Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo

Naseri, Zahra; Oskuee, Reza Kazemi; Jaafari, Mahmoud Reza; Moghadam, Mehdi Forouzandeh

doi:10.2147/ijn.s182384

Cited by 209 publications

(132 citation statements)

References 45 publications

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“…MSC-EVs may act as biological delivery platforms able to shuttle therapeutic molecules, such as miRNAs. Further, MSC-EV cargo may be engineered by either exogenous load [4] or reprogramming of the secreting cells [5,6], making direct load comparison an imperative challenge. From this perspective, a reliable normalization approach to select stable EVs-related miRNA RGs is mandatory and, to date, only few methods have been validated.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, by avoiding the concerns of using live and replicating cells that may undergo mal-differentiation or mutation, the idea of EVs as therapeutics is being explored, since they can mimic several biological actions of MSCs [1] through embedded lipids, proteins, mRNAs and miRNAs [2,3], therefore acting as biological nanocarriers. Even more intriguing, MSC-EVs may be engineered by either exogenous load [4] or reprogramming of the secreting cells [5,6] to shuttle and deliver specific and therapeutic molecules, such as miRNAs or mRNAs, eventually driving the focused influence on target cells [7]. As an example, in the orthopedic field, which is one of the most actively studied areas in regenerative medicine, miRNA-enriched MSC-EVs were shown to promote cartilage regeneration [5,6] by modulating ECM production.…”

Section: Introductionmentioning

confidence: 99%

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miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

et al. 2020

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Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and ΔCt method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

et al. 2020

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“…These UC-MSC-exosomes reduced proliferation of human osteosarcoma 143B and mouse osteosarcoma K7M2 cells in vitro in a dose-dependent manner by inducing apoptosis. The tumor-homing of MSC-exosomes has been successfully adopted to deliver therapeutic miRNAs to reduce tumors in xenograft mice with patient-derived pancreatic cancer [45], and syngeneic breast tumors in mice [90]. Interestingly, beyond organotropism of tumor exosomes, generalized tropism of tumor exosomes toward neoplastic tissues from different types or species have also been reported [106].…”

Section: Tumor-homing Of Exosomesmentioning

confidence: 99%

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Yi¹,

Lee²,

Kim

et al. 2020

IJMS

146

131

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Exosomes are nano-sized membranous vesicles produced by nearly all types of cells. Since exosome-like vesicles are produced in an evolutionarily conserved manner for information and function transfer from the originating cells to recipient cells, an increasing number of studies have focused on their application as therapeutic agents, drug delivery vehicles, and diagnostic targets. Analysis of the in vivo distribution of exosomes is a prerequisite for the development of exosome-based therapeutics and drug delivery vehicles with accurate prediction of therapeutic dose and potential side effects. Various attempts to evaluate the biodistribution of exosomes obtained from different sources have been reported. In this review, we examined the current trends and the advantages and disadvantages of the methods used to determine the biodistribution of exosomes by molecular imaging. We also reviewed 29 publications to compare the methods employed to isolate, analyze, and label exosomes as well as to determine the biodistribution of labeled exosomes.

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“…These exosomal RNAs (miRNAs, modified miRNAs and shRNAs) are fully functional when incubated with recipient cells and lead to target gene knockdown [11]. For example, Naseri et al demonstrated that MSCs-derived exosomes could be used as viable nanocarriers to deliver drug molecules, such as locked nucleic acid (LNA) modified anti-miR-142-3p oligonucleotides to inhibit miR-142-3p expression levels in vitro and in vivo in breast cancer [34]. Using a quantitative RT-PCR approach, we demonstrated that mature lentivirus-encoded antagomiR-4450 were secreted by lentivirus-infected hPLMSCs through exosomes.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

Yuan

Wang

Liu

et al. 2020

Preprint

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Background Exosomes derived from mesenchymal stem cells (MSCs) have emerged as novel drug and gene delivery tools. Current study aimed to elucidate the potential therapeutic role of human placental MSC (hPLMSC)-derived exosomes carrying antagomiR-4450 (EXO-antagomiR-4450) in intervertebral disc degeneration (IDD) progression. Methods Initially, the differentially expressed miRNAs related to IDD were identified by microarray analysis which provided data predicting the interaction between miR-4450 and ZNF121 in IDD. Next, miR-4450 and ZNF121 were elevated or silenced to determine their effects on the damage of NPCs treated with TNF-α. The therapeutic effects of EXO-antagomiR-4450 on nucleus pulposus cells (NPCs) were verified both in vitro and in vivo, especially gait analysis and fluorescent molecular tomopraphy were used in live IDD mice. Results Our results revealed that miR-4450 was highly expressed, while ZNF121 was poorly expressed in IDD patients and NPCs treated with TNF-α. Furthermore, miR-4450 was identified to specifically target ZNF121. Additionally, the inhibition of miR-4450 exerted an alleviatory effect on the inflammation, apoptosis and damage of the NPCs by up-regulating ZNF121. Moreover, EXO-antagomiR-4450 retarded damage of NPCs in vitro, alleviated IDD damage and ameliorated gait abnormality in vivo. Conclusion hPLMSC-derived exosomes could be a feasible nanovehicle to deliver inhibitory oligonucleotides like antagomiR-4450 in IDD.

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Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo

Cited by 209 publications

References 45 publications

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

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