The roles of TGF-β1 gene transfer on collagen formation during Achilles tendon healing

Hou, Yu; Mao, Zebing; Wei, Xuelei; Lin, Lin; Chen, Lianxu; Wang, Haijun; Fu, Xin; Zhang, JiYing; Yu, Chunxiao

doi:10.1016/j.bbrc.2009.03.159

Cited by 58 publications

(41 citation statements)

References 23 publications

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“…Like us, they found that TGF-β cDNA accelerated healing, based upon histology, collagen analysis and mechanical strength. In a subsequent study, the same group (Hou et al ., 2009b) confirmed that delivery of TGF-β cDNA promoted the synthesis of type I collagen and improved the ratio of type I to type III collagen. In these studies, TGF-β expression was detected up to 56 d. In the present study, TGF-β expression in transfected muscle was measured for a period of 7 d and might be increased beyond this time point.…”

Section: Discussionmentioning

confidence: 92%

“…Relevant genes include those encoding BMP-12 (Lou et al ., 2001; Majewski et al ., 2008), BMP-14/GDF-5 (Basile et al ., 2008; Bolt et al ., 2007; Rickert et al ., 2005), FGF-2 (Tang et al ., 2008), interleukin-10 (Ricchetti et al ., 2008), TGF-β1 (Hou et al ., 2009b), insulin-like growth factor-1 (Schnabel et al ., 2009), vascular endothelial growth factor (Hou et al ., 2009a), and PDGF (Suwalski et al ., 2010). Most such studies have used viral vectors for gene transfer because of their high efficiency.…”

Section: Introductionmentioning

confidence: 99%

“…Ex vivo delivery strategies often use mesenchymal stem cells (MSCs) as vehicles (Hou et al ., 2009a; Hou et al ., 2009b; Schnabel et al ., 2009), but in a clinical setting such manipulations are cumbersome, expensive and invasive. In response to these considerations, we have been interested in developing expedited ex vivo gene delivery technologies that can be accomplished conveniently in a single operative session (Evans et al ., 2007).…”

Section: Introductionmentioning

confidence: 99%

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Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA

Majewski

Porter

Betz

et al. 2012

eCM

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Tendon rupture is a common injury. Inadequate endogenous repair often leaves patients symptomatic, with tendons susceptible to re-rupture. Administration of certain growth factors improves tendon healing in animal models, but their delivery remains a challenge. Here we evaluated the delivery of TGF-β1 to tendon defects by the implantation of genetically modifi ed muscle grafts. Rat muscle biopsies were transduced with recombinant adenovirus encoding TGF-β1 and grafted onto surgically transected Achilles tendons in recipient animals. Tissue regenerates were compared to those of controls by biomechanical testing as well as histochemical and immunohistochemical analyses. Healing was greatly accelerated when genetically modifi ed grafts were implanted into tendon defects, with the resulting repair tissue gaining nearly normal histological appearance as early as 2 weeks postoperatively. This was associated with decreased deposition of type III collagen in favour of large fi bre bundles indicative of type I collagen. These differences in tendon composition coincided with accelerated restoration of mechanical strength. Tendon thickness increased in gene-treated animals at weeks 1 and 2, but by week 8 became signifi cantly lower than that of controls suggesting accelerated remodelling. Thus localised TGF-β1 delivery via adenovirus-modifi ed muscle grafts improved tendon healing in this rat model and holds promise for clinical application.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA

Majewski

Porter

Betz

et al. 2012

eCM

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“…The local administration of VEGF improves tendon revascularization, but not graft mechanics [34, 68]. TGF- β 1 promotes improved strength in Achilles tendon regeneration by regulating collagen I and III synthesis, cross-link formation, and matrix remodeling [69]. …”

Section: Gene Therapymentioning

confidence: 99%

Stem Cell Applications in Tendon Disorders: A Clinical Perspective

Young

2012

Stem Cells International

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Tendon injuries are a common cause of morbidity and a significant health burden on society. Tendons are structural tissues connecting muscle to bone and are prone to tearing and tendinopathy, an overuse or degenerative condition that is characterized by failed healing and cellular depletion. Current treatments, for tendon tear are conservative, surgical repair or surgical scaffold reconstruction. Tendinopathy is treated by exercises, injection therapies, shock wave treatments or surgical tendon debridement. However, tendons usually heal with fibrosis and scar tissue, which has suboptimal tensile strength and is prone to reinjury, resulting in lifestyle changes with activity restriction. Preclinical studies show that cell therapies have the potential to regenerate rather than repair tendon tissue, a process termed tenogenesis. A number of different cell lines, with varying degrees of differentiation, have being evaluated including stem cells, tendon derived cells and dermal fibroblasts. Even though cellular therapies offer some potential in treating tendon disorders, there have been few published clinical trials to determine the ideal cell source, the number of cells to administer, or the optimal bioscaffold for clinical use.

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“…Collagen fibers are largely responsible for the mechanical strength of the healing tendon making treatment with TGF-β an important area of investigation [30]. Treatment with TGF-beta1 cDNA-transduced BMSCs grafts, injections of TGF-β, and delivery of TGF-β by adenovirus-modified muscle grafts have shown promising results in rat Achilles tendon models [47,35,29].…”

Section: Hepatocyte Growth Factormentioning

confidence: 99%

Biologics in Achilles tendon healing and repair: a review

Shapiro

Grande

Drakos

2015

Curr Rev Musculoskelet Med

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Injuries of the Achilles tendon are relatively common with potentially devastating outcomes. Healing Achilles tendons form a fibrovascular scar resulting in a tendon which may be mechanically weaker than the native tendon. The resulting strength deficit causes a high risk for reinjury and other complications. Treatments using biologics aim to restore the normal properties of the native tendon and reduce the risk of rerupture and maximize tendon function. The purpose of this review was to summarize the current findings of various therapies using biologics in an attempt to improve the prognosis of Achilles tendon ruptures and tendinopathies. A

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The roles of TGF-β1 gene transfer on collagen formation during Achilles tendon healing

Cited by 58 publications

References 23 publications

Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA

Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA

Stem Cell Applications in Tendon Disorders: A Clinical Perspective

Biologics in Achilles tendon healing and repair: a review

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