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Journal ArticleDOI

Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury

TLDR
The evidence that exosomes could be used as a neurorestorative therapy after stroke or traumatic brain injury is discussed and how engineering of their microRNA cargo could optimize this approach.
Abstract
Stroke is a leading cause of disability worldwide, and brain injuries devastate patients and their families, but currently no drugs on the market promote neurological recovery. Limited spontaneous recovery of function as a result of brain remodelling after stroke or injury does occur, and cell-based therapies have been used to promote these endogenous processes. Increasing evidence is demonstrating that the positive effects of such cell-based therapy are mediated by exosomes released from the administered cells and that the microRNA cargo in these exosomes is largely responsible for the therapeutic effects. This evidence raises the possibility that isolated exosomes could be used alone as a neurorestorative therapy and that these exosomes could be tailored to maximize clinical benefit. The potential of exosomes as a therapy for brain disorders is therefore being actively investigated. In this Review, we discuss the current knowledge of exosomes and advances in our knowledge of their effects on endogenous neurovascular remodelling events. We also consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy.

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Efficient Angiogenesis-Based Diabetic Wound Healing/Skin Reconstruction through Bioactive Antibacterial Adhesive Ultraviolet Shielding Nanodressing with Exosome Release.

TL;DR: An injectable adhesive thermosensitive multifunctional polysaccharide-based dressing with sustained pH-responsive exosomes release with great potential in achieving satisfactory healing in diabetic and other vascular-impaired related wounds was fabricated.
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Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury.

TL;DR: It is demonstrated that when given intranasally, exosomes derived from mesenchymal stem cells could pass the blood brain barrier, and migrate to the injured spinal cord area, and MSC-Exo loaded with phosphatase and tensin homolog small interfering RNA (ExoPTEN) could attenuate the expression of PTEN in thejured spinal cord region followingintranasal administrations.
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Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer.

TL;DR: This work demonstrated that BCa cell-secreted exosomes-mediated lymphangiogenesis promoted LN metastasis in BCa, which was in a VEGF-C-independent manner, and identified an exosomal long noncoding RNA (lncRNA), termed lymph node metastasis-associated transcript 2 (LNMAT2), which stimulated HLEC tube formation and migration in vitro and enhanced tumor lymphang iogenesis and LN tumours in vivo.
Journal ArticleDOI

Exosome engineering: Current progress in cargo loading and targeted delivery

TL;DR: The biogenesis, contents and functions of natural exosomes are summarized, and a comprehensive discussion for the strategies of exosomal cargo loading and membrane modification for targeted delivery is provided.
References
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Journal ArticleDOI

Shedding light on the cell biology of extracellular vesicles.

TL;DR: Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.
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Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes

TL;DR: It is shown that exosomes—endogenous nano-vesicles that transport RNAs and proteins—can deliver short interfering (si)RNA to the brain in mice, and the therapeutic potential of exosome-mediated siRNA delivery was demonstrated by the strong mRNA and protein knockdown of BACE1, a therapeutic target in Alzheimer's disease, in wild-type mice.
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Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes.

TL;DR: This work demonstrates the presence of exosomal and nonexosomal subpopulations within small EVs, and proposes their differential separation by immuno-isolation using either CD63, CD81, or CD9, and provides guidelines to define subtypes of EVs for future functional studies.
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Communication by Extracellular Vesicles: Where We Are and Where We Need to Go.

TL;DR: This Review focuses on the context of tumor cells and their microenvironment, but similar results and challenges apply to all patho/physiological systems in which EV-mediated communication is proposed to take place.
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Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats

TL;DR: MSCs delivered to ischemic brain tissue through an intravenous route provide therapeutic benefit after stroke and may provide a powerful autoplastic therapy for stroke.
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