A New TGF-β Mimetic, XEP™-716 Miniprotein™, Exhibiting Regenerative Properties Objectivized by Instrumental Evaluation

IF 3.5 3区 医学 Q1 DERMATOLOGY
Hanane Chajra, Thibaut Saguet, Corinne Granger, Lionel Breton, Pedro Contreiras Pinto, Mickael Machicoane, Jean Marc Le Doussal
{"title":"A New TGF-β Mimetic, XEP™-716 Miniprotein™, Exhibiting Regenerative Properties Objectivized by Instrumental Evaluation","authors":"Hanane Chajra, Thibaut Saguet, Corinne Granger, Lionel Breton, Pedro Contreiras Pinto, Mickael Machicoane, Jean Marc Le Doussal","doi":"10.1007/s13555-024-01273-2","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations. Our objective was to demonstrate the rejuvenating effects of XEP™-716 Miniprotein™ on skin, a miniprotein having TGF-β beta-like properties, in vitro on normal human fibroblasts and at the clinical level.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In vitro, the skin rejuvenation properties of XEP™-716 Miniprotein™ were studied by quantification of well-known dermal components such as collagen type I, hyaluronic acid and elastin. At the clinical level, we used a non-invasive technique, the confocal laser scanning microscopy (CLSM) system, which enabled non-invasive morphological characterization of skin structures (stratum corneum thickness, viable epidermis, full epidermis, dermal-epidermal junction, papillae, dermal collagen density) and high-frequency ultrasonography to quantify the dermal density and thickness, which are useful parameters for quantifying rejuvenating effects on skin. Lastly, a cutometer was used to assess the skin's biomechanical properties, mainly firmness and elasticity. This monocentric double-blind, split-face, randomized, placebo-controlled clinical trial compared the active ingredient XEP™-716 Miniprotein™ in a vehicle on one hemiface versus vehicle alone on the other (placebo) and enrolled panelists aged 40 to 60 years old. All measurements were carried out on the malar area before and after 28 and 56 days of twice daily application of a cosmetic cream formulation containing either 2.5% or 5% XEP™-716 Miniprotein™. The skin rejuvenating properties were demonstrated by studying dermo-epidermal junction (DEJ) flattening reduction using the measure of two parameters by CLSM: the DEJ length and number of edged papillae. Dermis rejuvenation was assessed by measuring the collagen fiber perimeters (CLSM), dermal density and dermal thickness (ultrasonography).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The in vitro results confirmed the ability of XEP™-716 Miniprotein™ to stimulate the key extracellular macromolecules, namely collagen type I, hyaluronic acid and elastin, at a level comparable to that induced by TGF beta growth factor. The clinical data showed that after 28 and 56 days of topical XEP™-716 Miniprotein™ application, there was a statistically significant increase of DEJ length, number of edged papillae and collagen fiber perimeters. At the same time point, the B-scan images of facial skin showed a statistically significant increase of dermal density and thickness. These results reveal that the DEJ became more undulated and tightly attached to the dermis, while the papillary dermis was densified, both traits being typical characteristic of younger skin. Rejuvenation was also confirmed by an improvement of skin firmness and elasticity.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The in vitro and clinical results presented in this article show that XEP™-716 Miniprotein™ is a potent ingredient to rejuvenate the DEJ and dermis of mature skin.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":"15 1","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dermatology and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13555-024-01273-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction

Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations. Our objective was to demonstrate the rejuvenating effects of XEP™-716 Miniprotein™ on skin, a miniprotein having TGF-β beta-like properties, in vitro on normal human fibroblasts and at the clinical level.

Methods

In vitro, the skin rejuvenation properties of XEP™-716 Miniprotein™ were studied by quantification of well-known dermal components such as collagen type I, hyaluronic acid and elastin. At the clinical level, we used a non-invasive technique, the confocal laser scanning microscopy (CLSM) system, which enabled non-invasive morphological characterization of skin structures (stratum corneum thickness, viable epidermis, full epidermis, dermal-epidermal junction, papillae, dermal collagen density) and high-frequency ultrasonography to quantify the dermal density and thickness, which are useful parameters for quantifying rejuvenating effects on skin. Lastly, a cutometer was used to assess the skin's biomechanical properties, mainly firmness and elasticity. This monocentric double-blind, split-face, randomized, placebo-controlled clinical trial compared the active ingredient XEP™-716 Miniprotein™ in a vehicle on one hemiface versus vehicle alone on the other (placebo) and enrolled panelists aged 40 to 60 years old. All measurements were carried out on the malar area before and after 28 and 56 days of twice daily application of a cosmetic cream formulation containing either 2.5% or 5% XEP™-716 Miniprotein™. The skin rejuvenating properties were demonstrated by studying dermo-epidermal junction (DEJ) flattening reduction using the measure of two parameters by CLSM: the DEJ length and number of edged papillae. Dermis rejuvenation was assessed by measuring the collagen fiber perimeters (CLSM), dermal density and dermal thickness (ultrasonography).

