Loss of collagen in the extracellular matrix is one of the manifestations of aging in skin. There are any number of very marginal approaches intended to improve matters presently available in clinics and stores, very few of which in any way address the underlying causes, or in only very minor ways if they do. Delivery of signals generated by healthy skin cells is an approach that might be more effective, but again this doesn't address the underlying causes of skin aging - it is an attempt to override cellular reactions to the aged environment. In this vein, researchers here demonstrate the harvesting of exosomes, small membrane bound packages that carry signals between cells, from cell cultures, and their delivery to aged skin as a possible therapy.
Researchers have shown that exosomes harvested from human skin cells are more effective at repairing sun-damaged skin cells in mice than popular retinol or stem cell-based treatments currently in use. Additionally, the nanometer-sized exosomes can be delivered to the target cells via needle-free injections. Exosomes are tiny sacs (30 - 150 nanometers across) that are excreted and taken up by cells. They can transfer DNA, RNA, or proteins from cell to cell, affecting the function of the recipient cell. In the regenerative medicine field, exosomes are being tested as carriers of stem cell-based treatments for diseases ranging from heart disease to respiratory disorders.
To test whether exosomes could be effective for skin repair, researchers first grew and harvested exosomes from skin cells. They used commercially available human dermal fibroblast cells, expanding them in a suspension culture that allowed the cells to adhere to one another, forming spheroids. The spheroids then excreted exosomes into the media. "These 3D structures generate more procollagen - more potent exosomes - than you get with 2D cell expansion."
In a photoaged, nude mouse model, the researches tested the 3D spheroid-grown exosomes against three other treatments: retinoid cream; 2D-grown exosomes; and bone marrow derived mesenchymal stem cells (MSCs) exosomes, a popular stem cell-based anti-aging treatment currently in use. The team compared improvements in skin thickness and collagen production after treatment. They found that skin thickness in 3D exosome treated mice was 20% better than in the untreated and 5% better than in the MSC-treated mouse. Additionally, they found 30% more collagen production in skin treated with the 3D exosomes than in the MSC treated skin, which was the second most effective treatment.