Transforming Growth Factor β3 (TGFβ3) Accelerates Wound Healing Without Alteration of Scar Prominence

Wu, Liancun; Siddiqui, Aamir; Morris, David E.; Cox, David A.; Roth, Sanford I.; Mustoe, Thomas A.

doi:10.1001/archsurg.1997.01430310067014

Cited by 94 publications

(23 citation statements)

References 32 publications

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“…However, to date, no regular 2D cell culture model has been able to show a significant difference in function between T1 and T3 (Guo et al, 2016; Wu et al, 1997). Therefore, to examine the difference in T1 and T3’s effect on the expression of SMA, we developed a 3D cell culture model, in which the cells secrete and interact with their own ECM, adding another layer of complexity to regular cell culture experiments.…”

Section: Discussionmentioning

confidence: 99%

Development of wound healing models to study TGFβ3's effect on SMA

Sriram

Tran

Guo

et al. 2017

Experimental Eye Research

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The goal of this study was to test the efficacy of transforming growth factor beta 3 (TGFβ3) in reducing α- smooth muscle actin (SMA) expression in two models—an ex vivo organ culture and an in vitro 3D cell construct—both of which closely mimic an in vivo environment. For the ex vivo organ culture system, a central 6.0 mm corneal keratectomy was performed on freshly excised rabbit globes The corneas were then excised, segregated into groups treated with 1.0 ng/ml TGFβ1 or β3 (T1 or T3, respectively), and cultured for 2 weeks. The corneas were assessed for levels of haze and analyzed for SMA mRNA levels. For the 3D in vitro model, rabbit corneal fibroblasts (RbCFs) were cultured for 4 weeks on poly-transwell membranes in Eagle’s minimum essential media (EMEM) + 10% FBS + 0.5 mM vitamin C ± 0.1 ng/ml T1 or T3. At the end of 4 weeks, the constructs were processed for analysis by indirect-immunofluorescence (IF) and RT-qPCR. The RT-qPCR data showed that SMA mRNA expression in T3 samples for both models was significantly lower (p < 0.05) than T1 treatment (around 3-fold in ex vivo and 2-fold in constructs). T3 also reduced the amount of scarring in ex vivo corneas as compared with the T1 samples. IF data from RbCF constructs confirmed that T3-treated samples had up to 4-fold (p < 0.05) lower levels of SMA protein expression than samples treated with T1. These results show that T3 when compared to T1 decreases the expression of SMA in both ex vivo organ culture and in vitro 3D cell construct models. Understanding the mechanism of T3’s action in these systems and how they differ from simple cell culture models, may potentially help in developing T3 as an anti-scarring therapy.

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Section: Discussionmentioning

confidence: 99%

Development of wound healing models to study TGFβ3's effect on SMA

Sriram

Tran

Guo

et al. 2017

Experimental Eye Research

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“…Sato et al (2003) have shown that decorin can prevent TGFβ1-induced muscle fibrosis but perhaps the most successful mediator of the effects of TGFβ1 has been the application of TGFβ3 (Ghosh et al 2006;Hosokawa et al 2003;Occleston et al 2009;Wu et al 1997). While TGFβ3 has not been shown to have direct effects on muscle repair, extensive research has shown TGFβ3 to be a potent inhibitor of scar tissue formation reducing the influx of inflammatory cells to the wound site without delaying wound healing (Wu et al 1997). The indirect effects of inhibiting TGFβ1 could plausibly result in enhanced progenitor cell proliferation, differentiation and recruitment, while decreasing scar tissue.…”

Section: Control Of the Regenerative Microenvironmentmentioning

confidence: 99%

Regeneration of skeletal muscle

2011

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Skeletal muscle has a robust capacity for regeneration following injury. However, few if any effective therapeutic options for volumetric muscle loss are available. Autologous muscle grafts or muscle transposition represent possible salvage procedures for the restoration of mass and function but these approaches have limited success and are plagued by associated donor site morbidity. Cell-based therapies are in their infancy and, to date, have largely focused on hereditary disorders such as Duchenne muscular dystrophy. An unequivocal need exists for regenerative medicine strategies that can enhance or induce de novo formation of functional skeletal muscle as a treatment for congenital absence or traumatic loss of tissue. In this review, the three stages of skeletal muscle regeneration and the potential pitfalls in the development of regenerative medicine strategies for the restoration of functional skeletal muscle in situ are discussed.

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“…Topical TGF-β1 stimulates wound repair in young ischaemic rabbit skin, but not in aged skin 80 . It does this in young rabbits by increasing the rate of granulation tissue formation, but without altering scar prominence 81 . There have been no reported trials using TGF-β in human wound healing, probably owing to the complexity of its actions and interactions, together with concern about neoplastic transformation of cells.…”

Section: Transforming Growth Factor βmentioning

confidence: 99%

Growth factors in the treatment of diabetic foot ulcers

Bennett

Griffiths

Schor

et al. 2003

British Journal of Surgery

287

208

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There has been a generally disappointing clinical outcome from growth factor trials, although topical platelet-derived growth factor has shown significant benefit and should be considered in non-healing, well perfused ulcers after failure of conventional wound care. The modulatory role of the extracellular matrix in the cellular response to growth factors and data from regenerative-type fetal wound healing are further areas of interest. The chemical induction of microvessel formation may become a future therapeutic option.

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Transforming Growth Factor β3 (TGFβ3) Accelerates Wound Healing Without Alteration of Scar Prominence

Cited by 94 publications

References 32 publications

Development of wound healing models to study TGFβ3's effect on SMA

Development of wound healing models to study TGFβ3's effect on SMA

Regeneration of skeletal muscle

Growth factors in the treatment of diabetic foot ulcers

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