scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1959
Author(s):  
Mangesh D. Hade ◽  
Caitlin N. Suire ◽  
Zucai Suo
Keyword(s):  
Regenerative Medicine ◽  
Brain Injuries ◽  
Current Knowledge ◽  
Multivesicular Body ◽  
Cell Types ◽  
Biological Properties ◽  
Cellular Functions ◽  
Surface Receptors ◽  
Differentiation And Proliferation ◽  
Almost All

Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that are then released into the extracellular space through a merging of the multivesicular body with the plasma membrane. These vesicles are secreted by almost all cell types to aid in a vast array of cellular functions, including intercellular communication, cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. This ability to contribute to several distinct processes is due to the complexity of exosomes, as they carry a multitude of signaling moieties, including proteins, lipids, cell surface receptors, enzymes, cytokines, transcription factors, and nucleic acids. The favorable biological properties of exosomes including biocompatibility, stability, low toxicity, and proficient exchange of molecular cargos make exosomes prime candidates for tissue engineering and regenerative medicine. Exploring the functions and molecular payloads of exosomes can facilitate tissue regeneration therapies and provide mechanistic insight into paracrine modulation of cellular activities. In this review, we summarize the current knowledge of exosome biogenesis, composition, and isolation methods. We also discuss emerging healing properties of exosomes and exosomal cargos, such as microRNAs, in brain injuries, cardiovascular disease, and COVID-19 amongst others. Overall, this review highlights the burgeoning roles and potential applications of exosomes in regenerative medicine.

scholarly journals Pharmacology of Adenosine Receptors: The State of the Art

2018 ◽  
Vol 98 (3) ◽  
pp. 1591-1625 ◽  
Author(s):  
Pier Andrea Borea ◽  
Stefania Gessi ◽  
Stefania Merighi ◽  
Fabrizio Vincenzi ◽  
Katia Varani
Keyword(s):  
Adenosine Receptors ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Cell Types ◽  
Structural Features ◽  
Receptor Subtypes ◽  
Cellular Functions ◽  
Novel Drugs ◽  
Rapid Generation ◽  
Almost All

Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A1, A2A, A2B, and A3. Due to the rapid generation of adenosine from cellular metabolism, and the widespread distribution of its receptor subtypes in almost all organs and tissues, this nucleoside induces a multitude of physiopathological effects, regulating central nervous, cardiovascular, peripheral, and immune systems. It is becoming clear that the expression patterns of adenosine receptors vary among cell types, lending weight to the idea that they may be both markers of pathologies and useful targets for novel drugs. This review offers an overview of current knowledge on adenosine receptors, including their characteristic structural features, molecular interactions and cellular functions, as well as their essential roles in pain, cancer, and neurodegenerative, inflammatory, and autoimmune diseases. Finally, we highlight the latest findings on molecules capable of targeting adenosine receptors and report which stage of drug development they have reached.

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals Targeting GRK5 for Treating Chronic Degenerative Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 1920
Author(s):  
Federica Marzano ◽  
Antonio Rapacciuolo ◽  
Nicola Ferrara ◽  
Giuseppe Rengo ◽  
Walter J. Koch ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Cell Types ◽  
Cardiac Cells ◽  
Multifunctional Protein ◽  
Surface Receptors ◽  
Extracellular Signals ◽  
Degenerative Disorders ◽  
Almost All ◽  
Related Proteins ◽  
Different Cell Types

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, called GPCR kinases (GRKs). Given the biological role of GPCRs, it is not surprising that GRKs are also involved in several pathophysiological processes. Particular importance is emerging for GRK5, which is a multifunctional protein, expressed in different cell types, and it has been found located in single or multiple subcellular compartments. For instance, when anchored to the plasma membrane, GRK5 exerts its canonical function, regulating GPCRs. However, under certain conditions (e.g., pro-hypertrophic stimuli), GRK5 translocates to the nucleus of cells where it can interact with non-GPCR-related proteins as well as DNA itself to promote “non-canonical” signaling, including gene transcription. Importantly, due to these actions, several studies have demonstrated that GRK5 has a pivotal role in the pathogenesis of chronic-degenerative disorders. This is true in the cardiac cells, tumor cells, and neurons. For this reason, in this review article, we will inform the readers of the most recent evidence that supports the importance of targeting GRK5 to prevent the development or progression of cancer, cardiovascular, and neurological diseases.

