Understanding The Basics Of Exosomes in Skin

Exosomes are extracellular vesicles that are produced by cells and carry proteins, lipids, and nucleic acids. They act as messengers between cells and play an important role in intercellular communication. In skin, exosomes have emerged as key players in processes like wound healing, aging, and more. This article will provide an overview of exosomes in skin biology and their potential applications.

What are Exosomes?

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Exosomes are small membranous vesicles, typically 30-150 nm in size, that originate within endosomes of most cell types. Endosomes are membrane-bound compartments within cells that function to move materials into and out of the cell. As endosomes mature, they accumulate intracellular cargo like proteins and RNAs. The endosomes then bud inward forming intraluminal vesicles (ILVs) that contain this molecular cargo. These ILV-containing endosomes are called multivesicular bodies (MVBs). When MVBs fuse with the plasma membrane, the ILVs are released extracellularly as exosomes.

Once released, exosomes can travel to nearby cells or to distant sites through biological fluids. Exosomes contain biomolecules from their cells of origin, so they serve as vehicles for intercellular communication and influence recipient cell function. Key molecules found in exosomes include proteins like tetraspanins and heat shock proteins, lipids like cholesterol and ceramide, and nucleic acids which can include mRNA, microRNA, long non-coding RNA, and mitochondrial DNA. The specific composition of exosomes depends on the origin cell type and physiological condition. Let us talk about exosomes in skin and more.

Exosome Biogenesis and Release

Exosome in skin biogenesis begins with endocytosis, the process by which cells internalize molecules from outside the cell by engulfing them with their cell membrane. This forms vesicle compartments called endosomes that mature through early to late endosomes and finally MVBs. During endosomal maturation, ubiquitinated proteins are sorted into ILVs by the ESCRT (endosomal sorting complex required for transport) machinery. Other mechanisms of ILV formation independent of ESCRT also exist. The mature MVBs can either fuse with lysosomes for degradation or fuse with the plasma membrane to release exosomes.

The release of exosomes in skin is a highly regulated process influenced by various cellular factors and extracellular stimuli. Components of the Rab GTPase family, particularly Rab27 and Rab35, are involved in MVB docking at the plasma membrane. Soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) like YKT6 mediate the fusion event releasing ILVs as exosomes. Extracellular triggers like hypoxia, cellular stress, EMT (epithelial to mesenchymal transition), and elevation of intracellular calcium can stimulate exosome release. Once discharged, exosomes interact with recipient cells by binding surface receptors, fusing with the target cell membrane, or being internalized by endocytosis.

Exosomes in Skin Function and Homeostasis

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The skin is the body’s largest organ and forms a first line of defense against the external environment. Exosomes secreted by skin cells have emerged as important mediators of normal skin function and homeostasis. Here are some of the key roles:

• Wound healing: Exosomes in skin from mesenchymal stem cells can promote cutaneous wound healing by enhancing proliferation and migration of skin cells like fibroblasts and keratinocytes. They also stimulate angiogenesis to aid wound closure.
• Immune modulation: Exosomes in skin from keratinocytes and melanocytes modulate immune responses in skin by transporting antigens and inflammatory mediators. They help maintain skin immune tolerance in homeostasis.
• Epidermal differentiation: Keratinocyte-derived exosomes influence differentiation and growth of other keratinocytes to form the stratified epidermis with a protective barrier function.
• Pigment transfer: Melanocyte exosomes in skin can transfer melanin pigment particles to surrounding keratinocytes which contributes to skin pigmentation and photoprotection.
• Hair follicle cycling: Exosomes secreted within the skin microenvironment contain factors that promote hair follicle growth and cycling between the anagen (growth) and catagen (regression) phases.
• Anti-aging: Exosomes from mesenchymal stem cells and other sources can counteract skin aging by reducing oxidative stress, stimulating collagen synthesis, and promoting hyaluronan production.

Given these important physiological roles, exosome signaling is necessary for skin health and disruption of normal exosome function may contribute to various skin disorders.

Exosomes in Cutaneous Diseases and Disorders

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As exosomes have diverse functions in skin, aberrations in exosome quantity or composition can lead to various cutaneous pathologies. Exosomes in skin may contribute to disease pathology through altered intercellular communication, propagation of harmful factors, or impaired skin repair. Some of the skin conditions linked to exosomes include:

• Psoriasis: Keratinocyte-derived exosomes promote inflammation in psoriasis by activating immune cells and expressing high levels of IL-17 and TNF-alpha. Exosomes isolated from psoriatic lesions can transmit the inflammatory condition to healthy skin.
• Atopic dermatitis: Exosomes isolated from the plasma and skin lesions of atopic dermatitis patients show altered miRNA and gene expression profiles. The composition of such exosomes may perpetuate inflammation and impair barrier function.
• Vitiligo: Exosomes in skin isolated from vitiligo patients have an inflammatory miRNA profile. Oxidative stress in vitiliginous keratinocytes also causes them to release exosomes that propagate melanocyte loss.
• Skin cancer: Tumor-derived exosomes can promote metastases and therapy resistance in melanoma. Exosomes in skin from squamous cell carcinoma advance tumor growth and immune suppression.
• Impaired wound healing: In diabetic patients, improper fibroblast exosome in skin release impedes re-epithelialization and collagen deposition in chronic skin wounds. Exosomes may also drive excessive inflammation and fibrosis in abnormal wound healing.
• Skin aging: An age-dependent decline in fibroblasts leads to reduced exosome secretion which impairs collagen production in aged skin. Also, senescent cell-derived exosomes accumulate and cause inflammation which further promotes skin aging.

