scholarly journals Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo

2020 ◽  
Vol 10 (8) ◽  
Author(s):  
Athanasia Warnecke ◽  
Jennifer Harre ◽  
Hinrich Staecker ◽  
Nils Prenzler ◽  
Dirk Strunk ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Multipotent Stromal Cells ◽  
Noise Trauma

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

scholarly journals Some Special Aspects of Liver Repair after Resection and Administration of Multipotent Stromal Cells in Experiment

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 66
Author(s):  
Igor Maiborodin ◽  
Elena Lushnikova ◽  
Marina Klinnikova ◽  
Swetlana Klochkova
Keyword(s):  
Bone Marrow ◽  
Liver Resection ◽  
Connective Tissue ◽  
Light Microscopy ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Multipotent Stromal Cells ◽  
Rapid Restoration ◽  
Bone Marrow Origin

Changes in rat liver after resection and injection of autologous multipotent mesenchymal stromal cells of bone marrow origin (MSCs) transfected with the GFP gene and cell membranes stained with red-fluorescent lipophilic membrane dye were studied by light microscopy. It was found that after the introduction of MSCs into the damaged liver, their differentiation into any cells was not found. However, under the conditions of MSCs use, the number of neutrophils in the parenchyma normalizes earlier, and necrosis and hemorrhages disappear more quickly. It was concluded that the use of MSCs at liver resection for the rapid restoration of an organ is inappropriate, since the injected cells in vivo do not differentiate either into hepatocytes, into epithelial cells of bile capillaries, into endotheliocytes and pericytes of the vascular membranes, into fibroblasts of the scar or other connective tissue structures, or into any other cells present in the liver.

scholarly journals In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche

2018 ◽  
Vol 22 (2) ◽  
pp. 262-276.e7 ◽  
Author(s):  
Martin Breitbach ◽  
Kenichi Kimura ◽  
Tiago C. Luis ◽  
Christopher J. Fuegemann ◽  
Petter S. Woll ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Niche ◽  
Multipotent Stromal Cells ◽  
In Vivo Labeling ◽  
Endothelial Heterogeneity

scholarly journals Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

2020 ◽  
Vol 21 (3) ◽  
pp. 799 ◽  
Author(s):  
Joanna Lelek ◽  
Ewa K. Zuba-Surma
Keyword(s):  
Adipose Tissue ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Differentiation Potential

Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

The Globoseries Glycosphingolipid SSEA-4 Is a Marker of Bone Marrow-Derived Clonal Multipotent Stromal Cells In Vitro and In Vivo

2013 ◽  
Vol 22 (9) ◽  
pp. 1387-1397 ◽  
Author(s):  
Michael Rosu-Myles ◽  
Jennifer McCully ◽  
Joel Fair ◽  
Jelica Mehic ◽  
Pablo Menendez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Multipotent Stromal Cells

scholarly journals miR-4732-3p in Extracellular Vesicles From Mesenchymal Stromal Cells Is Cardioprotective During Myocardial Ischemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Rafael Sánchez-Sánchez ◽  
Marta Gómez-Ferrer ◽  
Ignacio Reinal ◽  
Marc Buigues ◽  
Estela Villanueva-Bádenas ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Transforming Growth Factor Beta ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Lentiviral Vector ◽  
Glucose Deprivation ◽  
Scar Tissue

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are an emerging alternative to cell-based therapies to treat many diseases. However, the complexity of producing homogeneous populations of EVs in sufficient amount hampers their clinical use. To address these limitations, we immortalized dental pulp-derived MSC using a human telomerase lentiviral vector and investigated the cardioprotective potential of a hypoxia-regulated EV-derived cargo microRNA, miR-4732-3p. We tested the compared the capacity of a synthetic miR-4732-3p mimic with EVs to confer protection to cardiomyocytes, fibroblasts and endothelial cells against oxygen-glucose deprivation (OGD). Results showed that OGD-induced cardiomyocytes treated with either EVs or miR-4732-3p showed prolonged spontaneous beating, lowered ROS levels, and less apoptosis. Transfection of the miR-4732-3p mimic was more effective than EVs in stimulating angiogenesis in vitro and in vivo and in reducing fibroblast differentiation upon transforming growth factor beta treatment. Finally, the miR-4732-3p mimic reduced scar tissue and preserved cardiac function when transplanted intramyocardially in infarcted nude rats. Overall, these results indicate that miR-4732-3p is regulated by hypoxia and exerts cardioprotective actions against ischemic insult, with potential application in cell-free-based therapeutic strategies.

