Mesenchymal stem cell–derived extracellular vesicles: a new impetus of promoting angiogenesis in tissue regeneration

Shi, Ying‐Hong; Shi, Hui; Nomi, Adnan; Zhang, Leilei; Zhang, Bin; Qian, Hui

doi:10.1016/j.jcyt.2018.11.012

Cited by 46 publications

(29 citation statements)

References 94 publications

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“…Angiogenesis is a complex process that involves several consecutive steps (198) from endothelial cell proliferation and migration to tube formation, branching, and anastomosis (192,198). All these processes are modulated by the inflammatory microenvironment formed in previous stages (105).…”

Section: The Importance Of Angiogenesis In Stroke Recovery and Bbb Pementioning

confidence: 99%

“…All these processes are modulated by the inflammatory microenvironment formed in previous stages (105). Therefore, the induction of angiogenesis after an ischemic injury is mediated by the same stimuli that cause the pathologic BBB disruption (198). BECs are the primary effectors of the angiogenic response after ischemic injury, followed by the pericytes and smooth muscle cells (139).…”

Section: The Importance Of Angiogenesis In Stroke Recovery and Bbb Pementioning

confidence: 99%

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Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

et al. 2020

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The blood–brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting the brain from unwanted compounds, but its impairment is involved in a vast number of pathological conditions. Disruption of the BBB and increase in its permeability are key in the development of several neurological diseases and have been extensively studied in stroke. Ischemic stroke is the most prevalent type of stroke and is characterized by a myriad of pathological events triggered by an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). BBB permeability seems to follow a multiphasic pattern throughout the different stroke stages that have been associated with distinct biological substrates. In the hyperacute stage, sudden hypoxia damages the BBB, leading to cytotoxic edema and increased permeability; in the acute stage, the neuroinflammatory response aggravates the BBB injury, leading to higher permeability and a consequent risk of HT that can be motivated by reperfusion therapy; in the subacute stage (1–3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky BBB, but this permeability has been associated with improved clinical recovery. In the chronic stage (>6 weeks), an increase of BBB restoration factors leads the barrier to start decreasing its permeability. Nonetheless, permeability will persist to some degree several weeks after injury. Understanding the mechanisms behind BBB dysregulation and HT pathophysiology could potentially help guide acute stroke care decisions and the development of new therapeutic targets; however, effective translation into clinical practice is still lacking. In this review, we will address the different pathological and physiological repair mechanisms involved in BBB permeability through the different stages of ischemic stroke and their role in the development of HT and stroke recovery.

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Section: The Importance Of Angiogenesis In Stroke Recovery and Bbb Pementioning

confidence: 99%

Section: The Importance Of Angiogenesis In Stroke Recovery and Bbb Pementioning

confidence: 99%

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

et al. 2020

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“…[14][15][16][17] In their multifaceted role of modulating biological responses, the involvement of exosomes in angiogenesis has been documented and their therapeutic application potential in regeneration is increasingly being concerned. 18,19 Although previous study has demonstrated that dental pulp cell-derived exosomes possess angiogenic potential with possible therapeutic effects in regenerative endodontics. 20 Whether exosomes derived from transplanted SHED aggregates promote angiogenesis in pulp regeneration and the underlying mechanisms remain unclear, which urgently requires further exploration.…”

Section: Introductionmentioning

confidence: 99%

SHED aggregate exosomes shuttled miR‐26a promote angiogenesis in pulp regeneration via TGF‐β/SMAD2/3 signalling

Xuan

Liu

et al. 2021

Cell Proliferation

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“…Angiogenesis is the crucial need for tissue regeneration (Bi et al, 2012 ). MSC derived EVs have already developed for the new impetus for improving angiogenesis in tissue regeneration, and EVs derived from different types of MSCs have been demonstrated promoted angiogenesis (Shi et al, 2019 ). The EC migration results showed that PMSC-EVs significantly enhanced the migration of HUVECs compared to the control group ( Figures 2A,B ).…”

Section: Resultsmentioning

confidence: 99%

Extracellular Matrix Mimicking Nanofibrous Scaffolds Modified With Mesenchymal Stem Cell-Derived Extracellular Vesicles for Improved Vascularization

Hao

Swindell

Ramasubramanian

et al. 2020

Front. Bioeng. Biotechnol.

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The network structure and biological components of natural extracellular matrix (ECM) are indispensable for promoting tissue regeneration. Electrospun nanofibrous scaffolds have been widely used in regenerative medicine to provide structural support for cell growth and tissue regeneration due to their natural ECM mimicking architecture, however, they lack biological functions. Extracellular vesicles (EVs) are potent vehicles of intercellular communication due to their ability to transfer RNAs, proteins, and lipids, thereby mediating significant biological functions in different biological systems. Matrix-bound nanovesicles (MBVs) are identified as an integral and functional component of ECM bioscaffolds mediating significant regenerative functions. Therefore, to engineer EVs modified electrospun scaffolds, mimicking the structure of the natural EV-ECM complex and the physiological interactions between the ECM and EVs, will be attractive and promising in tissue regeneration. Previously, using one-bead one-compound (OBOC) combinatorial technology, we identified LLP2A, an integrin α4β1 ligand, which had a strong binding to human placenta-derived mesenchymal stem cells (PMSCs). In this study, we isolated PMSCs derived EVs (PMSC-EVs) and demonstrated they expressed integrin α4β1 and could improve endothelial cell (EC) migration and vascular sprouting in an ex vivo rat aortic ring assay. LLP2A treated culture surface significantly improved PMSC-EV attachment, and the PMSC-EV treated culture surface significantly enhanced the expression of angiogenic genes and suppressed apoptotic activity. We then developed an approach to enable "Click chemistry" to immobilize LLP2A onto the surface of electrospun scaffolds as a linker to immobilize PMSC-EVs onto the scaffold. The PMSC-EV modified electrospun scaffolds significantly promoted EC survival and angiogenic gene expression, such as KDR and TIE2, and suppressed the expression of Hao et al. Scaffolds Modified With Extracellular Vesicles apoptotic markers, such as caspase 9 and caspase 3. Thus, PMSC-EVs hold promising potential to functionalize biomaterial constructs and improve the vascularization and regenerative potential. The EVs modified biomaterial scaffolds can be widely used for different tissue engineering applications.

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Mesenchymal stem cell–derived extracellular vesicles: a new impetus of promoting angiogenesis in tissue regeneration

Cited by 46 publications

References 94 publications

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

SHED aggregate exosomes shuttled miR‐26a promote angiogenesis in pulp regeneration via TGF‐β/SMAD2/3 signalling

Extracellular Matrix Mimicking Nanofibrous Scaffolds Modified With Mesenchymal Stem Cell-Derived Extracellular Vesicles for Improved Vascularization

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