scholarly journals Extracellular Vesicles: The New Frontier of Stem Cell Regenerative Medicine?

2020 ◽  
Author(s):  
Maria Magdalena Barreca ◽  
Patrizia Cancemi ◽  
Fabiana Geraci
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Cell Communication ◽  
Self Healing ◽  
Combined Use ◽  
Organ Repair

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

scholarly journals Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine?

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1163 ◽  
Author(s):  
Maria Magdalena Barreca ◽  
Patrizia Cancemi ◽  
Fabiana Geraci
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Extracellular Vesicles ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Cell Communication ◽  
Self Healing ◽  
Induced Pluripotent

Regenerative medicine aims to repair damaged, tissues or organs for the treatment of various diseases, which have been poorly managed with conventional drugs and medical procedures. To date, multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self-healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects, especially for mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) in damaged tissue restore are not dependent on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release extracellular vesicles (EVs). EVs play a fundamental role in cell-to-cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms through which MSCs and iPSCs-derived EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

scholarly journals Cereblon-Based Small-Molecule Compounds to Control Neural Stem Cell Proliferation in Regenerative Medicine

2021 ◽  
Vol 9 ◽  
Author(s):  
Tomomi Sato ◽  
Takumi Ito ◽  
Hiroshi Handa
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Brain Size ◽  
Therapeutic Effects ◽  
Sedative Drug

Thalidomide, a sedative drug that was once excluded from the market owing to its teratogenic properties, was later found to be effective in treating multiple myeloma. We had previously demonstrated that cereblon (CRBN) is the target of thalidomide embryopathy and acts as a substrate receptor for the E3 ubiquitin ligase complex, Cullin-Ring ligase 4 (CRL4CRBN) in zebrafish and chicks. CRBN was originally identified as a gene responsible for mild intellectual disability in humans. Fetuses exposed to thalidomide in early pregnancy were at risk of neurodevelopmental disorders such as autism, suggesting that CRBN is involved in prenatal brain development. Recently, we found that CRBN controls the proliferation of neural stem cells in the developing zebrafish brain, leading to changes in brain size. Our findings imply that CRBN is involved in neural stem cell growth in humans. Accumulating evidence shows that CRBN is essential not only for the teratogenic effects but also for the therapeutic effects of thalidomide. This review summarizes recent progress in thalidomide and CRBN research, focusing on the teratogenic and therapeutic effects. Investigation of the molecular mechanisms underlying the therapeutic effects of thalidomide and its derivatives, CRBN E3 ligase modulators (CELMoDs), reveals that these modulators provide CRBN the ability to recognize neosubstrates depending on their structure. Understanding the therapeutic effects leads to the development of a novel technology called CRBN-based proteolysis-targeting chimeras (PROTACs) for target protein knockdown. These studies raise the possibility that CRBN-based small-molecule compounds regulating the proliferation of neural stem cells may be developed for application in regenerative medicine.

scholarly journals Tissue Regeneration without Stem Cell Transplantation: Self-Healing Potential from Ancestral Chemistry and Physical Energies

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Federica Facchin ◽  
Eva Bianconi ◽  
Silvia Canaider ◽  
Valentina Basoli ◽  
Pier Mario Biava ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Electromagnetic Fields ◽  
Tissue Regeneration ◽  
Adult Stem Cells ◽  
Molecular Mechanisms ◽  
The Body ◽  
Self Healing ◽  
Mechanical Vibrations

The human body constantly regenerates after damage due to the self-renewing and differentiating properties of its resident stem cells. To recover the damaged tissues and regenerate functional organs, scientific research in the field of regenerative medicine is firmly trying to understand the molecular mechanisms through which the regenerative potential of stem cells may be unfolded into a clinical application. The finding that some organisms are capable of regenerative processes and the study of conserved evolutionary patterns in tissue regeneration may lead to the identification of natural molecules of ancestral species capable to extend their regenerative potential to human tissues. Such a possibility has also been strongly suggested as a result of the use of physical energies, such as electromagnetic fields and mechanical vibrations in human adult stem cells. Results from scientific studies on stem cell modulation confirm the possibility to afford a chemical manipulation of stem cell fate in vitro and pave the way to the use of natural molecules, as well as electromagnetic fields and mechanical vibrations to target human stem cells in their niche inside the body, enhancing human natural ability for self-healing.

scholarly journals Applications, challenges and prospects of mesenchymal stem cell exosomes in regenerative medicine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aysa Rezabakhsh ◽  
Emel Sokullu ◽  
Reza Rahbarghazi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Ethical Issues ◽  
Cell Communication ◽  
Cell Types ◽  
Therapeutic Approaches ◽  
Cell Therapies ◽  
Isolation And Purification ◽  
Direct Cell

