دانلود کتاب Mesenchymal Stem Cell Derived Exosomes
Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool.
Introduces the MSC-exosome mediated cell-cell communication
Covers the major functional benefits in current MSC-derived exosome studies
Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies
CHAPTER 1 Insights into the Mechanism of Exosome Formation and Secretion
Kobina Essandoh, Guo-Chang Fan Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Contents
Introduction
Signalings in the Regulation of Endocytosis
Signalings in the Regulation of Early Endosome
Signalings in the Regulation of Exosome Cargo Loading to Late Endosomes
Signalings in the Regulation of the Fate of Multivesicular Bodies (MVBS)
Signalings in the Regulation of Exosome Release
Other signalings in the Regulation of Exosome Biogenesis and Release Stress and Pathologic Conditions can Stimulate Exosome Release
Concluding Remarks References
۱INTRODUCTION
Exosomes are naturally generated nanoparticles from cells that range between 30 and 100 nm in size. The initial concept of exosomes can be traced to recticulocytes that secret transferrin receptor-containing tiny double membrane-bound vesicles [1]. Unlike other membrane proteins that are degraded by the endosomal pathway, transferrin receptors were released through exosomes when the reticulocytes matured into erythrocytes [2]. These exosomes were defined as products of the endosomal sorting path
way, as they originated from the intraluminal vesicles (ILVs) located in the lumen of multivesicular bodies (MVBs) [3]. Since then, numerous types of cells such as dendritic cells [4], B cells [5],T cells [6], epithelial cells [7], and mast cells [8] have been observed to release exosomes. Interestingly, exosomes collected from different cell types are rich in endosomal pathway proteins such as tumor susceptibility gene 101 (Tsg101), Alix, tetraspanins (CD9, CD63, CD81), and heat shock proteins (1.e., Hsc70 and Hsp90) [9]
Over the past few years, much of the research in the field of exosomes has centered on their role in cell-to-cell communication [3,10,11] and regulation of pathophysiological conditions such as cancer, liver disease, immune-defective disease, and neurodegenerative diseases [12–۱۵]. In addition, research into stem cell-derived exosomes has focused on therapeutic intervention and tissue repair after injury [16-20]. While the functional role of exosomes has been widely reviewed elsewhere, fewer reviews have sum
marized the processes underlying the formation of exosomes. Therefore, in this chapter, we will discuss the current knowledge on the regulation of the biogenesis and release of exosomes. As products of the endocytic-endosomal pathway, biogenesis of exosomes will be discussed through endocytosis, maturation of early to late endosome, formation of MVBs, and the release of ILVs from the cell.
۲SIGNALINGS IN THE REGULATION OF ENDOCYTOSIS
The endocytic pathway was initially thought of as a mechanism to downregulate plasma membrane receptors such as receptor tyrosine kinase (RTK) and G-protein coupled receptors (GPCRs) [21]. Later studies showed that RTKs or GPCRs might couple to extracellular signal-regulated kinase (ERK)-activating complexes to sustain signals [21,22]. Endocytic vesicles are formed from internalization of cell surface proteins. This process can be clathrin-dependent or -independent
Clathrin-dependent endocytosis involves the formation of clathrincoated pits along the plasma membrane, which causes inward budding of the membrane into intracellular vesicles. The clathrin-dependent pathway has been implicated in the endocytosis of RTKs, GPCRs, and transferrin receptors [23]. The formation of clathrin on the plasma membrane is preceded by the recruitment of an adaptor protein 2 (AP2) adaptor protein,
which specifically binds to lipid phosphatidylinositol-4,5-bisphosphate (Ptdlns (4,5)P2] ata nucleation module on the membrane orat the cytoplasmic side of the receptor [24]. At these modules, there is recruitment of complexcontaining FCH domain only (F-BAR domain-containing Fer/Cip4 homology domain-only, FCHO) proteins, EGFR pathway substrate 15 (EPS15), and intersectins [24-26]
کتاب Mesenchymal Stem Cell Derived Exosomes
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نویسندگان : Yaoliang Tang و Buddhadeb Dawn
تعداد صفحات : ۲۵۶
حجم فایل : ۴ مگابایت
فرمت فایل : پی دی اف