Use of Stem Cell Extracellular Vesicles as a “Holistic” Approach to CNS Repair

Abstract

Neurodegeneration is a hallmark of many diseases and disorders of the central nervous system (CNS). High levels of neuroinflammation are often associated with irreparable damage to CNS cells due to the dysregulation of signaling cascades that are unable to restore a homeostatic balance. Due to the inherent complexity of the CNS, development of CNS-related therapeutics has met limited success. While stem cell therapy has been evaluated in the context of CNS repair, the mechanisms responsible for their functional properties have not been clearly defined. In recent years, there has been growing interest in the use of stem cell extracellular vesicles (EVs) for the treatment of various CNS pathologies as these vesicles are believed to mediate many of the functional effects associated with their donor stem cells. The potency of stem cell EVs is believed to be largely driven by their biological cargo which includes various types of RNAs, proteins, and cytokines. In this review, we describe the characteristic properties of stem cell EVs and summarize their reported neuroprotective and immunomodulatory functions. A special emphasis is placed on the identification of specific biological cargo, including proteins and non-coding RNA molecules, that have been found to be associated with stem cell EVs. Collectively, this review highlights the potential of stem cell EVs as an alternative to traditional stem cell therapy for the repair of cellular damage associated with diverse CNS pathologies.

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

“…Here specifically, we were interested in examining the functional effects of stem cell EVs on HIV-1 infected neurospheres. Our rationale was based on the results from numerous studies which have highlighted the protective and reparative properties of stem cell EVs among various CNS pathologies, as reviewed elsewhere [42,46,47,132].…”

“…Therefore, there is a need for a "holistic" reparative approach to potentially control cellular damage and regulate inflammation. There is mounting evidence that EVs from different sources of stem cells, namely MSCs and iPSCs, possess broad reparative and regenerative properties across various pathologies, including those related to the CNS [42,43,44,45,46,47]. Whether or not these vesicles confer reparative effects in the context of infection remains relatively unexplored, especially with respect to the CNS.…”

Mesenchymal Stem Cells as a Cornerstone in a Galaxy of Intercellular Signals: Basis for a New Era of Medicine

“…It has been reported that between 30 and 80% of protein-coding genes are regulated by miRNA. This is primarily achieved through the complementary binding of miRNA to a target mRNA sequence, resulting in either mRNA degradation or translational repression [ 166 ]. Circular RNA (circRNA) are closed-loop structures representing a unique class, highly stable form of non-coding RNA present in EVs [ 167 ].…”

Native and Bioengineered Exosomes for Ischemic Stroke Therapy

“…Exosomes have recently been investigated in many studies as a suitable alternative for the shortcomings of traditional agents due to their biological compatibility and particularly small size ( Arrighetti et al, 2019 ) for brain targeting ( Lapchak et al, 2018 ; Qu et al, 2018 ). Experimental studies provide new insight that exosomes and their cargo play important roles in nerve regeneration, synaptic function, plasticity, immune response, and exosome-mediated intercellular communication, contributing to brain reconstruction ( Qing et al, 2018 ; Liu et al, 2019 ; Branscome et al, 2020 ). Exosomes’ BBB crossing ability opens new getaways to the CNS, targeting the treatment of various neurodegenerative disorders, such as stroke, Alzheimer’s disease, tumors, and autoimmune diseases ( Abbott et al, 2006 ; Andreone et al, 2015 ).…”