Researchers from North Carolina State University have demonstrated that exosomes harvested from human skin cells can repair sun-damaged skin cells in mice. The therapy also appears to be more effective than retinol and stem cell treatment, and best of all, delivery of the therapy is needle-free.
What are exosomes?
Exosomes are essentially membrane-wrapped packages that contain proteins and other molecules, are produced and released by cells, and deliver messages to other cells. When nearby cells intercept these packages, they change their behavior based on the information contained in these packages. You might think of exosomes being almost like messages in bottles traveling in the bloodstream between cells.
Extracellular vesicles have attracted significant interest in the scientific community in recent years due to their role in extracellular signaling. It has been known for a long time that cells release exosomes into the extracellular environment during apoptosis (cell death). However, the fact that healthy cells also release vesicles into the extracellular environment has only been realized more recently, and researchers are now busy finding ways to use the beneficial exosomes to treat diseases.
The researchers of this new study wanted to see if exosomes might be used as an effective approach to skin repair. The first step was to take human skin cells and allow them to replicate in a special 3D media that allowed the cells to stick to each other to form a spheroid-shaped mass. These spheroids produce more potent exosomes than cells grown in traditional media, making the method ideal for mass production and harvesting of secreted exosomes.
Next, they took photoaged mice and compared the performance of their 3D exosomes with a control group, a cream containing retinol, exosomes harvested from cells grown in traditional media, and exosomes harvested from bone marrow-derived mesenchymal stem cells (MSCs).
The researchers examined changes in skin thickness and the production of collagen following treatment and discovered that the exosomes from their 3D media increased skin thickness by 20% compared to untreated control mice. Skin thickness was also 5% better than MSC exosome-treated mice. Collagen production was also increased by 30% in the mice given exosomes from the 3D media, which made the 3D-derived exosomes the second most-effective treatment in this respect.
Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated in vitro and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-α) and the upregulation of transforming growth factor beta (TGF-β). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.
These results show the potential of using exosomes harvested from cells in 3D culture, and there are some real advantages to using them. Firstly, there is no risk of immune system rejection, which normally happens when immune cells in our body encounter cells from another body; exosomes are not cells, so there is no need to patient-match them for treatment, as they are universal.
Secondly, therapy does not have to be invasive or use needles due to the incredibly small size of the exosomes, as they can easily penetrate the skin via pressure, which is ideal for people who are squeamish and whose legs turn to jelly at the sight of a needle, including yours truly.
Exosomes have clear potential in treating skin aging caused by the sun and other sources.