Mesenchymal stromal cells as multifunctional cellular therapeutics – a potential role for extracellular vesicles

Stephen, Jillian; Bravo, Elena Lopez; Colligan, David; Fraser, Alasdair R.; Petrík, Juraj; Campbell, John

doi:10.1016/j.transci.2016.07.011

Cited by 31 publications

(24 citation statements)

References 65 publications

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“…EVs play a pivotal role in stem cell plasticity and tissue regeneration, possibly contributing to the paracrine action observed upon MSCs cell transplant [92, 93]. Purification of EVs released from cultured MSCs and their delivery to damaged tissues may represent a novel “acellular” therapeutic approach in the arena of regenerative medicine [14, 51].…”

Section: Mesenchymal Stem/stromal Cells-derived Extracellular Vesimentioning

confidence: 99%

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies forIn VivoTracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

116

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Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge about in vivo EVs trafficking upon delivery is required before effective clinical translation. Only a few studies have focused on the biodistribution analysis of exogenously administered MSCs-derived EVs. Nevertheless, current strategies for in vivo tracking in animal models have provided valuable insights on the biodistribution upon systemic delivery of EVs isolated from several cellular sources, indicating in liver, spleen, and lungs the preferential target organs. Different strategies for targeting EVs to specific tissues to enhance their therapeutic efficacy and reduce possible off-target effects have been investigated. Here, in the context of a possible clinical application of MSC-derived EVs for tissue regeneration, we review the existing strategies for in vivo tracking and targeting of EVs isolated from different cellular sources and the studies elucidating the biodistribution of exogenously administered EVs.

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Section: Mesenchymal Stem/stromal Cells-derived Extracellular Vesimentioning

confidence: 99%

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies forIn VivoTracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

116

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“…Therefore, the functional behavior of these EV and their effects on recipient cells are probably ‘donor’ cell/organism- and niche/context-specific ( Nolte-‘t Hoen and Wauben, 2012 ). The immunological imprinting by EV has been spearheaded by previous studies on EV derived from mammalian immune cells (reviewed in Thery et al, 2009 ; Nolte-‘t Hoen and Wauben, 2012 ; Robbins and Morelli, 2014 ), tumor cells (reviewed in Tkach and Thery, 2016 ; Wendler et al, 2016 ) and mesenchymal stromal/stem cells (reviewed in Bruno et al, 2015 ; Lener et al, 2015 ; Stephen et al, 2016 ).…”

Section: Pathogen–host Communication: Sending Messages Via Extracellumentioning

confidence: 99%

Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview

et al. 2018

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Recently, the interest in extracellular vesicles (EVs) released by pathogens like bacteria, fungi, and parasites has rapidly increased. Many of these pathogens actively modulate the immune responses of their host and there is accumulating evidence that pathogen-derived EV contribute to this process. The effects of pathogen-derived EV on the host immune system have been attributed to proteins, lipids, nucleic acids, and glycans contained in, or present on these EV. For example, toxins in bacterial EV can modulate pathogen clearance and antigen presentation, while EV-associated polysaccharides are potential vaccine targets because they induce protective immune responses. Furthermore, parasite EV-associated microRNA may increase parasite survival via host gene repression, and the lipid A moiety of LPS in bacteria-derived EV induces strong pro-inflammatory responses. Research on pathogen EV-associated molecules may pave new avenues to combat infectious diseases by immune intervention. This review provides an overview of the current knowledge of EV-associated molecules released by extracellular pathogens and their effects on the host immune system. The current focus and future hotspots of this rapidly expanding field will be highlighted and discussed.

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“…It is generally recognized that MSCs exert their therapeutic effects via the secretion of paracrine factors and stimulation of host cells rather than via direct engraftment and cell replacement, and there is increasing evidence for the significance of MSC-derived extracellular vesicles (EVs) in this context [ 15 , 16 ]. EVs are small phospholipid vesicles released from a wide variety of cell types, which are commonly classified into exosomes (30–100 nm; intraluminal vesicles originating from multivesicular bodies), microvesicles (100–1000 nm, released from the plasma membrane), and apoptotic bodies (1–5 µm) according to their biogenesis and size.…”

Section: Therapeutic Relevance Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Dynamic Cultivation of Mesenchymal Stem Cell Aggregates

et al. 2018

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Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates.

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Mesenchymal stromal cells as multifunctional cellular therapeutics – a potential role for extracellular vesicles

Cited by 31 publications

References 65 publications

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies forIn VivoTracking and Biodistribution Analysis

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies forIn VivoTracking and Biodistribution Analysis

Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview

Dynamic Cultivation of Mesenchymal Stem Cell Aggregates

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