As wound healing is an extremely complicated process, consisting of a cascade of interlocking biological events, successful wound healing requires a multifaceted approach to support appropriate and rapid transitions from the inflammatory to proliferative and remodeling phases. In this regard, here the potential use of bovine milk extracellular vesicles (EVs) to enhance wound healing is investigated. The results show that milk EVs promote fibroblast proliferation, migration, and endothelial tube formation. In particular, milk EVs derived from colostrum (Colos EVs) contain various anti‐inflammatory factors facilitating the transition from inflammation to proliferation phase, as well as factors for tissue remodeling and angiogenesis. In an excisional wound mouse model, Colos EVs promote re‐epithelialization, activate angiogenesis, and enhance extracellular matrix maturation. Interestingly, Colos EVs are further found to be quite resistant to freeze‐drying procedures, maintaining their original characteristics and efficacy for wound repair after lyophilization. These findings on the superior stability and excellent activity of milk Colos EVs indicate that they hold great promise to be developed as anti‐inflammatory therapeutics, especially for the treatment of cutaneous wounds.
Human hair dermal papillary (DP) cells comprising mesenchymal stem cells in hair follicles contribute critically to hair growth and cycle regulation. The transition of hair follicles from telogen to anagen phase is the key to regulating hair growth, which relies heavily on the activation of DP cells. In this paper, we suggested exosomes derived from bovine colostrum (milk exosomes, Milk-exo) as a new effective non-surgical therapy for hair loss. Results showed that Milk-exo promoted the proliferation of hair DP cells and rescued dihydrotestosterone (DHT, androgen hormones)-induced arrest of follicle development. Milk-exo also induced dorsal hair re-growth in mice at the level comparable to minoxidil treatment, without associated adverse effects such as skin rashes. Our data demonstrated that Milk-exo accelerated the hair cycle transition from telogen to anagen phase by activating the Wnt/β-catenin pathway. Interestingly, Milk-exo has been found to stably retain its original properties and efficacy for hair regeneration after freeze-drying and resuspension, which is considered critical to use it as a raw material applied in different types of alopecia medicines and treatments. Overall, this study highlights a great potential of an exosome from colostrum as a therapeutic modality for hair loss.
In this study, we examined the potentially beneficial effects of bovine colostrum-derived exosomes on UV-induced aging and damage in three major resident skin cells including keratinocytes, melanocytes, and fibroblasts. The treatment with colostrum exosomes prevented the UV-induced generation of intracellular reactive oxygen species in epidermal keratinocytes. In UV-stimulated melanocytes, colostrum exosomes could also significantly reduce the production of the protective skin-darkening pigment melanin, which may help to reduce the risk of excessive melanin formation causing skin hyperpigmentation disorders. In the human dermal fibroblasts treated with colostrum exosomes, the expression of matrix metalloproteinases was suppressed, whereas increased cell proliferation was accompanied by enhanced production of collagen, a major extracellular matrix component of skin. Taken together, our findings indicate that bovine colostrum-derived exosomes having excellent structural and functional stability offer great potential as natural therapeutic agents to repair UV-irradiated skin aging and damage.
Extracellular vesicles (EV) deliver cargoes such as nucleic acids, proteins, and lipids between cells and serve as an intercellular communicator. As it is revealed that most of the functions associated to EVs are closely related to the immune response, the important role of EVs in inflammatory diseases is emerging. EVs can be functionalized through EV surface engineering and endow targeting moiety that allows for the target specificity for therapeutic applications in inflammatory diseases. Moreover, engineered EVs are considered as promising nanoparticles to develop personalized therapeutic carriers. In this review, we highlight the role of EVs in various inflammatory diseases, the application of EV as anti-inflammatory therapeutics, and the current state of the art in EV engineering techniques.
MicroRNAs
(miRNAs), a recently discovered class of noncoding RNAs,
play pivotal roles in regulating fundamental biological processes
by suppressing the expression of target genes. Aberrant miRNA expression
is commonly correlated with human diseases, including cancers. Anti-miRNA
oligonucleotides provide an innovative therapeutic strategy for silencing
disease-associated miRNAs. However, the clinical application of anti-miRNA
therapy has been limited by formulation challenges and physiological
delivery barriers. Here, to provide the safe and effective tumor-targeted
delivery of anti-miRNAs, we designed carrier-free maleimide-functionalized
anti-miRNAs (MI-Anti-miRNAs) that enable “piggybacking”
onto albumin in vivo. These functionalized MI-Anti-miRNAs
covalently bind to cysteine-34 of endogenous albumin within minutes.
In addition to resulting in a markedly extended blood circulation
lifetime, this strategy allows MI-Anti-miRNAs to “hitchhike”
to the tumor site. Importantly, in situ-generated
albumin-Anti-miRNAs are capable of intracellularly internalizing highly
negatively charged anti-miRNA molecules and knocking down target miRNAs.
In particular, MI-Anti-miRNAs that targeted miRNA-21, which is involved
in tumor initiation, progression, invasion, and metastasis in several
types of cancer, successfully repressed miRNA-21 activity, resulting
in a superior antitumor activity in both solid and metastatic tumor
models without causing systemic toxicity. This endogenous albumin-piggybacking
approach using MI-Anti-miRNAs provides a simple and broadly applicable
platform strategy for the systemic delivery of anti-miRNA therapeutics.
Extracellular vesicles (EVs), naturally secreted by cells, act as mediators for communication between cells. They are transported to the recipient cells along with cargoes such as nucleic acids, proteins, and lipids that reflect the changes occurring within the parent cells. Thus, EVs have been recognized as potential theranostic agents for diagnosis, treatment, and prognosis. In particular, the evidence accumulated to date suggests an important role of EVs in the initiation and progression of skin aging and various skin diseases, including psoriasis, systemic lupus erythematosus, vitiligo, and chronic wounds. This review highlights recent research that investigates the role of EVs and their potential as biomarkers and therapeutic agents for skin diseases and aging.
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