scholarly journals Extracellular Vesicle-Shuttled mRNA in Mesenchymal Stem Cell Communication

Stem Cells ◽  
2017 ◽  
Vol 35 (4) ◽  
pp. 1093-1105 ◽  
Author(s):  
Enrico Ragni ◽  
Federica Banfi ◽  
Mario Barilani ◽  
Alessandro Cherubini ◽  
Valentina Parazzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Communication ◽  
Extracellular Vesicle

Umbilical Mesenchymal Stem Cell-Derived Extracellular Vesicle Conditioning Has an Immunosuppressive Effect on NK Cells

2021 ◽  
Author(s):  
G. Dostert ◽  
V. Jouan-Hureaux ◽  
H. Louis ◽  
É. Velot
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Nk Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Cell Communication ◽  
K562 Cells ◽  
Cell Cytotoxicity ◽  
Nk Cell Cytotoxicity

Background: In peripheral blood, human natural killer (NK) cells are immunological cells that nearly don’t express the ectonucleotidase CD73 on their plasma membrane. When exposed to mesenchymal stem cells (MSCs), NK cells are able to acquire CD73. MSCs are known to be CD73-positive (CD73+) and also to modulate the immune system, e.g. through adenosynergic pathway by ectonucleosidases, such as CD73. Extracellular vesicles (EVs) are involved in cell-to-cell communication. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as paracrine mediators that are part of MSC immunomodulatory effects including immunosuppressive properties and immune privilege. Objective: The aim of our work was to study if CD73 could be acquired by NK cells through cell-to-cell communication with MSC-EVs as cell culture additives. We also hypothesised that MSC-EVs would act as tolerance inducers to attenuate NK cell cytotoxicity. Methods: Cell isolation was made from human umbilical cords for MSCs and from human peripheral blood for NK cells. MSC-EVs were isolated by ultracentrifugation and filtration, then characterized by nanoparticle tracking assay and flow cytometry (CD9, 63, 81 and 73). MSC-EV interaction with NK cells was monitored by PKH67 staining. NK cell activation was followed by measuring the expression of CD73 and NK-activating receptor natural-killer group 2, member D (NKG2D) by flow cytometry. The cytotoxicity of NK cells or EV-conditioned NK cells was evaluated after co-culture with K562 cells. Results: We showed that MSC-EVs are nanoparticles able to express CD73 and interact with NK cells. MSC-EV conditioned NK cells seem to increase CD73 and decrease NKG2D through an EV-mediated mechanism. MSC-EVs have an immunosuppressive effect on NK cells by preventing NK cell activation and NK cell cytotoxicity towards K562 cells. Conclusions: Our results demonstrate that MSC-EVs could influence NK cell behaviour and act as immunosuppressant cell-based products.

Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke

2020 ◽  
Vol 62 ◽  
pp. 101106 ◽  
Author(s):  
Abolfazl Rahmani ◽  
Kiarash Saleki ◽  
Nima Javanmehr ◽  
Javad Khodaparast ◽  
Payam Saadat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicle

scholarly journals Monocyte mimics improve mesenchymal stem cell-derived extracellular vesicle homing in a mouse MI/RI model

Biomaterials ◽  
2020 ◽  
Vol 255 ◽  
pp. 120168 ◽  
Author(s):  
Ning Zhang ◽  
Yanan Song ◽  
Zheyong Huang ◽  
Jing Chen ◽  
Haipeng Tan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicle

scholarly journals Glioblastoma-mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow

2015 ◽  
Vol 89 (4) ◽  
pp. 365-375 ◽  
Author(s):  
Micheli M. Pillat ◽  
Mona N. Oliveira ◽  
Helena Motaln ◽  
Barbara Breznik ◽  
Talita Glaser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Information Flow ◽  
Expression Patterns ◽  
Cell Communication ◽  
Kinin Receptors

scholarly journals Diameters and Fluorescence Calibration for Extracellular Vesicle Analyses by Flow Cytometry

2020 ◽  
Vol 21 (21) ◽  
pp. 7885 ◽  
Author(s):  
Pasquale Simeone ◽  
Christian Celia ◽  
Giuseppina Bologna ◽  
Eva Ercolino ◽  
Laura Pierdomenico ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Crucial Role ◽  
Therapeutic Option ◽  
Extracellular Vesicle ◽  
Clinical Settings ◽  
Concentration Measurements ◽  
High Level

