Exosomes have unlocked a new avenue for scientific research and therapeutic medicine. Their small size, stability, malleable surface, targeted delivery, and enhanced absorption have recently gained attention. Their potential in the diagnostic and drug delivery fields is being explored. Exosome therapy is also paving the way for customized therapy tailored for the patient. Researchers are also investigating the prospects of exosomes in regenerative medicine. Derived from stem cells, these exosomes possess regenerative capabilities similar to stem cells but without the issues faced with the stem cells. Exosome therapy has demonstrated tremendous growth in facial rejuvenation treatment. With a multifaceted approach, exosomes have shown remarkable outcomes in the treatment of anti-aging, hyperpigmentation, and wound healing.
Mechanism behind Aging
Aging can occur due to genetic and environmental factors, largely categorizing it as intrinsic and extrinsic aging. Intrinsic aging is a natural phenomenon programmed into the genetic structure of a person. Extrinsic aging results from exposure to pollution, UV rays, heat, etc., that initiates cellular processes contributing to the early aging. Together these factors induce physiological changes such as wrinkles, creasing, dry skin, sagging skin, reduced elasticity, and hyperpigmentation. Thus, the aging process significantly deteriorates the appearance of a person. Numerous research studies have delineated mechanisms behind this process.
Cellular senescence:
Age-related accumulation of chromosomal damage and telomere shortening induce cellular senescence and apoptosis, decreasing the turnover of skin cells. UV ray exposure increases the oxidative stress in these cells by inhibiting antioxidants and augmenting the occurrence of reactive oxygen species (ROS). These ROS damages DNA, proteins, and lipids, which deteriorate the cell membrane, leading to the dysfunction, senescence, or apoptosis of cells. The effect manifests in the form of age spots and wrinkles.
Degradation of Extracellular Matrix:
Fibroblasts in the dermis layer produce extracellular matrix (ECM). But these cells markedly decrease with the aging process, thereby reducing the ECM synthesis. Moreover, UV radiation on its own and through ROS upregulates matrix metalloproteinases that degrade ECM components, further degenerating collagen and elastin fibers of ECM. Also, the keratin fibers located in the epidermis layer stiffen with age and lose the capacity of movement of water across them. The reduced density of ECM components combined with their degradation adversely affects the firmness and elasticity of the skin.
Angiogenesis:
Along with programmed cellular damage, aging also reduces the thickness of the papillary layer of dermis manifested as sagging of the skin. The age-related impaired angiogenesis also decreases the vascular density in the skin, thus alleviating the blood supply required for cell growth and development. Lipid content of the skin also diminishes owing to the aging process. Moreover, amino acids of the protein also undergo change, interfering with their water-binding capacity. On the other hand, UV ray exposure induces chronic inflammation through inflammatory cells and cytokines that further enhance ROS production and upregulate matrix metalloproteinases.
Benefits of Exosome Therapy for Anti-Aging
Exosomes are extracellular vesicles secreted by cells to mediate cell-cell signaling in a paracrine manner. Originally thought to be a cellular waste, the heterogeneous nature of exosomes proved there is more to them. Their content and characteristics depend upon the cells they originated from and drove in-depth research that uncovered their therapeutic potential. Their extraction from stem cells has provided an acellular alternative to stem cells. Unlike conventional treatments, exosomes act on all the degenerative processes and induce natural regenerative healing of the tissue, giving them an upper hand in the field of facial rejuvenation and anti-aging therapy.
Effect on cellular damage:
Cells like keratinocytes and fibroblasts are present in the epidermis and dermis layers of skin, respectively. The epidermis forms the outer layer of the skin and fibroblasts synthesize the extracellular matrix, thus maintaining the structure and function of the skin. Several studies have proven enhanced proliferation and migration of keratinocytes with the application of exosomes derived from mesenchymal stem cells. A research study by Wei Chen et al. demonstrated that these exosomes can also mitigate senescence in dermal fibroblasts by inhibiting the expression of senescence-related proteins. Additionally, the exosomes also promoted fibroblast migration. By enhancing the proliferation of cells and reducing their senescence, exosomes can heal the adverse impact of the aging process.
