels for tissue engineering in T/L and presents prospects for injectable and biodegradable hydrogels for its treatment. In future T/L applications, it is necessary develop an injectable hydrogel with mechanics, tissue damage‐specific binding, and disease response. Simultaneously, the advantages of various biological materials must be combined in order to achieve personalized precision therapy.

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“…Studies demonstrated that UTMD could increase the expression of genes in the Achilles tendon [99][100][101]. For example, Tang et al transfected injured Achilles tendons of mice with insulin-like growth factor-1 (IGF-1) cDNA, showing that the maximum load, stiffness, and ultimate stress of treated Achilles tendons were higher than control group [102]. Bez et al transferred BMP-6 encoding DNA by UTMD in Yucatan mini-pigs, showing the significantly enhanced osteointegration of all pigs after 8 weeks [103].…”

Section: Musculoskeletal Diseasementioning

confidence: 99%

Recent Advances about Local Gene Delivery by Ultrasound

Chen¹,

Du²,

Yan³

2019

Gene Expression and Control

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Gene therapy has been widely explored as a pharmacological approach, with a great potential to treat various diseases. Generally, many diseases have definite lesion's site, especially for tumors. This feature results in a great demand on the delivery of therapeutic gene to the local lesion's site. Ultrasound combined with microbubbles provides a promising platform to deliver gene in a spatiotemporally controlled way. Ultrasound beam can be positioned and targeted onto the deepseated lesion's site of diseases by an external mobile transducer. Microbubbles can serve as vehicles for carrying genetic cargo and can be destructed by ultrasound, resulting in the local release of genetic payload. Meanwhile, sonoporation effect will occur upon which the bubbles are exposed to the appropriate ultrasonic energy, producing the transient small holes on the adjacent cell membrane and thus increasing the vascular and cellular permeability. In this chapter, we will review the recent advances about local gene delivery by ultrasound.

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Use of ultrasound-targeted microbubble destruction to transfect IGF-1 cDNA to enhance the regeneration of rat wounded Achilles tendon in vivo

Cited by 19 publications

References 24 publications

Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

Injectable hydrogels for tendon and ligament tissue engineering

Recent Advances about Local Gene Delivery by Ultrasound

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