AbstractRecent advances in the identification and application of different stem cell types have offered alternative therapeutic approaches for clinicians. The lack of successful engraftment, migration into the injured site, loss of functionality and viability, ethical issues, shortage of donated allogeneic stem cells and the possibility of transmission of infectious are the main challenges associated with direct cell transplantation. The discovery and research on exosomes have led to the rise of hopes for the alleviation of different pathologies in regenerative medicine. Exo are nano-sized extracellular vesicles (40–150 nm) and released by each type. These nanoparticles participate in cell-to-cell communication in a paracrine manner. It is thought that the application of Exo can circumvent several drawbacks related to whole-cell therapies. Because of their appropriate size and stability, Exo are touted as therapeutic bullets transferring signaling factors into the acceptor cells in a paracrine manner. Despite these advantages, technologies associated with Exo isolation and purification are challenging because of heterogeneity in exosomal size and cargo. The lack of standard GMP-grade protocols is the main hurdle that limits the extensive application of Exo in the clinical setting. Here, the authors aimed to inspire a logical and realistic vision about problems associated with Exo application in regenerative medicine.

scholarly journals Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 109
Author(s):  
Álvaro M. Martins ◽  
Cátia C. Ramos ◽  
Daniela Freitas ◽  
Celso A. Reis
Keyword(s):  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
De Novo ◽  
Recipient Cell ◽  
Cell Communication ◽  
Cancer Biomarkers ◽  
Functional Roles ◽  
Molecular Information ◽  
Glycosylation Pathway ◽  
Organ Tropism

Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.

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 Stem Cell-Derived Exosomes in Autism Spectrum Disorder

2020 ◽  
Vol 17 (3) ◽  
pp. 944 ◽  
Author(s):  
Nicola Alessio ◽  
Anna Lisa Brigida ◽  
Gianfranco Peluso ◽  
Nicola Antonucci ◽  
Umberto Galderisi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Communication ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Molecular Action ◽  
Definition Of ◽  
Inflammatory Molecules ◽  
Therapeutic Activities

Neurodevelopmental lifelong pathologies defined by problems with social interaction, communication capacity and presence of repetitive/stereotyped clusters of behavior and interests are grouped under the definition of autism spectrum disorder (ASD). ASD prevalence is still increasing, indicating the need to identify specific biomarkers and novel pharmacotherapies. Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD, offering the possibility of treating these disorders by stem cell therapy. Indeed, cellular strategies have been postulated, proposed and applied to ASD. However, less is known about the molecular action mechanisms of stem cells. As a possibility, the positive and restorative effects mediated by stem cells could be due to their paracrine activity, by which stem cells produce and release several ameliorative and anti-inflammatory molecules. Among the secreted complex tools, exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication. Exosomes could be the mediators of many stem cell-associated therapeutic activities. This review article describes the potential role of exosomes in alleviating ASD symptoms.

scholarly journals Stem cell therapies and benefaction of somatic cell nuclear transfer cloning in COVID-19 era

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Birbal Singh ◽  
Gorakh Mal ◽  
Vinod Verma ◽  
Ruchi Tiwari ◽  
Muhammad Imran Khan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Drug Testing ◽  
Human Interaction ◽  
Patient Specific ◽  
Wide Range

Abstract Background The global health emergency of COVID-19 has necessitated the development of multiple therapeutic modalities including vaccinations, antivirals, anti-inflammatory, and cytoimmunotherapies, etc. COVID-19 patients suffer from damage to various organs and vascular structures, so they present multiple health crises. Mesenchymal stem cells (MSCs) are of interest to treat acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. Main body Stem cell-based therapies have been verified for prospective benefits in copious preclinical and clinical studies. MSCs confer potential benefits to develop various cell types and organoids for studying virus-human interaction, drug testing, regenerative medicine, and immunomodulatory effects in COVID-19 patients. Apart from paving the ways to augment stem cell research and therapies, somatic cell nuclear transfer (SCNT) holds unique ability for a wide range of health applications such as patient-specific or isogenic cells for regenerative medicine and breeding transgenic animals for biomedical applications. Being a potent cell genome-reprogramming tool, the SCNT has increased prominence of recombinant therapeutics and cellular medicine in the current era of COVID-19. As SCNT is used to generate patient-specific stem cells, it avoids dependence on embryos to obtain stem cells. Conclusions The nuclear transfer cloning, being an ideal tool to generate cloned embryos, and the embryonic stem cells will boost drug testing and cellular medicine in COVID-19.

scholarly journals Wnt5a Signaling in Normal and Cancer Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Zhou ◽  
Thomas J. Kipps ◽  
Suping Zhang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Target Cells ◽  
Dependent Manner ◽  
Self Renewal ◽  
Surface Receptors ◽  
Canonical Wnt

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

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