Uncovering the secretes of mesenchymal stem cells

Lavoie, Jessie R.; Rosu‐Myles, Michael

doi:10.1016/j.biochi.2013.06.017

Cited by 158 publications

(112 citation statements)

References 88 publications

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“…Extracellular particles and soluble factors are important mechanisms underlying MSC therapy. 37,40,47,100 Extracellular particles include released smaller more homogenous exosomes of endocytic origin and rather heterogeneous microvesicles by the outward budding and fission of the plasma membrane. 26,40 In our present study, we focused on exosomes and did not compare the exosomes with the non-exosomal fraction of the media.…”

Section: Discussionmentioning

confidence: 99%

“…37,40,47,100 Extracellular particles include released smaller more homogenous exosomes of endocytic origin and rather heterogeneous microvesicles by the outward budding and fission of the plasma membrane. 26,40 In our present study, we focused on exosomes and did not compare the exosomes with the non-exosomal fraction of the media. Our first step was to investigate whether treatment of TBI solely with exosomes derived from MSCs provides significant functional benefit compared to the PBS treatment, which is an unexplored area in the TBI field.…”

Section: Discussionmentioning

confidence: 99%

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Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury

Zhang¹,

Chopp

Meng³

et al. 2015

JNS

575

453

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Object Transplanted multipotent mesenchymal stromal cells (MSCs) improve functional recovery in rats after traumatic brain injury (TBI). Here, we test a novel hypothesis that systemic administration of cell-free exosomes generated from MSCs promotes functional recovery and neurovascular remodeling in rats after TBI. Methods Wistar rats were subjected to TBI followed by tail vein injection of 100 μg protein of exosomes derived from MSCs or an equal volume of vehicle phosphate-buffered saline (n = 8/group) 24 hours later. To evaluate cognitive and sensorimotor functional recovery, the modified Morris water maze, neurological severity score and footfault tests were performed. Animals were sacrificed at 35 days after TBI. Histopathological and immunohistochemical analyses were performed for measurements of lesion volume, neurovascular remodeling (angiogenesis and neurogenesis), and neuroinflammation. Results Compared with saline-treated controls, exosome-treated TBI rats showed significant improvement in spatial learning at 34-35 days measured by the Morris water maze test (p < 0.05), and sensorimotor functional recovery, i.e., reduced neurological deficits and footfault frequency, observed at 14-35 days post injury (p < 0.05). Exosome treatment significantly increased the number of newborn endothelial cells in the lesion boundary zone and dentate gyrus, and significantly increased the number of newborn immature and mature neurons in the dentate gyrus as well as reduced neuroinflammation. Conclusions We, for the first time, demonstrate that MSC-generated exosomes effectively improve functional recovery, at least in part, by promoting endogenous angiogenesis and neurogenesis and reducing inflammation in rats after TBI. Thus, MSC-generated exosomes may provide a novel cell-free therapy for TBI and possibly other neurological diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury

Zhang¹,

Chopp

Meng³

et al. 2015

JNS

575

453

View full text Add to dashboard Cite

show abstract

“…Through many investigations, MSCs have been shown to enhance tissue repair, which was achieved either by direct cell engraftment to the injury site or by indirect paracrine secretion of soluble factors and extracellular vesicles (exosomes and microvesicles) including mRNA and miRNA [1e3]. Currently, it is believed that the therapeutic effects of MSCs depend mainly on paracrine activity because engrafted MSCs are short-lived, which does not correlate with the success of MSC therapy [1,3]. To enhance the therapeutic efficacy of MSCs, many genetic engineering approaches have been explored, with the purpose to enhance homing ability toward injury sites, survivability in hostile in vivo conditions, and differentiation to the targeted lineages [2,4].…”

Section: Introductionmentioning

confidence: 99%

Minicircle microporation-based non-viral gene delivery improved the targeting of mesenchymal stem cells to an injury site

et al. 2016

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“…5,6 Literature findings indicate that ASCs exert their action through paracrine activity rather than through engraftment. [7][8][9] Furthermore, this paracrine activity is mediated by the release of membrane vesicles, such as exosomes. 10 These vesicles are from 30 nm to 100 nm in size and are of endosomal origin; 11 for this reason, they contain typical endosome-associated proteins, such as tetraspanin, alix, and heat-shock proteins, some of which are used as specific and quantitative endosomal markers.…”

mentioning

confidence: 99%

Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes

Busato

Bonafede

Bontempi

et al. 2016

IJN

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Purpose Recent findings indicate that the beneficial effects of adipose stem cells (ASCs), reported in several neurodegenerative experimental models, could be due to their paracrine activity mediated by the release of exosomes. The aim of this study was the development and validation of an innovative exosome-labeling protocol that allows to visualize them with magnetic resonance imaging (MRI). Materials and methods At first, ASCs were labeled using ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, 4–6 nm), and optimal parameters to label ASCs in terms of cell viability, labeling efficiency, iron content, and magnetic resonance (MR) image contrast were investigated. Exosomes were then isolated from labeled ASCs using a standard isolation protocol. The efficiency of exosome labeling was assessed by acquiring MR images in vitro and in vivo as well as by determining their iron content. Transmission electron microscopy images and histological analysis were performed to validate the results obtained. Results By using optimized experimental parameters for ASC labeling (200 µg Fe/mL of USPIO and 72 hours of incubation), it was possible to label 100% of the cells, while their viability remained comparable to unlabeled cells; the detection limit of MR images was of 10 2 and 2.5×10 3 ASCs in vitro and in vivo, respectively. Exosomes isolated from previously labeled ASCs retain nanoparticles, as demonstrated by transmission electron microscopy images. The detection limit by MRI was 3 µg and 5 µg of exosomes in vitro and in vivo, respectively. Conclusion We report a new approach for labeling of exosomes by USPIO that allows detection by MRI while preserving their morphology and physiological characteristics.

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Uncovering the secretes of mesenchymal stem cells

Cited by 158 publications

References 88 publications

Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury

Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury

Minicircle microporation-based non-viral gene delivery improved the targeting of mesenchymal stem cells to an injury site

Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes

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