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雄激素性脱发实验室模型的评估:一项系统综述。

An appraisal of laboratory models of androgenetic alopecia: A systematic review.

作者信息

Ntshingila S, Khumalo N P, Engel M, Arowolo A T

机构信息

Hair and Skin Research Laboratory Division of Dermatology Department of Medicine Faculty of Health Sciences and Groote Schuur Hospital University of Cape Town Cape Town South Africa.

Department of Medicine Faculty of Health Sciences and Groote Schuur Hospital University of Cape Town Cape Town South Africa.

出版信息

Skin Health Dis. 2021 Mar 5;1(2):e15. doi: 10.1002/ski2.15. eCollection 2021 Jun.

Abstract

BACKGROUND

Androgenetic alopecia (AGA) is the most common form of non-scarring alopecia in humans. Several studies have used different laboratory models to study the pathogenesis and interventions for AGA. These study models have proved beneficial and have led to the approval of two drugs. However, the need to build on existing knowledge remains by examining the relevance of study models to the disease.

OBJECTIVE

We sought to appraise laboratory or pre-clinical models of AGA.

METHOD

We searched through databases (PubMed, ScienceDirect, Web of Science, World CAT, Scopus and Google Scholar) for articles on AGA-related studies from 1942 to March 2019 with a focus on study models.

RESULTS

The search rendered 101 studies after screening and deduplication. Several studies (70) used in vitro models, mostly consisting of two-dimensional monolayer cells for experiments involving the characterization of androgen and 5-alpha reductase (5AR) and inhibition thereof, the effects of dihydrotestosterone (DHT) and biomarker(s) of AGA. Twenty-seven studies used in vivo models of mice and monkeys to investigate DHT synthesis, the expression and inhibition of 5AR and hair growth. Only four studies used AGA-related or healthy excisional/punch biopsy explants as ex vivo models to study the action of 5AR inhibitors and AGA-associated genes. No study used three-dimensional [3-D] organoids or organotypic human skin culture models.

CONCLUSION

We recommend clinically relevant laboratory models like human or patient-derived 3-D organoids or organotypic skin in AGA-related studies. These models are closer to human scalp tissue and minimize the use of laboratory animals and could ultimately facilitate novel therapeutics.

摘要

背景

雄激素性脱发(AGA)是人类非瘢痕性脱发最常见的形式。多项研究使用了不同的实验室模型来研究AGA的发病机制和干预措施。这些研究模型已被证明是有益的,并促成了两种药物的获批。然而,仍有必要通过检验研究模型与该疾病的相关性来拓展现有知识。

目的

我们试图评估AGA的实验室或临床前模型。

方法

我们在数据库(PubMed、ScienceDirect、Web of Science、World CAT、Scopus和谷歌学术)中搜索了1942年至2019年3月期间关于AGA相关研究的文章,重点关注研究模型。

结果

经过筛选和去重后,搜索得到101项研究。多项研究(70项)使用了体外模型,主要由二维单层细胞组成,用于涉及雄激素和5α还原酶(5AR)的表征及其抑制、二氢睾酮(DHT)的作用以及AGA生物标志物的实验。27项研究使用小鼠和猴子的体内模型来研究DHT合成、5AR的表达和抑制以及毛发生长。只有四项研究使用AGA相关或健康的切除/打孔活检外植体作为离体模型来研究5AR抑制剂和AGA相关基因的作用。没有研究使用三维[3-D]类器官或器官型人类皮肤培养模型。

结论

我们建议在AGA相关研究中使用与临床相关的实验室模型,如人源或患者来源的3-D类器官或器官型皮肤。这些模型更接近人类头皮组织,最大限度地减少了实验动物的使用,并最终可能促进新型治疗方法的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faa4/9060143/caa98a4bc9da/SKI2-1-e15-g001.jpg

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