Results

The in vitro results confirmed the ability of XEP™-716 Miniprotein™ to stimulate the key extracellular macromolecules, namely collagen type I, hyaluronic acid and elastin, at a level comparable to that induced by TGF beta growth factor. The clinical data showed that after 28 and 56 days of topical XEP™-716 Miniprotein™ application, there was a statistically significant increase of DEJ length, number of edged papillae and collagen fiber perimeters. At the same time point, the B-scan images of facial skin showed a statistically significant increase of dermal density and thickness. These results reveal that the DEJ became more undulated and tightly attached to the dermis, while the papillary dermis was densified, both traits being typical characteristic of younger skin. Rejuvenation was also confirmed by an improvement of skin firmness and elasticity.

Conclusion

The in vitro and clinical results presented in this article show that XEP™-716 Miniprotein™ is a potent ingredient to rejuvenate the DEJ and dermis of mature skin.

Abstract Image

一种新型 TGF-β 拟态物质 XEP™-716 Miniprotein™,通过仪器评估显示出客观的再生特性
导言:皮肤老化是内在和外在因素共同作用的结果,在宏观层面上表现为皮肤粗糙、不平整和起皱。在微观层面上,衰老表现为角质细胞更替减少、真皮-表皮交界处变平以及胶原纤维密度降低;然而,使用皮肤活检来评估这些微观变化的特征特性对专家小组成员来说限制太多,很少使用。非侵入性技术的发展为此类评估提供了机会。我们的目标是在体外正常人成纤维细胞和临床层面上证明 XEP™-716 Miniprotein™ 对皮肤的嫩肤效果,它是一种具有 TGF-β 类似特性的微型蛋白。方法在体外,我们通过量化 I 型胶原蛋白、透明质酸和弹性蛋白等众所周知的真皮成分来研究 XEP™-716 Miniprotein™ 的嫩肤特性。在临床层面,我们使用了一种非侵入性技术--共焦激光扫描显微镜(CLSM)系统,该系统可对皮肤结构(角质层厚度、存活表皮、完整表皮、真皮-表皮交界处、乳头、真皮胶原蛋白密度)进行非侵入性形态学表征,并使用高频超声波成像技术对真皮密度和厚度进行量化,这些都是量化皮肤年轻化效果的有用参数。最后,使用切口计评估皮肤的生物力学特性,主要是紧致度和弹性。这项单中心、双盲、分面、随机、安慰剂对照临床试验比较了一侧半面的活性成分XEP™-716 Miniprotein™与另一侧半面的活性成分XEP™-716 Miniprotein™。在每天两次使用含有 2.5% 或 5% XEP™-716 Miniprotein™ 的化妆品乳霜配方 28 天和 56 天之前和之后,所有测量均在颧骨部位进行。通过 CLSM 测量两个参数:DEJ 长度和边缘乳头数量,研究真皮-表皮交界处(DEJ)扁平减少的情况,从而证明其嫩肤特性。通过测量胶原纤维周长(CLSM)、真皮密度和真皮厚度(超声波)来评估真皮年轻化情况。结果体外实验结果证实,XEP™-716 Miniprotein™ 能够刺激关键的细胞外大分子,即 I 型胶原蛋白、透明质酸和弹性蛋白,其刺激水平与 TGF beta 生长因子诱导的水平相当。临床数据显示,局部使用 XEP™-716 Miniprotein™ 28 天和 56 天后,DEJ 长度、边缘乳头数量和胶原纤维周长均有显著的统计学增长。在同一时间点,面部皮肤的 B 扫描图像显示,真皮密度和厚度在统计学上有显著增加。这些结果表明,DEJ变得更加起伏,与真皮的连接更加紧密,而乳头状真皮则更加致密,这两种特征都是年轻皮肤的典型特征。本文中介绍的体外和临床结果表明,XEP™-716 Miniprotein™ 是一种有效的成分,可使成熟皮肤的 DEJ 和真皮层恢复活力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Dermatology and Therapy
Dermatology and Therapy Medicine-Dermatology
CiteScore
6.00
自引率
8.80%
发文量
187
审稿时长
6 weeks
期刊介绍: Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信