Interspecies communication between plant and mouse gut host cells through edible plant derived exosome‐like nanoparticles

Abstract

Scope Exosomes, small vesicles participating in intercellular communication have been extensively studied recently; however, the role of edible plant derived exosomes in interspecies communication has not been investigated. Here, we investigate the biological effects of edible plant derived exosome-like nanoparticles (EPDEN) on mammalian cells. Methods and results In this study, exosome-like nanoparticles from four edible plants were isolated and characterized. We show that these EPDENs contain proteins, lipids and microRNA. EPDENs are taken up by intestinal macrophages and stem cells. The results generated from EPDEN transfected macrophages indicate that ginger EPDENs preferentially induce the expression of the anti-oxidation gene, heme oxygenase-1 (HO-1) and the anti-inflammatory cytokine, IL-10; whereas grapefruit, ginger, and carrot EPDENs promote activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Furthermore, analysis of the intestines of canonical Wnt reporter mice, i.e., B6.Cg-Tg(BAT-lacZ)3Picc/J mice, revealed that the numbers of β-galactosidase+ (β-Gal) intestinal crypts are increased, suggesting that EPDEN treatment of mice leads to Wnt mediated activation of the Tcf4 transcription machinery in the crypts. Conclusion The data suggest a role for EPDEN mediated interspecies communication by inducing expression of genes for anti-inflammation cytokines, anti-oxidation and activation of Wnt signaling, which are crucial for maintaining intestinal homeostasis.

RNA ‘Information Warfare’ in Pathogenic and Mutualistic Interactions

“…Furthermore, they have been implicated in delivering pollen allergens to humans [94]. Other remarkable evidence has come from biomedical studies and confirms exosome-like plant vesicles from somatic material as having the capacity to deliver bioactive molecules to other organisms [95,96]. Entirely supporting our thesis (illustrated in Figure 1 in main text), this class of vesicle from unrelated plant species was shown to contain RNAs, especially small RNAs [95].…”

Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites

“…Although this approach is promising, production of large quantities of mammalian cell nanoparticles and evaluation of their potential biohazards has been challenging. We have identified recently exosome-like nanoparticles from the tissue of edible plants including grapefruit, grapes, and tomatoes, and produced them in large quantities (15–17). As with mammalian exosomes, we have demonstrated that exosome-like nanoparticles from grapes naturally encapsulate small RNAs, proteins, and lipids.…”

Post Isolation Modification of Exosomes for Nanomedicine Applications

“…Large numbers of exosomes might then be isolated from culture or biological fluids using advanced microfluidic isolation strategies [39]. Other potential options to scale up exosomal nanocarrier production include the use of bovine milk-derived [40] or plant-derived [14,15] exosomes following biocompatibility testing.…”

“…Exosomes might be modified to serve as nanocarriers either endogenously at the cellular level or exogenously following cell culture production [1], collection from body fluids or even plant-based materials [14,15]. Endogenous exosome modification typically relies on molecular biology approaches to manipulate exosome components such as proteins at the source cell production level.…”