scholarly journals High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1292
Author(s):  
Kyung Min Lim ◽  
Ahmed Abdal Dayem ◽  
Yujin Choi ◽  
Yoonjoo Lee ◽  
Jongyub An ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Dermal Fibroblasts ◽  
Orbicularis Oculi Muscle ◽  
Ocular Surgery ◽  
Paracrine Factors ◽  
Orbicularis Oculi ◽  
Antioxidant Genes ◽  
Adult Mesenchymal Stem Cells

Extracellular vesicles (EVs) are paracrine factors that mediate stem cell therapeutics. We aimed at evaluating the possible therapeutic and esthetic applications of EVs prepared from the waste human facial tissue-derived orbicularis oculi muscle stem cells (OOM-SCs). OOM-SCs were isolated from the ocular tissues (from elders and youngsters) after upper eyelid blepharoplasty or epiblepharon surgeries. EVs were prepared from the OOM-SCs (OOM-SC-EVs) and their three-dimensional spheroids. OOM-SCs showed a spindle-like morphology with trilineage differentiation capacity, positive expression of CD105, CD 90, and CD73, and negative expression of CD45 and CD34, and their stem cell properties were compared with other adult mesenchymal stem cells. OOM-SC-EVs showed a high inhibitory effect on melanin synthesis in B16F10 cells by blocking tyrosinase activity. OOM-SC-EVs treatment led to a significant attenuation of senescence-associated changes, a decrease in reactive oxygen species generation, and an upregulation of antioxidant genes. We demonstrated the regeneration activity of OOM-SC-EVs in in vitro wound healing of normal human dermal fibroblasts and upregulation of anti-wrinkle-related genes and confirmed the therapeutic potential of OOM-SC-EVs in the healing of the in vivo wound model. Our study provides promising therapeutic and esthetic applications of OOM-SC-EVs, which can be obtained from the ocular surgery-derived waste human facial tissues.

scholarly journals Mesenchymal Stem Cells Do Not Lose Direct Labels Including Iron Oxide Nanoparticles and DFO-89Zr Chelates through Secretion of Extracellular Vesicles

Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 484
Author(s):  
Yue Gao ◽  
Anna Jablonska ◽  
Chengyan Chu ◽  
Piotr Walczak ◽  
Miroslaw Janowski
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Extracellular Vesicles ◽  
Superparamagnetic Iron Oxide ◽  
Cell Labeling ◽  
Oxide Nanoparticles ◽  
Stem Cell Delivery ◽  
Cellular Labeling

Rapidly ageing populations are beset by tissue wear and damage. Stem cell-based regenerative medicine is considered a solution. Years of research point to two important aspects: (1) the use of cellular imaging to achieve sufficient precision of therapeutic intervention, and the fact that (2) many therapeutic actions are executed through extracellular vesicles (EV), released by stem cells. Therefore, there is an urgent need to interrogate cellular labels in the context of EV release. We studied clinically applicable cellular labels: superparamagnetic iron oxide nanoparticles (SPION), and radionuclide detectable by two main imaging modalities: MRI and PET. We have demonstrated effective stem cell labeling using both labels. Then, we obtained EVs from cell cultures and tested for the presence of cellular labels. We did not find either magnetic or radioactive labels in EVs. Therefore, we report that stem cells do not lose labels in released EVs, which indicates the reliability of stem cell magnetic and radioactive labeling, and that there is no interference of labels with EV content. In conclusion, we observed that direct cellular labeling seems to be an attractive approach to monitoring stem cell delivery, and that, importantly, labels neither locate in EVs nor affect their basic properties.

scholarly journals Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles

2020 ◽  
Vol 9 (1) ◽  
pp. 1807674 ◽  
Author(s):  
Thomas E. Whittaker ◽  
Anika Nagelkerke ◽  
Valeria Nele ◽  
Ulrike Kauscher ◽  
Molly M. Stevens
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Paracrine Factors

scholarly journals Glutathione–Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair

2020 ◽  
Vol 21 (5) ◽  
pp. 1638 ◽  
Author(s):  
Emilia Di Giovanni ◽  
Silvia Buonvino ◽  
Ivano Amelio ◽  
Sonia Melino
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Tissue Repair ◽  
Dermal Fibroblasts ◽  
Water Soluble ◽  
Dependent Manner ◽  
Tissue Repair And Regeneration ◽  
Stem Cell Delivery ◽  
Cell Based Therapy

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.

