CosExo™ Exosome-NK(Exo-C03)

What Are Natural Killer (NK) Cell-Derived Exosomes?

Natural killer (NK) cell-derived exosomes are nano-sized extracellular vesicles, typically ranging from 40 to 160 nm in diameter, that carry a rich cargo of bioactive molecules reflective of their parent NK cells. These exosomes encapsulate a variety of functional proteins and regulatory factors, contributing to their unique biological activities. Key components of NK cell-derived exosomes include:

• Cytotoxic proteins: Perforin, granzyme A and B, Fas ligand (FasL), and tumor necrosis factor-alpha (TNF-α), which can directly induce apoptosis in target cells.
• Immune-regulatory molecules: Interferon-gamma (IFN-γ) and NKG2D receptors, important for activating and modulating immune responses.
• MicroRNAs (miRNAs): For example, miR-186, which regulates genes such as MYCN and TGFBR1, contributing to the inhibition of abnormal cell growth and immune evasion.

Advantages Compared to Stem Cell-Derived Exosomes

Natural killer (NK) cell-derived exosomes exhibit several distinctive advantages over stem cell-derived exosomes in specific applications:

• Targeted Cytotoxic Capability: NK exosomes carry cytotoxic proteins such as perforin and granzyme B, enabling them to selectively eliminate abnormal or damaged cells. In contrast, stem cell-derived exosomes primarily focus on promoting tissue repair and regeneration without direct cytotoxic activity.
• Deeper Immune Modulation: NK exosomes have the ability to directly regulate the activity of various immune cells, including T cells and macrophages, offering more effective control over chronic inflammatory processes. This broader immunomodulatory potential sets them apart from stem cell exosomes, which generally exert more limited immune regulatory effects.
• Enhanced Safety Profile: NK exosomes exhibit minimal impact on normal healthy cells, reducing the risk of unwanted side effects. In comparison, stem cell-derived exosomes, while beneficial for regeneration, carry a theoretical risk of promoting excessive cellular proliferation, which may contribute to fibrosis under certain conditions.

Verification of Exosome Isolation from NK-92MI Cells. (A) Transmission electron microscopy showing exosome morphology. (B) Western blot analysis confirming exosome markers (CD63, ALIX) and absence of negative markers (GM130, β-actin). (Zhu L, et al., 2017)

Potential Value of NK Cell-Derived Exosomes in Skin Health

• Promoting Skin Regeneration and Wound Healing

  Exosomes play a critical role in wound healing by promoting fibroblast proliferation, collagen synthesis, and angiogenesis, thereby accelerating tissue repair. While much research has focused on mesenchymal stem cell (MSC)-derived exosomes, exosomes from immune cells, including NK cells, are also believed to contribute to these processes. Studies suggest that exosomes can modulate cell behaviors involved in wound healing, enhance neovascularization, promote collagen deposition, and reduce inflammation, thus facilitating faster tissue regeneration. Although not all studies specifically examine NK cell-derived exosomes, the known involvement of immune cells in wound microenvironments and the role of exosomes as their effectors indicate a potential contribution of NK exosomes to skin regeneration and repair.

• Regulating Skin Inflammation

  Inflammation is a central feature of many skin conditions, including eczema, psoriasis, and aging-related skin deterioration. As key players in the immune system, NK cells release exosomes rich in immunomodulatory molecules that may influence inflammatory processes. Immune cell-derived exosomes have been shown to regulate various inflammatory pathways. NK exosomes can deliver specific microRNAs and proteins that modulate signaling cascades within target cells, either inhibiting the production of pro-inflammatory cytokines or promoting the release of anti-inflammatory mediators.

• Potential Anti-Aging Effects

  Skin aging is a multifactorial process involving reduced cellular function, diminished collagen and elastin production, and chronic low-grade inflammation. Exosomes, particularly those derived from stem cells, have gained attention for their ability to enhance cellular vitality, stimulate collagen synthesis, and mitigate oxidative stress. Although direct studies on the anti-aging effects of NK cell-derived exosomes are limited, their known capabilities in immune modulation and tissue repair suggest potential benefits. By improving the skin microenvironment, reducing inflammation, and supporting cellular health, NK exosomes may contribute to delaying visible signs of skin aging.

