Abstract
The incidence of bone-related disorders is continuously growing as the aging of the population in developing countries continues to increase. Although therapeutic interventions for bone regeneration exist, their effectiveness is questioned, especially under certain circumstances, such as critical size defects. This gap of curative options has led to the search for new and more effective therapeutic approaches for bone regeneration; among them, the possibility of using extracellular vesicles (EVs) is gaining ground. EVs are secreted, biocompatible, nano-sized vesicles that play a pivotal role as messengers between donor and target cells, mediated by their specific cargo. Evidence shows that bone-relevant cells secrete osteoanabolic EVs, whose functionality can be further improved by several strategies. This, together with the low immunogenicity of EVs and their storage advantages, make them attractive candidates for clinical prospects in bone regeneration. However, before EVs reach clinical translation, a number of concerns should be addressed. Unraveling the EVs’ mode of action in bone regeneration is one of them; the molecular mediators driving their osteoanabolic effects in acceptor cells are now beginning to be uncovered. Increasing the functional and bone targeting abilities of EVs are also matters of intense research. Here, we summarize the cell sources offering osteoanabolic EVs, and the current knowledge about the molecular cargos that mediate bone regeneration. Moreover, we discuss strategies under development to improve the osteoanabolic and bone-targeting potential of EVs.
Highlights
Cell-free approaches based on the secreted products of cells, have been proposed as therapeutic agents since they can achieve similar results to those elicited by cells themselves, overcoming the complexity that involves the administration to patients of a “live” treatment
A recent study found that adipose tissue (AT)-mesenchymal stem cells (MSCs)-extracellular vesicles (EVs) showed the best performance for in vitro and in vivo chondrogenesis and osteogenesis when compared with bone marrow (BM)-MSCsEVs [67]
The authors demonstrated that EVs could be enriched in these miRNAs when overexpressed in parent MSCs, without affecting distinctive features of EVs such as morphology, size, and the expression of surface proteins CD9 and CD63, which are used as EV markers
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Autologous bone supply is limited and the need of additional surgery for bone extraction increases the risk of infections and morbidity Another option is the use of allografts (from a human donor) or xenografts (from large animals like pigs or bovines), which entail some risk of pathogen transmission; more importantly, these bone implants have shown poor bone regeneration abilities [7]. There is an urgent need to discover new, effective therapies to boost bone regeneration to satisfy the growing world population (progressively more aged) affected by bone conditions On this basis, the field of bone tissue engineering has emerged, focused on developing “bone substitutes” that mimic the bone tissue features, usually formed by a 3D scaffold and bone-relevant cell types, which are able to promote osteogenic differentiation in host tissue without any adverse inflammatory response [8]. We discuss the limitations of EVs when intended for bone regeneration and the emerging strategies that are currently under intensive research to counteract these drawbacks, and we obtain educated EVs with enhanced bone regenerative potential
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