Comparative Analysis of Plant Exosomes and Human-Derived Exosomes: Structural Differences and Emerging Applications

Historical overview

Scientists began researching exosomes in the 1980s when they recognized that these vesicles assist reticulocytes in shedding their excess material to develop into blood cells. Research from the beginning decades misled professionals into believing exosomes were simple cellular waste.^[3] Research demonstrated they act as cells that communicate with each other directly. Scientific progress revealed immune regulatory roles for exosomes after Raposo and colleagues demonstrated their use as antigen-bearing vesicles in human cells.^[4] Scientists have conducted extensive research since their discovery to determine how human-derived exosomes can help fix damaged tissues while boosting immune response and healing wounds.

Plant scientists started studying plant-derived exosomes in the 2000s through work that showed these tiny vesicles assist plants in fighting pathogens.^[5] Under abiotic and biotic stress, P-EVs send out proteins and secondary metabolites that assist with plant defenses and are released as protective elements. Recent research highlights their medical value because H-EVs combine perfect compatibility with specific molecules that contain natural anti-inflammatory and antioxidant ingredients. Scientists now combine knowledge from different fields to best use plants and phages as EVs for medical and cosmetic products.^[6-8]

Purpose and scope of review

Our study aims to examine similarities and differences between how plants and humans generate exosomes and how these exosomes look. H-EVs demonstrate better therapeutic and cosmetic utilization than P-EVs, while both exosome types achieve promising results across cosmetic and medical applications. P-EVs have become more useful than other applications because they offer large-scale production at an affordable cost.

The study compares H-EVs with P-EVs by describing their different features, including markers on their surface membranes, embedded proteins, and lipid elements. The text explores how exosomes work independently to reduce inflammation and support tissue repair while communicating between cells and serving cosmetic purposes. The study compares EV types as a step toward developing treatment options that need manufacturing scale-up and oversight solutions. This review provides a foundational framework, highlighting promising directions for researchers to accelerate the development and rigorous testing of H-EVs, ultimately leading to next-generation cosmeceutical products. This narrative review aims to determine essential manufacturing and governance issues that affect the use of H-EVs in cosmeceutical products.

Biogenesis of H-EV

The human-derived exosome supply originates from the walls of the endosome that bend inward to form multivesicular bodies. H-EVs form through a natural process where lipids, proteins, and RNAs move inside intraluminal vesicles. MVBs send ILVs out of cells as exosomes through their natural membrane, merging with the outer plasma membrane. The steps that create H-EVs depend equally on the independent system and the dependent system of endosomal sorting complexes required for transport (ESCRT). The process requires Alix and tumor susceptibility gene (TSG101) proteins to help with both exosome membrane reshaping and loading materials.^[9]

Functional vesicles named H-EVs receive structural support from lipids like sphingomyelin and cholesterol, along with phospholipid phosphatidylserine. Membrane-bound tetraspanins CD9, CD81, and CD63 directly direct cellular cargo transport and targeting function. H-EVs can modify gene expression patterns in their target cells because they transport specific miRNA and lncRNA molecules. The Rab27 family of GTPases directs exosomes from MVBs to the plasma membrane for proper delivery to target organs.^[10]

Biogenesis of P-EV

After intracellular compartments produce them, P-EVs use membrane fusion to exit plants through the plasma membrane. P-EVs function best under stress conditions, including both pathogenic and non-pathogenic environmental triggers. Plant cellular processes that send vesicles to the cell surface depend on Rab GTPases and SNARE proteins alongside additional machinery, yet do not involve ESCRT systems found in human cells.^[11]

P-EV transport particles deliver stress protection molecules to plants, which include defense proteins, short RNAs, and secondary metabolite compounds. P-EVs deliver short RNA molecules that stop virulence genes of fungal diseases through interspecies communication, according to research.^[12] The addition of sterols and glycolipids to the EV lipid structure boosts P-EV stability and biological effects.

Comparative structural analysis

In spite of their basic lipid bilayer design, H-EVs and P-EVs feature substantial molecular dissimilarities regarding structure and action. H-EVs gain better cargo protection and membrane stability through the addition of phosphatidylserine, sphingomyelin, and cholesterol.^[8] EVs from plant sources display different lipid compositions with both sterol and glycolipid elements. The human (H)-EVs contain tetraspanins and HSPs, both specific to humans. Plant (P)-EVs contain plant glycoproteins and enzymes with uniqueness to plant cells. The content of RNAs in H-EVs differs from P-EVs: siRNAs and plant-specific regulatory RNA occupy P-EVs, while miRNAs and lncRNAs predominate in H-EVs in Table 1.

