{"title":"Subcutaneous injection of genetically engineered exosomes for androgenic alopecia treatment.","authors":"Yukun Liu, Yonghong Liu, Jing Zhao, Tianyi Deng, Yinyin Ben, Ruitao Lu, Xusha Zhou, Runbin Yan, Xiaoqing Chen, Jian V Zhang, Grace Zhou","doi":"10.3389/fbioe.2025.1614090","DOIUrl":null,"url":null,"abstract":"<p><p>Androgenetic alopecia (AGA) is a common disorder that negatively impacts quality of life but remains challenging to treat effectively. The hair loss observed in AGA is the consequence of a gradual reduction in the duration of the anagen phase concomitant of the miniaturization of the hair follicles and subsequent atrophy. This process of miniaturization is associated with abnormalities in the Dihydrotestosterone (DHT) induced dermal papilla cells (DPCs). DHT induces DPCs senescence and promotes apoptosis of vascular endothelial cells and keratinocytes via the DPCs paracrine pathway, which ultimately leads to follicular miniaturization. In this study, we developed a multifunctional exosome-based targeted delivery platform, designated as EX104, through the engineering of HEK-293 cells to express a combination of therapeutical molecules, including WNT10B, VEGFA, and FGF7. EX104 reversed the hair follicle miniaturization phenotype in DHT-induced DPCs. Furthermore, it demonstrated significant hair growth-promoting effects in the murine model of androgenetic alopecia by remodeling the follicular microenvironment and restoring miniaturized hair follicles. Topical EX104 application demonstrated comparable hair growth promotion to first-line minoxidil, while significantly outperforming it in stimulating capillary growth and follicular proliferation. EX104 represents a promising and innovative strategy for AGA management and follicular regenerative therapy.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1614090"},"PeriodicalIF":4.3000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163060/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2025.1614090","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Androgenetic alopecia (AGA) is a common disorder that negatively impacts quality of life but remains challenging to treat effectively. The hair loss observed in AGA is the consequence of a gradual reduction in the duration of the anagen phase concomitant of the miniaturization of the hair follicles and subsequent atrophy. This process of miniaturization is associated with abnormalities in the Dihydrotestosterone (DHT) induced dermal papilla cells (DPCs). DHT induces DPCs senescence and promotes apoptosis of vascular endothelial cells and keratinocytes via the DPCs paracrine pathway, which ultimately leads to follicular miniaturization. In this study, we developed a multifunctional exosome-based targeted delivery platform, designated as EX104, through the engineering of HEK-293 cells to express a combination of therapeutical molecules, including WNT10B, VEGFA, and FGF7. EX104 reversed the hair follicle miniaturization phenotype in DHT-induced DPCs. Furthermore, it demonstrated significant hair growth-promoting effects in the murine model of androgenetic alopecia by remodeling the follicular microenvironment and restoring miniaturized hair follicles. Topical EX104 application demonstrated comparable hair growth promotion to first-line minoxidil, while significantly outperforming it in stimulating capillary growth and follicular proliferation. EX104 represents a promising and innovative strategy for AGA management and follicular regenerative therapy.
期刊介绍：
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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