Abstract
The tissue engineering paradigm considers #cells, signals and
scaffolds as the major elements of #tissueengineering approaches to
repair and/or regenerate tissues [1]. Unexpectedly, a paradigm shift
is taking place in this field by the only use of extracellular vesicles
(EVs) to deliver the right signals to the #damagedtissue. In recent
years, EVs role in #intercellularsignalling has begun to emerge [2].
EVs range in size from 30 to 1000 nm and can be derived from the
endosomal system (exosomes, 70-150 nm) or produced by outward
budding of the plasma membrane (#microvesicles, 100-1000 nm)
[3,4]. All EVs are enriched in proteins, #lipids, and #nucleicacids (DNA,
mRNA, miRNA, tRNA) that can be delivered to recipient cells for cellto-
cell communication [5]. In fact, EVs have recently evolved to be
vital components of cell-based therapies based on the observations
that the beneficial effects of cell therapies could not be attributed
to cell survival and differentiation, leading to the thought that cell
therapies act in a #paracrine rather than in a cellular manner [6]. This
shift was based on in vivo data showing that stem cell engraftment
and differentiation at injury sites was very low and transient [7-11].
And on the observation that conditioned media from cultured stem
cells reproduces some of the beneficial effects of intact cells [12,13].
This paracrine effect exerted by stem cells would depend on their
capacity to secrete soluble factors [14], but also, by the release of
EVs [15]. In particular, #preclinicalmodels studying graft versus host
disease, acute kidney failure and ischemic stroke suggest that EVs
exert the stem cells’ #therapeuticeffects [16-18].
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