ABSTRACT
Cell-based therapies have been used as promising treatments for several untreatable diseases. However, cellbased therapies have side effects such as tumorigenesis and immune responses. To overcome these side effects, therapeutic effects of exosomes have been researched as replacements for cell-based therapies. In addition, exosomes reduced the risk that can be induced by cell-based therapies. Exosomes contain biomolecules such as proteins, lipids, and nucleic acids that play an essential role in cell–cell and cell–matrix interactions during biological processes. Since the introduction of exosomes, those have been proven perpetually as one of the most effective and therapeutic methods for incurable diseases. Much research has been conducted to enhance the properties of exosomes, including immune regulation, tissue repair, and regeneration. However, yield rate of exosomes is the critical obstacle that should be overcome for practical cell-free therapy. Three-dimensional (3D) culture methods are introduced as a breakthrough to get higher production yields of exosomes. For example, hanging drop and microwell were well known 3D culture methods and easy to use without invasiveness. However, these methods have limitation in mass production of exosomes. Therefore, a scaffold, spinner flask, and fiber bioreactor were introduced for mass production of exosomes isolated from various cell types. Furthermore, exosomes treatments derived from 3D cultured cells showed enhanced cell proliferation, angiogenesis, and immunosuppressive properties. This review provides therapeutic applications of exosomes using 3D culture methods.
ABSTRACT
BACKGROUND@#Enhancing blood flow and cell proliferation in the hair dermis is critical for treating hair loss. This study was designed to aid the development of alternative and effective solutions to overcome alopecia. Specifically, we examined the effects of Morus alba.L root extract (MARE, which has been used in traditional medicine as a stimulant for hair proliferation) on dermal fibroblasts and other cell types found in the epidermis. @*METHODS@#We first optimized the concentration of MARE that could be used to treat human dermal fibroblasts (HDFs) without causing cytotoxicity. After optimization, we focused on the effect of MARE on HDFs since these cells secrete paracrine factors related to cell proliferation and angiogenesis that affect hair growth. Conditioned medium (CM) derived from MARE-treated HDFs (MARE HDF-CM) was used to treat human umbilical vein endothelial cells (HUVECs) and hair follicle dermal papilla cells (HFDPCs). @*RESULTS@#Concentrations of MARE up to 20 wt% increased the expression of proliferative and anti-apoptotic genes in HDFs. MARE HDF-CM significantly improved the tubular structure formation and migration capacity of HUVECs. Additionally, MARE HDF-CM treatment upregulated the expression of hair growth-related genes in HFDPCs. CM collected from MARE-treated HDFs promoted the proliferation of HFDPCs and the secretion of angiogenic paracrine factors from these cells. @*CONCLUSION@#Since it can stimulate the secretion of pro-proliferative and pro-angiogenic paracrine factors from HDFs, MARE has therapeutic potential as a hair loss preventative.