Tubulin heterogeneity regulates functions and dynamics of microtubules and plays a role in the development of drug resistance in cancer

2019 ◽  
Vol 476 (9) ◽  
pp. 1359-1376 ◽  
Author(s):  
Shweta Shyam Prassanawar ◽  
Dulal Panda
Keyword(s):  
Current Knowledge ◽  
Cell Types ◽  
Cellular Functions ◽  
Spatial Cues ◽  
Post Translational Modifications ◽  
Tubulin Isotypes ◽  
Development Of Resistance ◽  
Structural And Functional Properties ◽  
Differential Stability ◽  
Different Cell Types

Abstract Microtubules, composed of αβ-tubulin heterodimers, exhibit diverse structural and functional properties in different cell types. The diversity in the microtubule structure originates from tubulin heterogeneities, namely tubulin isotypes and their post-translational modifications (PTMs). These heterogeneities confer differential stability to microtubules and provide spatial cues for the functioning of the cell. Furthermore, the altered expressions of tubulin isotypes and PTMs are prominent factors for the development of resistance against some cancer drugs. In this review, we summarize our current knowledge of the tubulin isotypes and PTMs and how, together, they control the cellular functions of the microtubules. We also describe how cancer cells use this tubulin heterogeneity to acquire resistance against clinical agents and discuss existing attempts to counter the developed resistance.

scholarly journals Urinary Exosomes

2009 ◽  
Vol 9 ◽  
pp. 1107-1118 ◽  
Author(s):  
Irena Dimov ◽  
Ljubinka Jankovic Velickovic ◽  
Vladisav Stefanovic
Keyword(s):  
Large Scale ◽  
Multivesicular Body ◽  
Cell Types ◽  
Response To Therapy ◽  
Tissue Samples ◽  
Disease Evolution ◽  
Urinary Exosomes ◽  
Cellular Source ◽  
Almost All

Exosomes are nanovesicles of endocytic origin that are secreted into the extracellular space or body fluids when a multivesicular body (MVB) fuses with the cell membrane. Interest in exosomes intensified after their description in antigen-presenting cells and the observation that they can significantly moderate immune responsesin vivo. In the past few years, several groups have reported on the secretion of exosomes by almost all cell types in an organism. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins, reflecting their cellular source. Major research efforts were put into their surprisingly various biological functions and in translating knowledge into clinical practice. Urine provides an exciting noninvasive alternative to blood or tissue samples as a potential source of disease biomarkers. Urinary exosomes (UE) became the subject of serious studies just a few years ago. A recent large-scale proteomics-based study of normal UE revealed a myriad of proteins, including disease-related gene products. Thus, UE have valuable potential as a source of biomarkers for early detection of various types of diseases, monitoring the disease evolution and/or response to therapy. As a relatively new field of research, it still faces many challenges, but UE have already shown some straightforward potential.

scholarly journals Apocarotenoids: Emerging Roles in Mammals

2018 ◽  
Vol 38 (1) ◽  
pp. 153-172 ◽  
Author(s):  
Earl H. Harrison ◽  
Loredana Quadro
Keyword(s):  
Vitamin A ◽  
Current Knowledge ◽  
Biological Activities ◽  
Biological Properties ◽  
Provitamin A ◽  
Plant Origin ◽  
Cellular Functions ◽  
Provitamin A Carotenoids ◽  
Β Carotene ◽  
Biological Actions

Apocarotenoids are cleavage products of C40 isoprenoid pigments, named carotenoids, synthesized exclusively by plants and microorganisms. The colors of flowers and fruits and the photosynthetic process are examples of the biological properties conferred by carotenoids to these organisms. Mammals do not synthesize carotenoids but obtain them from foods of plant origin. Apocarotenoids are generated upon enzymatic and nonenzymatic cleavage of the parent compounds both in plants and in the tissues of mammals that have ingested carotenoid-containing foods. The best-characterized apocarotenoids are retinoids (vitamin A and its derivatives), generated upon central oxidative cleavage of provitamin A carotenoids, mainly β-carotene. In addition to the well-known biological actions of vitamin A, it is becoming apparent that nonretinoid apocarotenoids also have the potential to regulate a broad spectrum of critical cellular functions, thus influencing mammalian health. This review discusses the current knowledge about the generation and biological activities of nonretinoid apocarotenoids in mammals.

scholarly journals Role of Septins in Endothelial Cells and Platelets

2021 ◽  
Vol 9 ◽  
Author(s):  
Katharina Neubauer ◽  
Barbara Zieger
Keyword(s):  
Endothelial Cells ◽  
Higher Plants ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Junctions ◽  
Specific Expression ◽  
Cellular Processes ◽  
Almost All

Septins are conserved cytoskeletal GTP-binding proteins identified in almost all eukaryotes except higher plants. Mammalian septins comprise 13 family members with either ubiquitous or organ- and tissue-specific expression patterns. They form filamentous oligomers and complexes with other proteins to serve as diffusions barrier and/or multi-molecular scaffolds to function in a physiologically regulated manner. Diverse septins are highly expressed in endothelial cells and platelets, which play an important role in hemostasis, a process to prevent blood loss after vascular injury. Endothelial septins are involved in cellular processes such as exocytosis and in processes concerning organismal level, like angiogenesis. Septins are additionally found in endothelial cell-cell junctions where their presence is required to maintain the integrity of the barrier function of vascular endothelial monolayers. In platelets, septins are important for activation, degranulation, adhesion, and aggregation. They have been identified as mediators of distinct platelet functions and being essential in primary and secondary hemostatic processes. Septin-knockout mouse studies show the relevance of septins in several aspects of hemostasis. This is in line with reports that dysregulation of septins is clinically relevant in human bleeding disorders. The precise function of septins in the biology of endothelial cells and platelets remains poorly understood. The following mini-review highlights the current knowledge about the role of septin cytoskeleton in regulating critical functions in these two cell types.