References

1. Wu C H, Li J, Li L, et al. Extracellular vesicles derived from natural killer cells use multiple cytotoxic proteins and killing mechanisms to target cancer cells. Journal of Extracellular Vesicles. 2019, 8(1): 1588538. https://doi.org/10.1080/20013078.2019.1588538
2. Zhu L, Kalimuthu S, Gangadaran P, et al. Exosomes derived from natural killer cells exert therapeutic effect in melanoma. Theranostics. 2017, 7(10): 2732. https://doi.org/10.7150/thno.18752
3. Lugini L, Cecchetti S, Huber V, et al. Immune surveillance properties of human NK cell-derived exosomes. The Journal of Immunology. 2012, 189(6): 2833-2842. https://doi.org/10.4049/jimmunol.1101988
4. Chelyapov N, Nguyen T T, Gonzalez R. Autologous NK cells propagated and activated ex vivo decrease senescence markers in human PBMCs. Biochemistry and Biophysics Reports. 2022, 32: 101380. https://doi.org/10.1016/j.bbrep.2022.101380

Case Study 1: NK Cell Exosomes Show Anti-Tumor Effects (Zhu L, 2017)

A study investigated NK-92 cell-derived exosomes (NK-92 Exo) for anti-tumor potential. Isolated NK-92 Exo contained cytotoxic proteins like perforin and FasL, plus TNF-α. In vitro, NK-92 Exo were cytotoxic to melanoma, gastric, and colon cancer cells, inducing apoptosis and inhibiting proliferation. They showed no significant toxicity to normal cells. In vivo, intratumoral injection of NK-92 Exo inhibited melanoma tumor growth in mice. These findings suggest NK cell-derived exosomes have promising anti-tumor activity and warrant further research as a potential immunotherapeutic strategy.

Figure 1. Cytotoxic Effects of NK Cell-Derived Exosomes on Melanoma Cells. B16F10/effluc melanoma cells were co-cultured with NK-92 Exo (5 and 20 µg). Bioluminescence imaging and CCK-8 assays showed a time- and dose-dependent decrease in cell viability at 10 h and 24 h. Data represent mean ± SD from triplicate experiments; *p < 0.05, ***p < 0.001.

Figure 2. NK-92 Exosome Effects on Normal Cell Proliferation. Phoenix-A cells were co-cultured with NK-92 Exo (5 and 20 µg). Bioluminescence imaging (A) and CCK-8 assay (B) showed no significant cytotoxicity even after 24 hours. Data are shown as mean ± SD from triplicate experiments.

References

1. Zhu L, Kalimuthu S, Gangadaran P, et al. Exosomes derived from natural killer cells exert therapeutic effect in melanoma. Theranostics. 2017, 7(10): 2732. https://doi.org/10.7150/thno.18752

• How are NK cell-derived exosomes being used in skin health or cosmetic products?

  NK cell-derived exosomes, like other exosomes, are being incorporated into cosmetic and skincare formulations such as lotions, face masks, and creams. The concept is that these exosomes can deliver their active cargo to target skin cells to promote beneficial effects.

• Can NK cell-derived exosomes be combined with other skincare ingredients?

  Yes, NK cell-derived exosomes can be integrated into formulations alongside other skincare ingredients. Their compatibility with various compounds allows for the development of multifunctional products. However, formulation stability and ingredient interactions should be carefully evaluated during product development.

• What is the recommended concentration of NK cell-derived exosomes in skincare formulations?

  The ideal concentration varies based on formulation goals and product type. Developers should rely on empirical data and performance targets to determine appropriate levels, ensuring both efficacy and safety, as standardized guidelines are still under investigation.

• Is CosExo™ Exosome-NK allowed for DIY formulation?

  No. it is for professional research or industrial manufacturing processes. Private use, including the self-formulation of cosmetics, food, or topical applications, is strictly forbidden. Creative Biostructure bears no responsibility for any adverse outcomes due to unauthorized handling.

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