Effect on ECM:
Extracellular matrix (ECM) is composed of laminin, collagen, dermatan sulfate, perlocan, elastin, etc. Collagen and elastin are a few of the key components that provide mechanical strength, support, stability, firmness, and elasticity to skin. The team of Kwang-Won Seo and Kyung-Sun Kang conducted a study demonstrating that exosomes extracted from the umbilical cord mesenchymal stem cells prevented skin from the oxidative stress and promoted wound healing. In addition, these exosomes significantly decreased matrix metalloproteinases, increased collagen synthesis, as well as reduced cell apoptosis and senescence. A randomized study by Luiz-Chalres-de-Sa and team showed production of new elastin fibers and dermis remodeling with exosome application. This decrease in metalloproteinases would decrease the ECM degradation, while the production of elastin and collagen would enhance ECM deposition, returning the firmness and elasticity to skin.
Angiogenesis and Hyperpigmentation:
Exosomes also have anti-inflammatory and angiogenic properties that confer anti-aging effects. Kim et al. proved that exosomes isolated from the umbilical cord mesenchymal stem cells inhibit the protein involved in melanogenesis, thus effectively reducing melanin content and the resultant skin pigmentation. Exosomes also diminish ROS concentration, thus preventing further cellular damage.
Applications of Exosome Therapy
Cells secrete exosomes to mediate signaling; thus, exosomes contain all the necessary biomolecules that can induce the relevant response in specific cells. The stem cell-derived exosomes also contain such active molecules that act on specific cells and induce repair and regeneration of the tissue. The absence of the cellular component and their immunogenic potential, along with targeting specificity, makes exosomes excellent candidates as cost-effective and safe therapeutics. It has driven the scientists to explore the application of exosomes in other disorders as well.
Skin diseases:
In addition to aging, exosomes have been beneficial to other skin-related problems such as diabetic wounds, pressure ulcers, scleroderma, etc. The ability of exosomes to promote wound healing, cell proliferation, and ECM deposition has provided relief in these disorders. Moreover, exosomes have also shown inhibition of endothelial senescence along with increased angiogenesis. Combined together, these effects improve the blood supply to the affected tissue.
Scar Removal:
Exosomes derived from umbilical cord MSCs accelerate the scar healing process and reduce the width of scars by inhibiting the conversion of fibroblasts into myofibroblasts, inducing fibroblast proliferation, increasing collagen deposition, enhancing angiogenesis, and promoting re-epithelialization.
Hyperpigmentation:
Melanocytes in skin produce melanin to form a protective shield against harmful UV radiation. But the hyperactivated melanocytes produce excess melanin, leading to hyperpigmentation in the form of dark patches on the face. Administration of stem cell-derived exosomes significantly diminishes the levels of melanin by reducing the enzyme tyrosinase involved in melanin production.
Vitiligo:
Vitiligo is an autoimmune disorder in which the immune system destroys the melanin-producing cells, creating white patches on the skin. Umbilical cord blood MSCs-based exosomes regulate the immune system by inhibiting the immune cells that attack the cells and expanding regulatory immune cells that prevent the attack. These exosomes also lower the oxidative stress, thus decreasing the apoptosis of melanin-producing cells. Together, the exosomes act on the immune system and cell apoptosis to effectively reduce vitiligo.
Conclusion
The potential of stem cell-derived exosomes spans across multiple therapeutic areas. Stem cell-derived exosomes, in particular mesenchymal stem cells, have granted treatment benefits. The exosome therapy has lower toxicity in comparison to cellular therapies. Their regenerative abilities have been employed in the cosmetic field with successful outcomes. Here at Advancexo we provide high-quality exosomes derived from umbilical cord mesenchymal stem cells by following GMP-compliant methods and perform rigorous testing and characterization.
FAQs
Exosomes are vesicles that bud off from cells and are encapsulated by the lipid bilayer. They are nanometers in size and contain bioactive molecules like nucleic acids, proteins, lipids, etc. Cells secrete them to signal the neighboring cells and induce a specific response.
Anti-aging therapy requires tissue regeneration, which can be provided by stem cells. To
avoid the immune rejection risk associated with stem cells, exosomes are employed. Exosomes display a multitude of effects that mitigate the aging effects and restore the skin.
Exosomes have been isolated from various stem cells. But exosomes extracted from MSCs belonging to umbilical cord, also known as Wharton’s jelly, have demonstrated profound therapeutic effects. They are readily available. Advancexo, the exclusive manufacturer of exosomes in India, delivers exosomes packaged with anti-inflammatory and anti-aging miRNAs.