Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia

Abstract Background Androgenetic alopecia (AGA) is one of the most common hair loss diseases worldwide. However, current treatments including medicine, surgery, and stem cells are limited for various reasons. Cell-free fat extract (CEFFE), contains various cell factors, may have potential abilities...

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Main Authors: Yizuo Cai, Zhuoxuan Jia, Yichen Zhang, Bijun Kang, Chingyu Chen, Wei Liu, Wei Li, Wenjie Zhang
Format: Article
Language:English
Published: BMC 2023-08-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-023-03398-1
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author Yizuo Cai
Zhuoxuan Jia
Yichen Zhang
Bijun Kang
Chingyu Chen
Wei Liu
Wei Li
Wenjie Zhang
author_facet Yizuo Cai
Zhuoxuan Jia
Yichen Zhang
Bijun Kang
Chingyu Chen
Wei Liu
Wei Li
Wenjie Zhang
author_sort Yizuo Cai
collection DOAJ
description Abstract Background Androgenetic alopecia (AGA) is one of the most common hair loss diseases worldwide. However, current treatments including medicine, surgery, and stem cells are limited for various reasons. Cell-free fat extract (CEFFE), contains various cell factors, may have potential abilities in treating AGA. This study aims to evaluate the safety, effectiveness and the underlying mechanism of CEFFE in treating AGA. Methods Sex hormone evaluation, immunogenicity assay and genotoxicity assay were conducted for CEFFE. In vivo study, male C57BL/6 mice were injected subcutaneously with dihydrotestosterone (DHT) and were treated with different concentration of CEFFE for 18 days (five groups and n = 12 in each group: Control, Model, CEFFELow, CEFFEMiddle, CEFFEHigh). Anagen entry rate and hair coverage percentage were analyzed through continuously taken gross photographs. The angiogenesis and proliferation of hair follicle cells were evaluated by hematoxylin–eosin, anti-CD31, and anti-Ki67 staining. In vitro study, dermal papilla cells (DPCs) were incubated with different concentrations of CEFFE, DHT, or CEFFE + DHT, followed by CCK-8 assay and flow cytometry to evaluate cell proliferation cycle and apoptosis. The intracellular DHT level were assessed by enzyme-linked immunosorbent assay. The expression of 5α-reductase type II, 3α-hydroxysteroid dehydrogenase and androgen receptor were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or/and western blot. Results In CEFFE-treated mice, an increase in the anagen entry rate and hair coverage percentage was observed. The number of CD31-positive capillaries and Ki67-positive cells were increased, suggesting that CEFFE promoted the proliferation of DPCs, modulated the cell cycle arrest, inhibited apoptosis caused by DHT, reduced the intracellular concentration of DHT in DPCs, and downregulated the expression of AR. Conclusions CEFFE is a novel and effective treatment option for AGA through producing an increased hair follicle density and hair growth rate. The proposed mechanisms are through the DHT/AR pathway regulation and regional angiogenesis ability.
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spelling doaj.art-a51f0f917b204a318441bd06441033b32023-11-19T12:33:46ZengBMCStem Cell Research & Therapy1757-65122023-08-0114111610.1186/s13287-023-03398-1Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopeciaYizuo Cai0Zhuoxuan Jia1Yichen Zhang2Bijun Kang3Chingyu Chen4Wei Liu5Wei Li6Wenjie Zhang7Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaDepartment of Biological and Environmental Engineering, Cornell UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of ChinaAbstract Background Androgenetic alopecia (AGA) is one of the most common hair loss diseases worldwide. However, current treatments including medicine, surgery, and stem cells are limited for various reasons. Cell-free fat extract (CEFFE), contains various cell factors, may have potential abilities in treating AGA. This study aims to evaluate the safety, effectiveness and the underlying mechanism of CEFFE in treating AGA. Methods Sex hormone evaluation, immunogenicity assay and genotoxicity assay were conducted for CEFFE. In vivo study, male C57BL/6 mice were injected subcutaneously with dihydrotestosterone (DHT) and were treated with different concentration of CEFFE for 18 days (five groups and n = 12 in each group: Control, Model, CEFFELow, CEFFEMiddle, CEFFEHigh). Anagen entry rate and hair coverage percentage were analyzed through continuously taken gross photographs. The angiogenesis and proliferation of hair follicle cells were evaluated by hematoxylin–eosin, anti-CD31, and anti-Ki67 staining. In vitro study, dermal papilla cells (DPCs) were incubated with different concentrations of CEFFE, DHT, or CEFFE + DHT, followed by CCK-8 assay and flow cytometry to evaluate cell proliferation cycle and apoptosis. The intracellular DHT level were assessed by enzyme-linked immunosorbent assay. The expression of 5α-reductase type II, 3α-hydroxysteroid dehydrogenase and androgen receptor were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or/and western blot. Results In CEFFE-treated mice, an increase in the anagen entry rate and hair coverage percentage was observed. The number of CD31-positive capillaries and Ki67-positive cells were increased, suggesting that CEFFE promoted the proliferation of DPCs, modulated the cell cycle arrest, inhibited apoptosis caused by DHT, reduced the intracellular concentration of DHT in DPCs, and downregulated the expression of AR. Conclusions CEFFE is a novel and effective treatment option for AGA through producing an increased hair follicle density and hair growth rate. The proposed mechanisms are through the DHT/AR pathway regulation and regional angiogenesis ability.https://doi.org/10.1186/s13287-023-03398-1Androgenetic alopeciaFat extractCell-free therapy
spellingShingle Yizuo Cai
Zhuoxuan Jia
Yichen Zhang
Bijun Kang
Chingyu Chen
Wei Liu
Wei Li
Wenjie Zhang
Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia
Stem Cell Research & Therapy
Androgenetic alopecia
Fat extract
Cell-free therapy
title Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia
title_full Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia
title_fullStr Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia
title_full_unstemmed Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia
title_short Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia
title_sort cell free fat extract restores hair loss a novel therapeutic strategy for androgenetic alopecia
topic Androgenetic alopecia
Fat extract
Cell-free therapy
url https://doi.org/10.1186/s13287-023-03398-1
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