scholarly journals Dictyostelium: A Model for Studying the Extracellular Vesicle Messengers Involved in Human Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 225 ◽  
Author(s):  
Irène Tatischeff
Keyword(s):  
Intercellular Communication ◽  
Current Knowledge ◽  
Cell Model ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Eukaryotic Cell ◽  
Research Field ◽  
Cell Physiology ◽  
Health And Disease ◽  
Almost All

Cell-derived extracellular vesicles (EVs) are newly uncovered messengers for intercellular communication. They are released by almost all cell types in the three kingdoms, Archeabacteria, Bacteria and Eukaryotes. They are known to mediate important biological functions and to be increasingly involved in cell physiology and in many human diseases, especially in oncology. The aim of this review is to recapitulate the current knowledge about EVs and to summarize our pioneering work about Dictyostelium discoideum EVs. However, many challenges remain unsolved in the EV research field, before any EV application for theranostics (diagnosis, prognosis, and therapy) of human cancers, can be efficiently implemented in the clinics. Dictyostelium might be an outstanding eukaryotic cell model for deciphering the utmost challenging problem of EV heterogeneity, and for unraveling the still mostly unknown mechanisms of their specific functions as mediators of intercellular communication.

scholarly journals The Potential Therapeutic Role of Mesenchymal Stem Cells-Derived Exosomes in Osteoradionecrosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yuetian Li ◽  
Xinyue Wang ◽  
Yu Pang ◽  
Shuangcheng Wang ◽  
Meng Luo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Current Knowledge ◽  
Lipid Vesicles ◽  
Cell Types ◽  
Bone Lesions ◽  
Potential Therapeutic Role ◽  
Almost All

As one of the most serious complications of radiotherapy, osteoradionecrosis (ORN) seriously affects the quality of life of patients and even leads to death. Vascular injury and immune disorders are the main causes of bone lesions. The traditional conservative treatment of ORN has a low cure rate and high recurrent. Exosomes are a type of extracellular bilayer lipid vesicles secreted by almost all cell types. It contains cytokines, proteins, mRNA, miRNA, and other bioactive cargos, which contribute to several distinct processes. The favorable biological functions of mesenchymal stem cells-derived exosomes (MSC exosomes) include angiogenesis, immunomodulation, bone regeneration, and ferroptosis regulation. Exploring the characteristic of ORN and MSC exosomes can promote bone regeneration therapies. In this review, we summarized the current knowledge of ORN and MSC exosomes and highlighted the potential application of MSC exosomes in ORN treatment.

scholarly journals ATX expression from GFAP+ cells is essential for embryonic development

2020 ◽  
Author(s):  
Ioanna Sevastou ◽  
Ioanna Ninou ◽  
Vassilis Aidinis
Keyword(s):  
Embryonic Development ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Cellular Functions ◽  
Autoimmune Encephalomyelitis ◽  
Health And Disease ◽  
Genetic Deletion ◽  
Almost All ◽  
G Protein Coupled ◽  
Experimental Autoimmune

AbstractAutotaxin (ATX) is secreted by various type of cells in health and disease and catalyzes the extracellular production of lysophosphatidic acid (LPA). In turn, LPA is a bioactive lysophospholipid promoting a wide array of cellular functions through its multiple G-protein coupled receptors, differentially expressed in almost all cell types. ATX expression has been shown necessary for embryonic development and has been suggested to participate in the pathogenesis of different chronic inflammatory diseases and cancer. Deregulated ATX and LPA levels have been reported in multiple sclerosis (MS) and its experimental model, experimental autoimmune encephalomyelitis (EAE). ATX genetic deletion from macrophages and microglia (CD11b+ cells) attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in MS/EAE. In this report, increased ATX staining was localized to glial fibrillary acidic protein positive (GFAP+) cells, mostly astrocytes, in spinal cord sections from EAE mice at the peak of the disease. However, genetic deletion of ATX from GFAP+ cells resulted in embryonic lethality, suggesting a major role for ΑΤΧ expression from GFAP+ cells in embryonic development, that urges further dissection. Moreover, the re-expression of ATX from GFAP+ cells during the pathogenesis of EAE, reinforces the concept that ATX/LPA is a developmental program aberrantly reactivated upon chronic inflammation.

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