Abstract
There is substantial evidence to support the hypothesis that stem cells exert a regenerative effect on damaged tissues/organs by paracrine mechanisms. Stem cells may favor self-tissue/organ repair by means of soluble factor production as well as by release of small vesicles into the extracellular space. Since microvesicles are a heterogeneous population which includes cell surface-shed vesicles and exosomes, herein we call them collectively extracellular vesicles (EVs). EVs enable stem/progenitor cells to transfer information that may change the phenotype of recipient cells. EVs contain selected patterns of proteins, messenger ribonucleic acid (mRNA), long noncoding RNA, and microRNA (miRNA) characteristic of stem/progenitor cells. The transfer of these functional transcripts to injured cells changes their phenotype and activates self-regenerative programs. In this chapter, we discuss studies indicating that EVs derived from different stem cell sources retain the biological activity of stem cells and can mimic their therapeutic effects.
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Conclusions
Conclusions
Taken together, these studies suggest that EVs derived from different stem cell sources retain the biological activity of stem cells and can mimic the therapeutic effects of the cell of origin. However, it is evident that an EV-based therapy does not replace the injured tissue, but may rather coordinate tissue self-repair and limit the injury. By exploiting membrane receptors expressed by the stem cell of origin, EVs were able to home into the site of injury. In addition, EVs have the potential to interfere with multiple cellular pathways involved in different physiological and pathological processes because they contain a complex array of constituents. Identification of the molecular components accountable for the beneficial action of EVs in different pathologies, along with a better understanding of homing processes and of exRNA containment within EVs may prompt new strategies for producing engineered EVs for therapeutic purposes. The use of EVs instead of stem cells may bypass problems such as maldifferentiation and tumorigenesis that can result from the injection of replicating cells into the host organism. Other potential advantages from using EVs include the possibility of extensive expansion in vitro and of cryopreservation and, regarding the stem cell-derived EVs, the absence of immunogenicity. However, before a clinical application can be envisaged, many problems need to be solved. Firstly, the definition of GMP protocols for large-scale EV production and the evaluation of bio-distribution, pharmacokinetics, biosafety, and effectiveness in different pathological conditions.
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Deregibus, M., Iavello, A., Tetta, C., Camussi, G. (2014). Role of Extracellular Vesicles in Tissue/Organ Regeneration. In: Ratajczak, M. (eds) Adult Stem Cell Therapies: Alternatives to Plasticity. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1001-4_13
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