Anti-inflammatory and antioxidant roles: comparison of P-EVs and H-EVs

Regeneration therapy uses two distinct kinds of exosomes from plants or human sources to deliver anti-inflammatory and antioxidant benefits. H-EVs suppress inflammation by releasing microRNAs that control NF-κB pathway activation and reprogram immune cell behavior. These positive effects reduce both skin inflammation and stress levels, which benefit human health and lower disease risk.^[17]

P-EVs protect cells from oxidative damage by utilizing natural plant phytochemicals, particularly flavonoids and polyphenols. Research shows that ginger-derived exosomes lower inflammation and strengthen cells through their ability to counteract tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) pro-inflammatory substances.^[18] P-EVs work best in wide-scale, affordable settings because they scale well and blend easily with human bodies, yet H-EVs deliver custom methods for healing inflammation. These exosome types add value to medical and aesthetic treatments because they work well together.

P-EVs: Antioxidant and anti-inflammatory properties

P-EVs contain natural anti-inflammatory and antioxidant effects, which make them valuable for cosmetic use. Turmeric and grape plant-based exosomes contain flavonoids and polyphenols that fight reactive oxygen species (ROS) to protect your skin from oxidative stress. They promote damaged skin repair and skin rejuvenation through anti-inflammatory actions that block inflammatory signaling molecules. P-EVs bring benefits to cosmetic design because they offer sustainable production with natural ingredients. Exosomes help virus reproduction while protecting against viral infections. Exosomes serve as both main vehicles for viral spread and vital components of viral development. Respiratory viruses that appear in Figure 1 use exosome transmission pathways to start or govern inflammation actions. Exosomes serve as both a tool for transmitting viruses and controlling airway inflammation during their growth and decline.^[22]

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Figure 1:

Exosome-mediated regulation of the inflammatory pathway during respiratory viral disease RSV: Respiratory syncytial virus

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Treatment of cancer by H-EV

Research shows H-EVs from human cells display excellent properties to deliver cancer therapy because their transport reaches targeted cells without being detected by the immune system or causing harm to the body's normal cells. The targeted delivery of chemotherapeutic medicines through exosomes reduces treatment harm to the whole body while helping cancer cells. The exosomes demonstrated enhanced targeting accuracy for tumors while producing minimal damage to healthy tissues.^[23] EVs from human cells can deliver siRNA to both decrease tumor genes and enhance chemotherapy treatment. BRAS-targeted siRNAs used in exosomes stopped the growth of pancreatic tumors in research models during delivery.^[24] Research demonstrates that CRISPR-Cas9 systems carried out by exosomes successfully modify cancer genes and create new options for person-specific genomic treatment of tumors.^[25] Scientists are running tests [Table 2]^[26] to see if exosomes can fight cancer and when used as medicine or as testing tools to detect cancer earlier in its development.

Clinical potentials: H-EVs in neurodegenerative diseases, P-EVs in immune modulation

H-EVs have the ability to deliver neuroprotective treatments to the central nervous system through the blood-brain barrier, so they offer important possibilities for treating neurodegenerative conditions. Research shows that exosomes loaded with β-secretase siRNA can reduce amyloid-beta plaques that appear in Alzheimer's disease patients. Research shows H-EVs carrying neurotrophic factors, Glial cell line-derived Neurotrophic Factor (GDNF) and Brain-derived Neurotrophic Factor (BDNF), protect neurons and calm brain inflammation in Parkinson's disease models.^[27,28]

The naturally active ingredients in P-EVs make them outstanding immunomodulators. The microenvironment around tumors and the polarization of macrophages change when treated with exosomes sourced from ginger, which suppress tumor development.^[29] Details on how P-EVs control inflammation through siRNA and other regulatory molecules that block inflammatory processes have been proven effective in treating autoimmune diseases.^[30] Nanoparticles made from grape extracts preserve immune system health, while nanoparticles produced from ginger bring down colon cancer growth.^{[31, 32]} The combined benefits of P-EVs and H-EVs show they can benefit many different health problems [Table 3].

