Dynamics of plasma membrane surface related to the release of extracellular vesicles by mesenchymal stem cells in culture

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

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Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽

10.3390/biomedicines9060667 ◽

2021 ◽

Vol 9 (6) ◽

pp. 667

Author(s):

Gabriella Racchetti ◽

Jacopo Meldolesi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Responses ◽

Extracellular Vesicles ◽

Immune Regulation ◽

Great Increase ◽

The Body ◽

Cell Aging ◽

Therapeutic Effects ◽

Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

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Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

International Journal of Molecular Sciences ◽

10.3390/ijms22031375 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1375

Author(s):

María Carmen Carceller ◽

María Isabel Guillén ◽

María Luisa Gil ◽

María José Alcaraz

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Extracellular Vesicles ◽

Nuclear Factor Κb ◽

Peritoneal Macrophages ◽

Toll Like Receptor 4 ◽

Anti Inflammatory ◽

Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

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Extracellular vesicles from three dimensional culture of human placental mesenchymal stem cells ameliorated renal ischemia/reperfusion injury

The International Journal of Artificial Organs ◽

10.1177/0391398820986809 ◽

2021 ◽

pp. 039139882098680

Author(s):

Xuefeng Zhang ◽

Nan Wang ◽

Yuhua Huang ◽

Yan Li ◽

Gang Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Therapeutic Potential ◽

Expression Profiles ◽

Ischemia Reperfusion ◽

Three Dimensional ◽

3D Culture ◽

Placental Mesenchymal Stem Cells ◽

2D And 3D

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.

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Bone marrow mesenchymal stem cells-derived extracellular vesicles carrying microRNA-221-3p protect against ischemic stroke via ATF3

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.04.022 ◽

2021 ◽

Author(s):

Zhibing Ai ◽

Chaohui Cheng ◽

Lan Zhou ◽

Songhe Yin ◽

Lei Wang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Ischemic Stroke ◽

Extracellular Vesicles ◽

Marrow Mesenchymal Stem Cells

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INFLUENCE OF MESENCHYMAL STEM CELLS AND FIBRIN RICH PLASMA MEMBRANE TO REPAIR OSTEOCHONDRAL DEFECTS IN THE RABBIT KNEE

Cytotherapy ◽

10.1016/j.jcyt.2021.02.060 ◽

2021 ◽

Vol 23 (4) ◽

pp. 20

Author(s):

JA Villanova ◽

FM Oliveira ◽

JC Wenceslau ◽

DL Bona ◽

L Fracaro ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Plasma Membrane ◽

Osteochondral Defects ◽

Rabbit Knee

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Abstract 16849: Extracellular Vesicles Derived From Mesenchymal Stem Cells Protects Mice From Monocrotaline-Induced Pulmonary Hypertension and Improve Echocardiographic Parameters

Circulation ◽

10.1161/circ.142.suppl_3.16849 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Giana Blume Corssac ◽

Rayane Teixeira ◽

Catherine Karbasiafshar ◽

Olin D Liang ◽

Ruhul Abid

Keyword(s):

Stem Cells ◽

Pulmonary Hypertension ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

High Morbidity ◽

Ejection Time ◽

Pulmonary Vascular Remodeling ◽

Incurable Disease ◽

Echocardiographic Parameters ◽

Rv Function

Introduction: Pulmonary hypertension (PH) is a currently incurable disease with high morbidity and mortality. Treatment with extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) appeared to be effective and promising. Objective: We aimed at evaluating whether MSC-EVs could improve right ventricle (RV) and pulmonary artery (PA) functions in mice with PAH induced by monocrotaline (MCT). Methods: FVB mice (M/F – 6 weeks) received MCT injections 1x/week for 4 weeks (60mg/kg sc.) and were treated with MSCs-EVs 24 hours after each MCT injection (3x10 6 cells in 100μL PBS 1x, iv.). The experimental groups were: Control (vehicle-vehicle; n=9); MCT (MCT-vehicle; n=10); Control EVs (vehicle-EVs; n=8); MCT EVs (MCT-EVs; n=10); PA acceleration time (PAT), PA ejection time (PET) and tricuspid annular plane systolic excursion (TAPSE) were assessed by echocardiography 28 days after first MCT injection; Fulton index was used to calculate RV hypertrophy, and pulmonary vascular remodeling (WT/D) was assessed by histology. Results: PAT and PAT/PET were decreased by 22.6±5.7% and 15.6±4.9%, respectively, in MCT group compared to Control (p<0.01 and p<0.02). PAT was increased in Control EVs and MCT EVs groups when compared with MCT group (by 28.2±7.6%, p<0.01 and 20±6.9%, p<0.04, respectively). TAPSE (figure 1) was decreased in the MCT group compared with Control (42.9±6.7%, p<0.0001) and increased in both Control EVs (62.8±12.2%, p<0.0001) and MCT EVs (52.7±11.1%, p<0.0005) groups compared with MCT group. In addition, MCT group presented RV hypertrophy 49.4±16.5% higher than Control (p<0.03), and 29.1±10.4% higher than MCT EVs group (p<0.05). The WT/D was increased in MCT compared to Control (63.7±7.6%, p<0.0001), but decreased in Control EVs (44.9±4.6%, p<0.0001) and MCT EVs (44.3±5.4%, p<0.0001) in relation to MCT group. Conclusion: Treatment with MSC-EVs protects against the development of PH and improves PA and the RV function in MCT-treated mice.

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In Vivo Effects of Ozone on Rat Alveolar Macrophage Plasma Membrane Surface Sulfhydryl Groups

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1988.tb51423.x ◽

1988 ◽

Vol 529 (1 Fourth Colloq) ◽

pp. 73-74

Author(s):

J. E. RYER ◽

G. WITZ ◽

B. D. GOLDSTEIN ◽

M. A. AMORUSO

Keyword(s):

Plasma Membrane ◽

Alveolar Macrophage ◽

Membrane Surface ◽

Sulfhydryl Groups ◽

In Vivo Effects ◽

Plasma Membrane Surface

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Paracrystalline arrays of membrane-to-membrane cross bridges associated with the inner surface of plasma membrane

The Journal of Cell Biology ◽

10.1083/jcb.77.2.323 ◽

1978 ◽

Vol 77 (2) ◽

pp. 323-328 ◽

Cited By ~ 7

Author(s):

WW Franke ◽

C Grund ◽

E Schmid ◽

E Mandelkow

Keyword(s):

Plasma Membrane ◽

Plasma Membranes ◽

Cultured Cells ◽

Membrane Surface ◽

Hexagonal Lattice ◽

Interparticle Distance ◽

Macromolecular Complexes ◽

Inner Surface ◽

Cross Bridges ◽

Plasma Membrane Surface

In cultured cells of the rat kangaroo PtK2 line, veils of the cell surface were observed which consisted of only plasma membrane and paracrystalline arrays of membrane-associated particles sandwiched in between. These membrane-to-membrane cross-bridging 9-to 11-nm wide particles were somewhat coumellar-shaped and were arranged on a hexagonal lattice with an interparticle distance of 16nm. At higher magnification, they revealed an unstained core, thus suggesting a ringlike substructure. Similar arrays of paracrystal-containing veils, which were rather variable in size and frequency, were also observed in other cultured cells. It is hypothesized that these paracrystals represent protein macromolecular complexes associated with the inner plasma membrane surface which crystallize when plasma membranes come into close intracellular contact and other components of the subsurface network are removed.

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