Extracellular vesicles (EVs) play a crucial role in the intercellular crosstalk. Mesenchymal stem cell-derived EVs (MSC-EVs), displaying promising therapeutic roles, contribute to the strong rationale for developing EVs as an alternative therapeutic option. EV analysis still represents one of the major issues to be solved in order to translate the use of MSC-EV detection in clinical settings. Even if flow cytometry (FC) has been largely applied for EV studies, the lack of consensus on protocols for FC detection of EVs generated controversy. Standard FC procedures, based on scatter measurements, only allows the detection of the “tip of the iceberg” of all EVs. We applied an alternative FC approach based on the use of a trigger threshold on a fluorescence channel. The EV numbers obtained by the application of the fluorescence triggering resulted significantly higher in respect to them obtained from the same samples acquired by placing the threshold on the side scatter (SSC) channel. The analysis of EV concentrations carried out by three different standardized flow cytometers allowed us to achieve a high level of reproducibility (CV < 20%). By applying the here-reported method highly reproducible results in terms of EV analysis and concentration measurements were obtained.

scholarly journals CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Zuowei Shi ◽  
Kaifu Wang ◽  
Yufei Xing ◽  
Xuefeng Yang
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Therapeutic Potential ◽  
Extracellular Vesicle ◽  
Loss Of Function ◽  
Osteosarcoma Cells ◽  
Tissue Samples ◽  
Cell Phenotypes

Emerging evidence indicates that extracellular vesicle (EV)-encapsulated circRNAs have the potential diagnostic and prognostic values for malignancies. However, the role of circNRIP1 in osteosarcoma remains unclear. We herein investigated the therapeutic potential of circNRIP1 delivered by bone marrow mesenchymal stem cell–derived EVs (BMSC-EVs) in osteosarcoma. The expression of circNRIP1 was examined in the clinical tissue samples of osteosarcoma patients, after which the downstream genes of circNRIP1 were bioinformatically predicted. Gain- and loss-of function assays were then performed in osteosarcoma cells with manipulation of circNRIP1 and miR-532-3p expression. EVs isolated from BMSCs were characterized and co-cultured with osteosarcoma cells to examine their effects on cell phenotypes, as reflected by CCK-8 and Transwell assays. Further, a mouse model of tumor xenografts was established for in vivo substantiation. circNRIP1 was upregulated in osteosarcoma tissues and cells. Overexpression of circNRIP1 promoted the proliferative, migratory, and invasive potential of osteosarcoma cells. Co-culture data showed that BMSC-EVs could transfer circNRIP1 into osteosarcoma cells where it competitively bound to miR-532-3p and weakened miR-532-3p’s binding ability to AKT3. By this mechanism, the PI3K/AKT signaling pathway was activated and the malignant characteristics of osteosarcoma cells were stimulated. In vivo experimental results unveiled that circNRIP1-overexpressing BMSC-EVs in nude mice resulted in enhanced tumor growth. In conclusion, the BMSC-EV-enclosed circNRIP1 revealed a new molecular mechanism in the pathogenesis of osteosarcoma, which might provide a novel therapeutic target for osteosarcoma.

A scalable coaxial bioprinting technology for mesenchymal stem cell microfiber fabrication and high extracellular vesicle yield

2021 ◽  
Author(s):  
Jianwei Chen ◽  
Duchao Zhou ◽  
Zhenguo Nie ◽  
Liang Lu ◽  
Zhidong Lin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicle ◽  
Core Shell ◽  
Protein Profiles ◽  
Liquid Chromatography Mass Spectrometry ◽  
Culture Dish ◽  
Unique Protein ◽  
3D Environments ◽  
Scalable Methods

Abstract Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising candidates for regenerative medicine; however, the lack of scalable methods for high quantity EV production limits their application. In addition, signature EV-derived proteins shared in 3D environments and 2D surfaces, remain mostly unknown. Herein, we present a platform combining MSC microfiber culture with ultracentrifugation purification for high EV yield. Within this platform, a high quantity MSC solution (~3x10^8 total cells) is encapsulated in a meter-long hollow hydrogel-microfiber via coaxial bioprinting technology. In this 3D core-shell microfiber environment, MSCs express higher levels of stemness markers (Oct4, Nanog, Sox2) than in 2D culture, and maintain their differentiation capacity. Moreover, this platform enriches particles by ~1009-fold compared to conventional 2D culture, while preserving their pro-angiogenic properties. Liquid chromatography-mass spectrometry characterization results demonstrate that EVs derived from our platform and conventional 2D culturing have unique protein profiles with 3D-EVs having a greater variety of proteins (1023 vs 605), however, they also share certain proteins (536) and signature MSC-EV proteins (10). This platform, therefore, provides a new tool for EV production using microfibers in one culture dish, thereby reducing space, labor, time, and cost.

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