Exosome Biology and Therapeutics

Exosome Biology and Therapeutics

Wood, M. J. A.

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INDICE: Table of Contents: 1) Introduction to exosome biology and therapeutics: WOOD, Oxford An overview of the history of exosome discovery and investigation, putting this into a state of the art perspective that incorporates their roles in development, tissue maintenance and aging, and their potential power as therapeutic agents in regenerative medicine applications 2) Exosome definition and characterisation: e.g. LOTVALL, Gothenburg Exosomes are a unique sub–class of cellular microvesicle. This chapter will outline our current understanding of what exosomes are and how they can be identified and characterised using state of the art scientific methods including transcriptomics and proteomics 3) Exosome biogenesis: e.g. MEISNER, Novartis, Basel One of the unique features of exosome biology and the one that distinguishes exosomes from other cellular microvesicles is their mode of origin or biogenesis. This chapter will describe their biogenesis in details and their origins from intracellular multivesicular bodies. It will review this process and how it is regulated and to what extent the mechanisms for the intracellular packaging of exosome cargoes is known 4) Exosome secretion: e.g. THERY, Paris Exosomes are released in a regulated manner by all cells from multivesicular bodies that reside within the cellular endosomal pathway. This chapter will explore how these vesicles are released, what regulates this process, how it varies from cell to cell and how it might be hijacked or usurped in disease 5) Exosome proteomics: e.g. SIMPSON. Melbourne A major clue to the biological functions of exosomes resides in their protein repertoire and in particular the proteins that are displayed on the exosome vesicle surface. These determine for example how exosomes are capable of migrating within the body and transferring their cargoes to specific cell types. This chapter will review current knowledge on the exosome protein repertoire and to what extent a core of conserved exosome proteins are found within exosomes derived from all cell types 6) Exosomes as transporters of RNA: e.g. LOTVALL, Gothenburg One of the major breakthroughs in our understanding of exosome biology was the discovery that exosome cargo included messenger RNA and small non–coding RNAs known as microRNAs. Moreover these RNAs were found to be capable of being transferred to recipient cells and capable of function within these cells, therefore serving as a new mechanism for the intercellular exchange of genetic information. This chapter will review this fascinating aspect of exosome biology. 7) Exosomes and stem cell plasticity: e.g. QUESENBERRY, Providence A class of cells that are particularly rich in exosome production are stem cells and this highlights the potential importance of exosomes in development of the organism and also in the regeneration and repair of tissues in the adult where stem cell activity is required. This chapter will review the role of exosomes in the field of stem cell turnover and maintenance of tissues. 8) Exosomes and immune regulation: e.g. ASKENASE, Yale One of the areas of biology in which exosomes have been studied in detail is in the regulation of immune responses, where they provide a highly sophisticated local intercellular communication system that serves to drive and determine the outcome of immune activity. This chapter will review the role of exosomes in the regulation of the immune system 9) Exosomes and immune regulation in the brain: e.g. PLUCHINO, Cambridge, UK An area of growing interest is the potential role of exosomes in the regulation of immune activity within the nervous system, where immune responses and the activity of resident immune cells such as astrocytes and microglia are tightly controlled. This chapter will review the role of exosomes in the local regulation of immune activity within the brain and the potential importance of exosomes in dysregulated immune responses within the brain such as occurs in multiple sclerosis 10) Exosomes and pathogenesis of neurodegenerative disease: e.g. ALVAREZ, London A recent area of discovery is the role that exosomes play in intercellular communication within the brain and the potential role of exosomes in the development of neurodegenerative diseases such as Alzheimer?s and Parkinson?s diseases where they have been discovered to transfer abnormal disease proteins from diseased cells to normal cells within the brain, thereby mediating spread of the disease 11) Exosomes and tumour pathogenesis: e.g. SKOG, Amsterdam Another major breakthrough in the field of exosome biology was the discovery that tumour derived exosomes originating from tumours within the brain could be detected within the blood. Not only therefore are exosomes likely to be involved in the pathogenesis of brain and other tumours, possibly being integral to the mechanisms of metastasis but they also may provide a diagnostic window into the type and stage of the tumour if they can be detected in the blood and analysed. Exosomes are therefore one of the leading candidates for tumour biomarkers 12) Exosomes and viral infections: e.g. BAUR, Germany The pathway of exosome biogenesis can be potentially usurped in many cellular disease processes, one of which is viral infection, where viruses are highly likely to hijack the exosome pathway and secretory mechanism to facilitate their spread within the organsism. This chapter will review our current understanding of the role of exosomes in viral pathogenesis and the prospects of inhibiting viral infection by blocking the exosome pathway using small molecule drugs 13) Exosomes as disease biomarkers: e.g. Falcon–Perez, Spain Although originally identified as potential disease biomarkers in cancer, it is now emerging that exosomes and their contents are likely to be abnormal in a range of disease processes and that these can be detected in a range of body fluids including serum, cerebrospinal fluid and urine, providing a novel diagnostic window into a range of medically important diseases 14) Exosomes and the treatment of autoimmune disease: e.g. ROBBINS, Pittsburgh Given their fundamental role in regulating immune responses the idea that exosomes could be utilised to regulate or downregulate immune responses in autoimmune diseases is being explored. This chapter will review the potential of exosomes as immune regulatory agents 15) Exosomes for regenerative cardiac medicine: e.g. LIM, Singapore A further major breakthrough was the recent discovery that many of the potential therapeutic benefits of stem cells in regenerative medicine are mediated via exosomes. In other words the stem cells themselves may not be necessary if the exosomes can be isolated and used for therapeutic ends. This has been especially highlighted in repair of the injured heart which will be reviewed in detail in this chapter. 16) Exosomes and RNAi therapies: e.g. LAKHAL and WOOD, Oxford A major breakthrough in the exosome field was the recent demonstration that exosomes can be developed as sophisticated drug delivery vehicles with the potential to deliver a range of macromolecular drug cargoes such as RNA and antibodies in a targeted fashion to specific cells within the body opening up the nanomedicine field intelligent drug delivery. This will be reviewed in this chapter by Lakhal and Wood who developed the exosome drug delivery nanotechnology 17) Exosomes and applications in biotechnology: e.g. SEOW, Singapore Exosomes with their growing biological importance have many potential roles in areas of biotechnology, from drug delivery, to stem cell regulation, to their use in stem cell reprogramming methods in the laboratory to applications in regenerative medicine and synthetic biology. For many of these technological applications exosome populations will need to be isolated, characterised, scaled up and exploited and this burgeoning field of exosome biotechnology will be reviewed in this chapter

  • ISBN: 978-1-118-33580-2
  • Editorial: Wiley–Blackwell
  • Encuadernacion: Cartoné
  • Páginas: 350
  • Fecha Publicación: 09/05/2014
  • Nº Volúmenes: 1
  • Idioma: Inglés