The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells

Wolf, Tovah; Baier, Scott R.; Zempleni, Janos

doi:10.3945/jn.115.218586

Cited by 300 publications

(319 citation statements)

References 50 publications

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“…Although there are several reports on exosomes isolation from bovine milk using differential centrifugation alone [34, 35] or in combination with density gradient fractionation [13, 36] or precipitation [37, 38] methods, none of these describe quantitative yield of exosomes. When this manuscript was in preparation, Arntz et al , [39] reported differential centrifugation and filtration methods to isolate exosomes from commercial semi-skimmed milk and collected exosomes pellet at 110,000× g , with a reported yield of 200 mg protein per liter of milk.…”

Section: Discussionmentioning

confidence: 99%

Bovine milk-derived exosomes for drug delivery

et al. 2016

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Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. However, bulk, safe and cost-effective production of exosomes is not available. Here, we show that bovine milk can serve as a scalable source of exosomes that can act as a carrier for chemotherapeutic/chemopreventive agents. Drug-loaded exosomes showed significantly higher efficacy compared to free drug in cell culture studies and against lung tumor xenografts in vivo. Moreover, tumor targeting ligands such as folate increased cancer-cell targeting of the exosomes resulting in enhanced tumor reduction. Milk exosomes exhibited cross-species tolerance with no adverse immune and inflammatory response. Thus, we show the versatility of milk exosomes with respect to the cargo it can carry and ability to achieve tumor targetability. This is the first report to identify a biocompatible and cost-effective means of exosomes to enhance oral bioavailability, improve efficacy and safety of drugs.

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Section: Discussionmentioning

confidence: 99%

Bovine milk-derived exosomes for drug delivery

et al. 2016

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“…However, more studies are required to demonstrate that milk miRNAs, once ingested, can cross the GI tract of the infant [83,85]. Recent studies have shown the resistance of miRNA to degradation and that uptake of bovine milk exosomes by intestinal cells in vitro is mediated by temperature dependent-endocytosis [79,86]. A more recent study has provided evidence that porcine milk exosomal miRNAs modify gene expression and promote proliferation in intestinal cells in vitro and in vivo [87].…”

Section: Breast Milk Mirna: Possible Key Regulators and Noninvasivmentioning

confidence: 99%

Roles of MicroRNA across Prenatal and Postnatal Periods

Floris

Kraft

Altosaar

2016

IJMS

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Communication between mother and offspring in mammals starts at implantation via the maternal–placental–fetal axis, and continues postpartum via milk targeted to the intestinal mucosa. MicroRNAs (miRNAs), short, noncoding single-stranded RNAs, of about 22 nucleotides in length, are actively involved in many developmental and physiological processes. Here we highlight the role of miRNA in the dynamic signaling that guides infant development, starting from implantation of conceptus and persisting through the prenatal and postnatal periods. miRNAs in body fluids, particularly in amniotic fluid, umbilical cord blood, and breast milk may offer new opportunities to investigate physiological and/or pathological molecular mechanisms that portend to open novel research avenues for the identification of noninvasive biomarkers.

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“…Recent evidence suggesting that milk-derived miRNAs may have potential regulatory roles in modulating the immune system or metabolic processes of milk recipients still remain controversial [117][118][119][120][121][122][123][124]. Currently, there are two hypotheses about miRNA function in infants/offspring: the first proposes that milk miRNAs exert physiological regulatory functions after transferring to offspring, and the second assumes that miRNAs do not have any function but merely provide nutrition.…”

Section: Microrna Function In Milk Recipientsmentioning

confidence: 99%

Non-Coding RNA Roles in Ruminant Mammary Gland Development and Lactation

Ngoc¹,

Ibeagha‐Awemu²

2017

Current Topics in Lactation

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The ruminant mammary gland (MG) is an important organ charged with the production of milk for young and human nourishment. ) are a class of untranslated RNA molecules that function to regulate gene expression, associated biochemical pathways and cellular functions and are involved in many biological processes. This chapter presents a review of the current state of knowledge on the role of ncRNAs (particularly miRNAs and lncRNAs) in the MG and lactation processes, lactation signalling pathways, lipid metabolism, MG health of ruminants as well as miRNA roles in milk recipients. Finally, the potential application of new genome editing technology for ncRNA studies in MG development, the lactation process and milk components is presented.

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The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells

Abstract: The uptake of bovine milk exosomes is mediated by endocytosis and depends on cell and exosome surface glycoproteins in human and rat intestinal cells.

Cited by 300 publications

References 50 publications

Bovine milk-derived exosomes for drug delivery

Bovine milk-derived exosomes for drug delivery

Roles of MicroRNA across Prenatal and Postnatal Periods

Non-Coding RNA Roles in Ruminant Mammary Gland Development and Lactation

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