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Effect of P144® (Anti-TGF-β) in an "In Vivo" Human Hypertrophic Scar Model in Nude Mice.

Qiu SS, Dotor J, Hontanilla B - PLoS ONE (2015)

Bottom Line: Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1).Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups.Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic and Reconstructive Surgery, Clínica Universidad de Navarra, Pamplona, Spain.

ABSTRACT

Background: Hypertrophic scars are one of the most important complications in surgery due to their cosmetic and functional impairments. Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1). The aim of the current study was to determine the clinical effect of the inhibition of TGF-β1 signaling in human hypertrophic scars implanted in nude mice by topical application of an inhibitor of TGF-β1 (P144®).

Material and methods: A total of 30 human hypertrophic scars were implanted in 60 nude mice. The animals were divided in two groups, group A (placebo) and group B (treatment). Group C (basal) was considered as the preimplanted scar samples and they were not implanted in the nude mice. After the shedding period, topical application of a lipogel containing placebo (group A) or P144 (group B) was daily administered during two weeks. The animals were sacrificed upon completion of the study. Total area, thickness and collagen fibers area were measure and compared across all groups. Immunohistochemistry was also performed in order to quantify collagen type I and type III and elastic fiber expressions present in the dermis.

Results: Successful shedding was achieved in 83,3% of the xenografts. The mean time for shedding was 35±5.4 days. Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups. Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group.

Conclusion: Topical application of an inhibitor of TGF-β1 may promote scar maturation and clinical improvement of hypertrophic scar morphology features in an "in vivo" model in nude mice after two weeks of treatment.

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Macroscopic aspect of a hypertrophic scar in a nude mouse.A. Characteristic stiffness of a human hypertrophic scars after 35 days. B. After sacrificing the animal, vessels can be seen coming from the surrounding tissue arrived to nourish the hypertrophic scar.
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pone.0144489.g001: Macroscopic aspect of a hypertrophic scar in a nude mouse.A. Characteristic stiffness of a human hypertrophic scars after 35 days. B. After sacrificing the animal, vessels can be seen coming from the surrounding tissue arrived to nourish the hypertrophic scar.

Mentions: After completion of grafts healing period, 50 out of 60 grafts were successfully shed (83.33%). Seven mice died likely due to an infection during the post-grafting period. The rest of the animals were sacrificed using cervical dislocation. Five placebo cases developed host vs. graft reaction secondary to surgical sutures. A total of 36 mice (18 pairs) were suitable for testing of P144® effect compared with placebo. The mean time of shedding was 35±5.4 days. Xenografts were shed with the characteristic stiffness of a human hypertrophic scar, elevated, thickened and confined to the site of implantation. Dense collagen bundles confined in the reticular dermis, with absent of human skin appendages confirmed the presence of hypertrophic scarring. Neovascularization could be seen macroscopically as small vessels reaching the grafts from the surrounding tissue of the host. (Fig 1)


Effect of P144® (Anti-TGF-β) in an "In Vivo" Human Hypertrophic Scar Model in Nude Mice.

Qiu SS, Dotor J, Hontanilla B - PLoS ONE (2015)

Macroscopic aspect of a hypertrophic scar in a nude mouse.A. Characteristic stiffness of a human hypertrophic scars after 35 days. B. After sacrificing the animal, vessels can be seen coming from the surrounding tissue arrived to nourish the hypertrophic scar.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697841&req=5

pone.0144489.g001: Macroscopic aspect of a hypertrophic scar in a nude mouse.A. Characteristic stiffness of a human hypertrophic scars after 35 days. B. After sacrificing the animal, vessels can be seen coming from the surrounding tissue arrived to nourish the hypertrophic scar.
Mentions: After completion of grafts healing period, 50 out of 60 grafts were successfully shed (83.33%). Seven mice died likely due to an infection during the post-grafting period. The rest of the animals were sacrificed using cervical dislocation. Five placebo cases developed host vs. graft reaction secondary to surgical sutures. A total of 36 mice (18 pairs) were suitable for testing of P144® effect compared with placebo. The mean time of shedding was 35±5.4 days. Xenografts were shed with the characteristic stiffness of a human hypertrophic scar, elevated, thickened and confined to the site of implantation. Dense collagen bundles confined in the reticular dermis, with absent of human skin appendages confirmed the presence of hypertrophic scarring. Neovascularization could be seen macroscopically as small vessels reaching the grafts from the surrounding tissue of the host. (Fig 1)

Bottom Line: Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1).Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups.Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic and Reconstructive Surgery, Clínica Universidad de Navarra, Pamplona, Spain.

ABSTRACT

Background: Hypertrophic scars are one of the most important complications in surgery due to their cosmetic and functional impairments. Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1). The aim of the current study was to determine the clinical effect of the inhibition of TGF-β1 signaling in human hypertrophic scars implanted in nude mice by topical application of an inhibitor of TGF-β1 (P144®).

Material and methods: A total of 30 human hypertrophic scars were implanted in 60 nude mice. The animals were divided in two groups, group A (placebo) and group B (treatment). Group C (basal) was considered as the preimplanted scar samples and they were not implanted in the nude mice. After the shedding period, topical application of a lipogel containing placebo (group A) or P144 (group B) was daily administered during two weeks. The animals were sacrificed upon completion of the study. Total area, thickness and collagen fibers area were measure and compared across all groups. Immunohistochemistry was also performed in order to quantify collagen type I and type III and elastic fiber expressions present in the dermis.

Results: Successful shedding was achieved in 83,3% of the xenografts. The mean time for shedding was 35±5.4 days. Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups. Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group.

Conclusion: Topical application of an inhibitor of TGF-β1 may promote scar maturation and clinical improvement of hypertrophic scar morphology features in an "in vivo" model in nude mice after two weeks of treatment.

Show MeSH
Related in: MedlinePlus