scholarly journals Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells

Theranostics ◽  
2019 ◽  
Vol 9 (23) ◽  
pp. 6976-6990 ◽  
Author(s):  
Yan Zhang ◽  
Jia Xu ◽  
Siying Liu ◽  
Meikuang Lim ◽  
Shuang Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Therapeutic Effect ◽  
Extracellular Vesicles ◽  
Embryonic Stem

scholarly journals Extracellular Vesicles: Evolving Factors in Stem Cell Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Muhammad Nawaz ◽  
Farah Fatima ◽  
Krishna C. Vallabhaneni ◽  
Patrice Penfornis ◽  
Hadi Valadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cell Biology ◽  
Trophic Factors ◽  
Stem Cell Biology ◽  
Cell Fates ◽  
Bidirectional Communication

Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

scholarly journals VEGF is critical for stem cell-mediated cardioprotection and a crucial paracrine factor for defining the age threshold in adult and neonatal stem cell function

2008 ◽  
Vol 295 (6) ◽  
pp. H2308-H2314 ◽  
Author(s):  
Troy A. Markel ◽  
Yue Wang ◽  
Jeremy L. Herrmann ◽  
Paul R. Crisostomo ◽  
Meijing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Myocardial Recovery ◽  
Paracrine Factors

Bone marrow mesenchymal stem cells (MSCs) may be a novel treatment modality for organ ischemia, possibly through the release of beneficial paracrine factors. However, an age threshold likely exists as to when MSCs gain their beneficial protective properties. We hypothesized that 1) VEGF would be a crucial stem cell paracrine mediator in providing postischemic myocardial protection and 2) small-interfering (si)RNA ablation of VEGF in adult MSCs (aMSCs) would equalize the differences observed between aMSC- and neonatal stem cell (nMSC)-mediated cardioprotection. Female adult Sprague-Dawley rat hearts were subjected to ischemia-reperfusion injury via Langendorff-isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). MSCs were harvested from adult and 2.5-wk-old neonatal mice and cultured under normal conditions. VEGF was knocked down in both cell lines by VEGF siRNA. Immediately before ischemia, one million aMSCs or nMSCs with or without VEGF knockdown were infused into the coronary circulation. The cardiac functional parameters were recorded. VEGF in cell supernatants was measured via ELISA. aMSCs produced significantly more VEGF than nMSCs and were noted to increase postischemic myocardial recovery compared with nMSCs. The knockdown of VEGF significantly decreased VEGF production in both cell lines, and the pretreatment of these cells impaired stem cell-mediated myocardial function. The knockdown of VEGF in adult stem cells equalized the myocardial functional differences observed between adult and neonatal stem cells. Therefore, VEGF is a critical paracrine mediator in facilitating postischemic myocardial recovery and likely plays a role in mediating the observed age threshold during stem cell therapy.

scholarly journals Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Melissa Lo Monaco ◽  
Greet Merckx ◽  
Jessica Ratajczak ◽  
Pascal Gervois ◽  
Petra Hilkens ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Outcome Measures ◽  
Cartilage Repair ◽  
Cartilage Tissue ◽  
Preclinical Studies ◽  
Paracrine Factors ◽  
Advantages And Disadvantages

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recentin vitrodata and fromin vivopreclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

scholarly journals Multifaced Roles of the Urokinase System in the Regulation of Stem Cell Niches

Acta Naturae ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 19-32 ◽  
Author(s):  
K. V. Dergilev ◽  
V. V. Stepanova ◽  
I. B. Beloglazova ◽  
Z. I. Tsokolayeva ◽  
E. V. Parfenova
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Biologically Active ◽  
Tissue Cell ◽  
Direct Cell ◽  
Urokinase System ◽  
And Migration ◽  
Stem Cell Niches

Proliferation, subsequent migration to the damaged area, differentiation into appropriate cell types, and/or secretion of biologically active molecules and extracellular vesicles are important processes that underlie the involvement of stem/progenitor cells in the repair and regeneration of tissues and organs. All these functions are regulated through the interaction between stem cells and the microenvironment in the tissue cell niches that control these processes through direct cell-cell interactions, production of the extracellular matrix, release of extracellular vesicles, and secretion of growth factors, cytokines, chemokines, and proteases. One of the most important proteolytic systems involved in the regulation of cell migration and proliferation is the urokinase system represented by the urokinase plasminogen activator (uPA, urokinase), its receptor (uPAR), and inhibitors. This review addresses the issues of urokinase system involvement in the regulation of stem cell niches in various tissues and analyzes the possible effects of this system on the signaling pathways responsible for the proliferation, programmed cell death, phenotype modulation, and migration properties of stem cells.

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