Production techniques: Challenges and improvements (H-EVs and P-EVs)

The production of exosomes faces different production problems with both human and plant-based sources, including issues with scale-up and chemical purity. The standard methods of ultracentrifugation and other EV separation turn out to be poor results and require much time to operate, making them unusable in mass production. These new processes using Tangential Flow Filtration (TFF) and Size Exclusion Chromatography (SEC) systems enhance exosome production at larger scales without any loss of functioning properties. The best strategy to achieve greater production yields is to grow exosome-producing cells inside bioreactor facilities.

Plant cells offer a good solution for P-EV manufacturing because they produce large collections at affordable costs. The process of separating exosomes gets less complex using filters and juice extraction. It remains difficult to maintain biological integrity and quality when manufacturing and storing plant-derived extracellular vesicles. Research teams use gradient ultrafiltration to develop better control over P-EV quality for medical use. New technologies need to be developed to meet growing demands for exosomes used in medical treatments and beauty products.^[33]

Safety profiles: H-EV vs. P-EV immunogenicity and biocompatibility

To make exosomes work in clinical practice, we must focus on their safety concerns. Although H-EVs show good compatibility with living tissues, they could trigger an immune response, particularly during allogeneic applications. High-purity procedures must filter both viruses and cell waste to make safe nucleic acids. Manufacturing autologous H-EVs from patient cells creates safety challenges despite their natural biosecurity.

Research shows P-EVs are nontoxic while also naturally suitable for human tissue and able to trigger an immune reaction. The manufacturing process from plants makes them ideal for cosmetic production because they meet safety and scalability requirements at scale. The safety of P-EV technology for human use depends on complete molecular evaluation and screening for plant-derived allergens. Safety systems for P-EVs and H-EVs require approval from authorities and courts to make people feel secure about using these products.

Production techniques

Exosome production for maximum output with high purity demands precise manufacturing methods. The common use of ultracentrifugation to separate H-EVs demands extensive labor with low production results. When aiming to scale up production while reducing expenses, companies prefer the newer methods of TFF and SEC technology more often.^[34] Simple extraction and filtration enable the straightforward removal of P-EVs from plant tissues for production at a commercial scale.

Expansion

Many technical challenges, alongside commercial, financial, and service problems, make it hard to produce human extracellular vesicles for medicine today. Due to their slow production and small-scale capabilities, today's ultracentrifugation and ultrafiltration isolation methods cannot work for industrial production.

Aspects: Regulatory and safety

Safe processes are needed to clean H-EV materials from dangerous particles, including infectious agents and other unwanted particles. Researchers need to develop better ways to control allogenic EVs' body response and make sure all EV products meet safety standards. Both PEVs and HEVs struggle to progress because regulators have not established standardized rules for these technologies. Research teams and regulatory authorities need to partner up to make PEV and HEV testing move more quickly into medical practice.^[35] Details of the production challenges and safety considerations for H-EVs and P-EVs are summarized in Table 4.

Challenges and future perspectives

Regulatory issues: Standardization hurdles for clinical applications

The structure for controlling clinical use of exosome-based therapies remains undeveloped due to several restrictions. The pandemic of exosome research faces major delays because scientists lack agreed-upon methods to separate, test, and verify these tiny structures. Scientists face complex tests when applying to make H-EVs because they worry about immune reactions, dirty supplies, and inconsistent production runs. Limited research supporting safe use in specific applications makes these problems harder to solve. Since P-EVs come from plants, they receive fewer regulatory rules, yet experts cannot decide if they should be labeled as medicine or standard health products. For exosome-based medicines to succeed clinically, researchers need to collaborate with producers and regulators.

Research gaps and innovations: Potential bioengineering solutions

Scientists need to solve several remaining challenges before exosome-based treatment can advance further. Our lack of full understanding about how exosomes form and receive their loads represents our biggest challenge in medical research. Advanced bioengineering can complete the knowledge gaps that help us design better exosome formations for medical therapy. Scientists adjust H-EVs to transport selected RNA or protein to boost their treatment benefits across both immune control and targeted dosing.

Research-based improvements to separation processes help P-EVs retain natural properties while achieving better production outputs. Bioengineering can enhance medicinal compound production within P-EVs through genetic plant modifications that enable better clinical application. By pairing H-EVs with P-EVs in coordinated therapy, patients may experience enhanced benefits to treat difficult medical and cosmetic problems. To bring exosome-based therapeutics to life, investment is needed in both cross-specialty studies and state-of-the-art manufacturing systems.