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

Yizuo Cai; Zhuoxuan Jia; Yichen Zhang; Bijun Kang; Chingyu Chen; Wei Liu; Wei Li; Wenjie Zhang

doi:10.1186/s13287-023-03398-1

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

Stem Cell Res Ther. 2023 Aug 23;14(1):219. doi: 10.1186/s13287-023-03398-1.

Authors

Yizuo Cai^#¹, Zhuoxuan Jia^#¹, Yichen Zhang², Bijun Kang¹, Chingyu Chen¹, Wei Liu³, Wei Li⁴, Wenjie Zhang⁵

Affiliations

¹ Department 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 China, 639 ZhiZaoJu Road, Shanghai, 200011, China.
² Department of Biological and Environmental Engineering, Cornell University, Ithaca, USA.
³ Department 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 China, 639 ZhiZaoJu Road, Shanghai, 200011, China. liuwei_md@126.com.
⁴ Department 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 China, 639 ZhiZaoJu Road, Shanghai, 200011, China. liweiboshi@163.com.
⁵ Department 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 China, 639 ZhiZaoJu Road, Shanghai, 200011, China. wenjieboshi@aliyun.com.

^# Contributed equally.

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, CEFFE^Low, CEFFE^Middle, CEFFE^High). 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.

Keywords: Androgenetic alopecia; Cell-free therapy; Fat extract.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue*
Alopecia* / drug therapy
Animals
Apoptosis
Biological Assay
Cell Extracts
Male
Mice
Mice, Inbred C57BL

Substances

Cell Extracts