Advances in exosome research will help elaborate molecular details on their contributions to such skin disorders. This can open new possibilities for diagnostic, prognostic, and therapeutic applications.

Exosomes as Biomarkers of Skin Health and Disease

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Exosomes isolated from skin and other tissues or biofluids provide valuable biomarkers for diverse cutaneous conditions. As exosomes in skin contain molecular cargo reflecting the physiological state of source cells, their contents can offer insights into disease pathology and progression. Some examples of utilizing exosomes as minimally invasive biomarkers in dermatology include:

• Gene mutations and expression changes characteristic of melanoma, squamous cell carcinoma, and other skin cancers can be detected in tumor-derived exosomes.
• The exosomal proteome and transcriptome is altered in psoriatic lesions and plasma exosomes, serving as signatures of disease activity.
• Exosomes from atopic dermatitis patients have distinct miRNA expression profiles that correlate with immune dysfunction and skin barrier impairment.
• Oxidative stress markers are elevated in plasma exosomes of vitiligo patients while miRNAs related to melanogenesis are decreased.
• Aggregation of amyloid beta and phosphorylated tau in exosomes in skin may serve as early biomarkers for cutaneous amyloidosis.
• Exosomal cargo differ significantly between acute and chronic wound fluid and can denote prolonged inflammation or stalled tissue remodeling.
• Senescent cell-derived exosomes accumulate in aged skin and reflect underlying inflammation that drives intrinsic skin aging.

Further research can expand the utility of exosomes as clinical biomarkers for diagnosis, disease subtyping, treatment selection, and monitoring therapeutic outcomes. Analyzing the molecular contents of exosomes using omics approaches provides a powerful platform for biomarker discovery.

Exosomes for Treatment of Skin Disorders

Beyond biomarkers, exosomes also hold promise as therapeutic agents or vehicles for skin diseases. Key approaches under exploration include:

• Mesenchymal stem cell-derived exosomes can accelerate cutaneous regeneration and reduce inflammatory responses in wounds and scars. They may be applied topically or injected at wound sites.
• Exosomes in skin engineered to overexpress antifibrotic or anti-inflammatory miRNAs can help resolve abnormal scarring or inflammatory dermatoses when applied as a nanotherapy.
• Tumor-targeted exosomes loaded with chemotherapeutic drugs or silencing RNAs can serve as nanocarriers for precision treatment of melanomas and other skin cancers.
• Topical application of antioxidant exosomes in skin may counteract oxidative damage and thereby slow down intrinsic skin aging.
• Exosomes derived from induced pluripotent stem cells could stimulate hair follicle regeneration to treat hair loss conditions like androgenic alopecia.
• Plant-derived exosomes loaded with active botanical compounds may protect and nourish skin when formulated into topical cosmeceuticals.

Despite therapeutic promise, most exosome-based strategies currently remain in preclinical stages of testing. More research is vital to evaluate safety, targeting efficiency, and clinical effectiveness of exosomes in skin for diverse dermatological applications.

Top 5 Skincare Products with Exosomes in skin

As research on exosomes grows, more skincare brands are harnessing exosome technology in anti-aging and restorative products. Here are 5 top-rated skincare products that feature exosomes:

1. Elizabeth Arden Prevage Anti-Aging Daily Serum

image credits: Elizabeth Arden

This lightweight serum contains melon fruit-derived exosomes that work to shield skin from environmental stressors and support collagen and elastin production for a firmer, smoother complexion.

2. Chantecaille Rose de Mai Cream

image credits: Chase Amie

Formulated with plant stem cell exosomes from the iconic Chantecaille rose, this moisturizer nourishes skin while strengthening the skin barrier, reducing signs of aging.

3. La Prairie Platinum Rare Haute-Rejuvenation Protocol

image credits: Forbes

A two-step rejuvenating skincare regimen powered by Swiss Alpine plant stem cell exosomes that target wrinkles, loss of firmness and deliver intense hydration.

4. Elemis Pro-Collagen Quartz Lift Serum

image credits: Lookfantastic India

Formulated with Padina Pavonica seaweed exosomes, this concentrated serum reduces wrinkles and fine lines, leaving a firmer, contoured facial profile.

5. Omorovicza Miracle Facial Oil

image credits: Omorovicza

• This luxurious anti-aging facial oil contains exosomes from apple stem cells and other oils that renew skin elasticity, radiance, and youthfulness. The exosome in skin blend also protects against environmental damage.

While still an emerging technology, exosome-enriched skincare shows promise in replenishing aging skin. More clinical studies are needed to substantiate their long-term benefits for skin health and beauty.

Conclusion

Exosomes in skin are now recognized as important mediators of skin cell communication with multifaceted roles in cutaneous homeostasis, aging, regeneration, and disease. Ongoing research on exosomal function and cargo continues to unravel their involvement in skin biology. Further exploration of their diagnostic, prognostic, and therapeutic potential may lead to exciting new advancements in dermatology. However, challenges like batch-to-batch variability, lack of standardized isolation.

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