scholarly journals In Vitro Study of Extracellular Vesicles Migration in Cartilage-Derived Osteoarthritis Samples Using Real-Time Quantitative Multimodal Nonlinear Optics Imaging

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 734
Author(s):  
Leonardo Mortati ◽  
Laura de Girolamo ◽  
Carlotta Perucca Orfei ◽  
Marco Viganò ◽  
Marco Brayda-Bruno ◽  
...  
Keyword(s):  
Real Time ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Second Harmonic ◽  
Time Lapse ◽  
Cartilage Explants ◽  
Innovative Technology

Mesenchymal stromal cells (MSCs)-derived extracellular vesicles (EVs) are promising therapeutic nano-carriers for the treatment of osteoarthritis (OA). The assessment of their uptake in tissues is mandatory but, to date, available technology does not allow to track and quantify incorporation in real-time. To fill this knowledge gap, the present study was intended to develop an innovative technology to determine kinetics of fluorescent MSC-EV uptake by means of time-lapse quantitative microscopy techniques. Adipose-derived mesenchymal stromal cells (ASCs)-EVs were fluorescently labeled and tracked during their uptake into chondrocytes micromasses or cartilage explants, both derived from OA patients. Immunofluorescence and time-lapse coherent anti-Stokes Raman scattering, second harmonic generation and two-photon excited fluorescence were used to follow and quantify incorporation. EVs penetration appeared quickly after few minutes and reached 30–40 μm depth after 5 h in both explants and micromasses. In explants, uptake was slightly faster, with EVs signal overlapping both extracellular matrix and chondrocytes, whereas in micromasses a more homogenous diffusion was observed. The finding of this study demonstrates that this innovative technology is a powerful tool to monitor EVs migration in tissues characterized by a complex extracellular network, and to obtain data resembling in vivo conditions.

scholarly journals Extracellular Vesicles from Adipose-Derived Mesenchymal Stem/Stromal Cells Accelerate Migration and Activate AKT Pathway in Human Keratinocytes and Fibroblasts Independently of miR-205 Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Andrea da Fonseca Ferreira ◽  
Pricila da Silva Cunha ◽  
Virgínia Mendes Carregal ◽  
Priscila de Cássia da Silva ◽  
Marcelo Coutinho de Miranda ◽  
...  
Keyword(s):  
Wound Healing ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Average Diameter ◽  
Skin Wound ◽  
Akt Pathway ◽  
Skin Wound Healing ◽  
Akt Phosphorylation ◽  
Akt Activation

Mesenchymal stem/stromal cells (MSCs) are promising tools in cell therapy. They secrete extracellular vesicles (EVs) that carry different classes of molecules that can promote skin repair, but the mechanisms are poorly understood. Skin wound healing is a complex process that requires the activity of several signaling pathways and cell types, including keratinocytes and fibroblasts. In this study, we explored whether adipose tissue MSC-derived EVs could accelerate migration and proliferation of keratinocytes and fibroblasts, activate the AKT pathway, and promote wound healing in vivo. Furthermore, we evaluated if EV effects are miR-205 dependent. We found that MSC EVs had an average diameter of 135 nm. Keratinocytes and fibroblasts exposed to EVs exhibited higher levels of proliferation, migration, and AKT activation. Topical administration of EVs accelerated skin wound closure. Knockdown of miR-205 decreased AKT phosphorylation in fibroblasts and keratinocytes, whereas migration was decreased only in keratinocytes. Moreover, knockdown of miR-205 failed to inhibit AKT phosphorylation in fibroblasts and keratinocytes exposed to EVs. About the mechanism of EV effects, we found that incubation with EVs prevented inhibition of AKT activation by miR-205 knockdown, suggesting that EVs activate AKT independently of miR-205. In conclusion, we demonstrated that EVs are a promising tool for wound healing.

scholarly journals Short-Term Exposure of Multipotent Stromal Cells to Low Oxygen Increases Their Expression of CX3CR1 and CXCR4 and Their Engraftment In Vivo

PLoS ONE ◽  
2007 ◽  
Vol 2 (5) ◽  
pp. e416 ◽  
Author(s):  
Shih-Chieh Hung ◽  
Radhika R. Pochampally ◽  
Shu-Ching Hsu ◽  
Cecelia Sanchez ◽  
Sy-Chi Chen ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Multipotent Stromal Cells ◽  
Low Oxygen ◽  
Short Term ◽  
Short Term Exposure
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