Exosomes Secreted from Adipose-Derived Stem Cells Are a Potential Treatment Agent for Immune-Mediated Alopecia

Abstract

Background. Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth in vitro and in vivo for potentially treating immune-mediated alopecia and further exploring the underlying mechanism. Methods. Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established in vivo; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real‐time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq). Results. ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF-α signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/β-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice. Conclusion. ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/β-catenin signaling pathway, and the TNF-α signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.

Application of Cell-Derived Extracellular Vesicles and Engineered Nanovesicles for Hair Growth: From Mechanisms to Therapeutics

“…ADSC-Exos treated in vivo skin showed increased expression of Wnt3A, AXIN2, and SFRP1 mRNA. This study provides the potential for developing ADSC-Exos as promising therapeutic EVs for immune-mediated alopecia ( Li et al, 2022 ).…”

“…Another study showed that human neural progenitor cell - derived EVs containing miR-100-5p increased the levels of β-catenin, C-myc, and Cyclin D1 in DPCs and these effects were abolished when miR-the DPCs were treated with miR-100-5p inhibitors ( Cao et al, 2021 ). Finally, mouse ADSC-derived EVs were shown to carry low levels of miR-22-5p and miR-22-3p; use of inhibitors against miR-22 diminished the hair inductive ability ( Li et al, 2022 ). These results suggest that miR-100-5p, miR-22-5p, and miR-22-3p have a critical role in activating β-catenin-relayed signaling pathways.…”

“…In general, hair is a threadlike outgrowth of the outer layer of the skin (epidermis) and is a key feature of mammals, playing an important role in their appearance, social acceptance, and self-confidence ( Qi and Garza, 2014 ). Hair loss can be caused by many factors, including hormonal changes, nutritional deficiencies, genetics, medications, inflammation, injuries, and even surgeries ( Guo and Katta, 2017 ; Rajendran et al, 2017 ; Li et al, 2022 ). The hair follicle (HF) is a self-renewing mini-organ that undergoes a cycle of stages known as anagen, catagen, and telogen.…”

Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles

“…In recent years, EVs have emerged as potential therapeutic candidates for various diseases, including ischemic diseases, wound healing, and hair regrowth, by delivering their cargo to target cells[ 8 - 12 ]. EVs or nanovesicles from DP cells[ 13 - 17 ], fibroblasts[ 18 , 19 ], stem cells[ 11 , 20 ], macrophages[ 21 , 22 ] and neural progenitor cells[ 23 ] have been shown to have potential therapeutic effects on hair growth in recent studies. Nearly half of these studies have reported enhanced hair regrowth using DP cells as the source cells, which showed potential as therapeutic candidates for hair regrowth.…”

Stem cell secretome as a mechanism for restoring hair loss due to stress, particularly alopecia areata: narrative review

“…Furthermore, the Wnt/-catenin signaling pathway was activated in the skin of ADSC-Exosome-treated mice, according to qRT-PCR and western blotting data. ADSC-Exosome therapy improved hair regeneration via modifying miR-22, the Wnt/-catenin signaling system, and the TNF-signaling pathway, indicating that ADSC-Exosome may be a potential cell-free therapeutic strategy for immune-mediated alopecia [ 51 ].…”