Mesenchymal stem cells as natural biofactories for exosomes carrying miR-124a in the treatment of gliomas

Lang, Frederick; Hossain, Anwar; Gumin, Joy; Momin, Eric N.; Shimizu, Yuzaburo; Ledbetter, Dan; Shahar, Tal; Yamashita, Shinji; Kerrigan, Brittany Parker; Fueyo, Juan; Sawaya, Raymond

doi:10.1093/neuonc/nox152

Cited by 193 publications

(149 citation statements)

References 36 publications

(48 reference statements)

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“…From then on, MEVs have been increasingly considered as substitutes for MSCs in drug delivery. Efforts have been made to improve the efficacy of MEV-based drug delivery for clinical use (Cheng et al, 2018b;Lang et al, 2018;Sharif et al, 2018;Jo et al, 2019;Li et al, 2019a;Perets et al, 2019;Riazifar et al, 2019). For example, a good manufacturing practice (GMP) standard for large-scale clinical MEVs production based on bioreactor has been established (Mendt et al, 2018).…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs' characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS. ARTICLE HISTORY

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Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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“…Exosomes can be enriched from peripheral blood samples and can be used to detect various proteins, lipids, and nucleic acids [17]. Exosomes have been used as drug delivery vehicles for the treatment of several CNS diseases [11,[18][19][20][21]. Exosomes are currently under investigation as therapeutic options for stroke [22].…”

Section: Introductionmentioning

confidence: 99%

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Lai

Liang

et al. 2020

J Neuroinflammation

133

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Background: Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation. Methods: Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels. Results: NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH. Conclusions: Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.

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“…This suggests the idea of taking exosomes for drug delivery. Several studies have reported that exosomes can be engineered as delivery vehicles by transferring functional biomolecules to cancer cells . Kamerkar et al .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that sFlt‐1 possesses anti‐tumor effects by inhibiting angiogenesis in many cancers . In addition, several studies have found that exosomes can be engineered as delivery vehicles for transferring functional biomolecules such as proteins, lipids, and nucleic acids (DNA, mRNA, and miRNA) to target cells …”

Section: Introductionmentioning

confidence: 99%

Soluble fms‐like tyrosine kinase‐1‐enriched exosomes suppress the growth of small cell lung cancer by inhibiting endothelial cell migration

Hao

Zhao

et al. 2019

Thoracic Cancer

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Background Previous studies have reported that soluble fms‐like tyrosine kinase‐1 (sFlt‐1) possesses anti‐tumor effects by inhibiting angiogenesis in many cancers. Exosomes can be engineered as delivery vehicles for transferring functional biomolecules, such as proteins, lipids, and nucleic acids (DNA, mRNA, and miRNA) to target cells to affect inflammation, apoptosis, and angiogenesis. The purpose of this study was to investigate whether exosomes can function as efficient carriers of sFlt‐1 in vitro and in vivo, to play a role in SCLC therapy. Methods We adopted three different methods: TEM, NTA and western blot analysis to characterize the cell‐derived exosomes from NCI‐H69 SCLC cell line and normal bronchial epithelial BEAS‐2B cell line. we next explored the effects of these exosomes on HUVE cell proliferation and migration in vitro.To verify sFlt‐1‐loaded exosomes suppress the tumor growth in vivo,we established subcutaneous xenografts in nude mice using the NCI‐H69 cell line. Results We observed that NCI‐H69‐exo significantly increased human umbilical vein endothelial cells (HUVEC) migration compared to BEAS‐2B‐exo in vitro and in vivo. sFlt‐1 protein expression was statistically higher in BEAS‐2B‐exo than NCI‐H69‐exo. sFlt‐1 protein or sFlt‐1‐enriched exosomes can inhibit the migration of HUVECs. Furthermore, sFlt‐1‐enriched exosomes exhibited higher inhibition efficacy on pro‐angiogenesis of NCI‐H69‐exo in comparison with the same concentration of sFlt‐1 protein. Intriguingly, sFlt‐1‐loaded exosomes showed marked anti‐tumor activity by inhibiting the growth of NCI‐H69 tumor xenografts. CD31 staining revealed that sFlt‐1‐loaded exosomes significantly reduced the vascular density of experimental mice. sFlt‐1‐loaded exosomes markedly induced tumor apoptosis and inhibited tumor cell proliferation in mice. Conclusion Exosomes from a SCLC cell line contain low levels of sFlt‐1 and significantly increased the migration of HUVECs. SFlt‐1‐enriched exosomes can inhibit NCI‐H69‐exo‐induced HUVEC migration. Exosomes enriched in sFlt‐1 have the potential to be effective therapeutic agents for SCLC.

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Mesenchymal stem cells as natural biofactories for exosomes carrying miR-124a in the treatment of gliomas

Abstract: MSCs can be used as natural biofactories to produce Exo-miR124, which is an effective antiglioma agent worthy of further clinical evaluation.

Cited by 193 publications

References 36 publications

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Soluble fms‐like tyrosine kinase‐1‐enriched exosomes suppress the growth of small cell lung cancer by inhibiting endothelial cell migration

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