Therapeutic Potential of Extracellular Vesicles for the Treatment of Nerve Disorders

Galieva, Luisa R.; James, Victoria; Mukhamedshina, Yana; Rizvanov, Albert A.

doi:10.3389/fnins.2019.00163

Cited by 74 publications

(49 citation statements)

References 70 publications

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“…In line with these findings, several studies demonstrated a beneficial impact on nerve regeneration after introducing ADSCs [26][27][28]. Of note, there is increasing evidence that the regenerative effect of stem cells is also mediated via extracellular vesicles (EVs) [29][30][31][32][33]. EVs are defined as heterogenous entities of phospholipid bilayer delimited vesicles without any means of replication that differ in their biogenesis, composition and size [34][35][36].…”

Section: Introductionmentioning

confidence: 83%

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Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Haertinger

Weiss

Mann

et al. 2020

Cells

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Recent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor binding, fusion to the SC membrane, or endocytosis mediated internalization. ADSCs, ADSC-EVs, and SCs were isolated from rats and characterized according to associated marker expression and properties. The proliferation rate of SCs in response to ADSC-EVs was determined using a multicolor immunofluorescence staining panel followed by automated image analysis. SCs treated with ADSC-EVs and silica beads were further investigated by 3-D high resolution confocal microscopy and live cell imaging. Our findings demonstrated that ADSC-EVs significantly enhanced the proliferation of SCs in a time- and dose-dependent manner. 3-D image analysis revealed a perinuclear location of ADSC-EVs and their accumulation in vesicular-like structures within the SC cytoplasm. Upon comparing intracellular localization patterns of silica beads and ADSC-EVs in SCs, we found striking resemblance in size and distribution. Live cell imaging visualized that the uptake of ADSC-EVs preferentially took place at the SC processes from which the EVs were transported towards the nucleus. This study provided first evidence for an endocytosis mediated internalization of ADSC-EVs by SCs and underlines the therapeutic potential of ADSC-EVs in future approaches for nerve regeneration.

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Section: Introductionmentioning

confidence: 83%

“…In addition, EVs may release their content into the extracellular space or act as antigen presenters [35,40]. Hence, ADSC derived EVs (ADSC-EVs) could offer a therapeutic alternative for regenerative approaches by avoiding the risk of cell-based therapies [29][30][31]43].…”

Section: Introductionmentioning

confidence: 99%

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Haertinger

Weiss

Mann

et al. 2020

Cells

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“…Experimental approaches for the treatment of SCI have been evolving and currently include a variety of approaches with a significant prevalence of genetic [43][44][45] and cellular therapies. Cells of adult organism, embryonic cells, and induced pluripotent stem cells have been used in multiple studies with variable effects [46][47][48], as has the application of extracellular vesicles as a cell-free therapy [49]. In the context of safety and practical capacity of translation into the clinic, MSCs appear to be the most promising therapy at the current time [50].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

et al. 2019

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Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

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“…This means that EVs have better advantages in the clinic in the treatment of nervous system diseases as compared to the therapeutic potential of MSCs. Moreover, MSC-EVs can avoid the risk of genetic changes associated with stem cell transplantation for the treatment of nerve disorders [264,265]. Remarkably, MSC-EVs can be modified to carry specific proteins or genes that promote cellular function and tissue repair.…”

Section: Extracellular Vesicles (Exosomes)mentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

340

274

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Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

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Therapeutic Potential of Extracellular Vesicles for the Treatment of Nerve Disorders

Cited by 74 publications

References 70 publications

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

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