Emerging biogenesis technologies of extracellular vesicles for tissue regenerative therapeutics

Abstract

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics.

Restoration of olfactory dysfunctions by nanomaterials and stem cells-based therapies: Current status and future perspectives

“…Thus, to enhance stem cell functions against pathophysiological conditions, recent studies on stem cell-based therapy have adopted new technologies such as virus-mediated transduction of stem cells, gene-editing tools, optogenetics, chemogenetics, extracellular vesicles (EVs), and application of nanoparticles. 109 – 111 …”

“…Although here we focused on the delivery of stem cells, their secretome such as extracellular vesicles (EVs), are considered to be of utmost importance as an alternative to stem cells because of their merits over living cells, including delivery to target specific cell types, less immune responses, stabilization in the body, and the ability to contain drugs. 111 , 138 Some of the applications of EVs to dysfunctional tissues such as kidney diseases, cardiovascular diseases, bone defects, fibrosis, stroke, and spinal cord injuries, have shown the therapeutic efficacy of EVs to levels comparable to those treated with conventional stem cell delivery approaches. 111 , 138 – 140 The applications of stem cell-based therapies for the dysfunctional olfactory system are still in infancy; thus, future strategies need to harness the new technologies that progress in scaffold development and EV biogenesis, in order to potentiate the cellular capacity for regenerating the dysfunctional olfactory tissues.…”

“… 111 , 138 Some of the applications of EVs to dysfunctional tissues such as kidney diseases, cardiovascular diseases, bone defects, fibrosis, stroke, and spinal cord injuries, have shown the therapeutic efficacy of EVs to levels comparable to those treated with conventional stem cell delivery approaches. 111 , 138 – 140 The applications of stem cell-based therapies for the dysfunctional olfactory system are still in infancy; thus, future strategies need to harness the new technologies that progress in scaffold development and EV biogenesis, in order to potentiate the cellular capacity for regenerating the dysfunctional olfactory tissues.…”

New paradigms in regenerative engineering: Emerging role of extracellular vesicles paired with instructive biomaterials

“…It is also reasonable to consider biomaterial culture platforms as a method of large-scale EV manufacturing, given our understanding of biomaterial influences on cell phenotype. 3D cultures are also shown to increase EV yield in response to tissue-like organization (Lee et al, 2021;Rocha et al, 2019). Additionally, EVs isolated from highly controlled culture systems may be optimally tuned to educate naïve recipient cells (endogenous or transplanted) in recipient tissue defects, minimizing the requirement of preconditioned cells for transplantation.…”

Well-orchestrated physico-chemical and biological factors for enhanced secretion of osteogenic and angiogenic extracellular vesicles by mesenchymal stem cells in a 3D culture format

“…29 EV-boosted production, payload content, and bioactivity can be influenced by various engineering approaches such as genetic alteration, application of physical/mechanical cues, 3D cultures, and biomolecular and chemical therapy. 30 Although there is evidence that a 3D culture system can increase EV secretion, there are certain drawbacks, particularly for hydrogel-based 3D cultures. For example, retrieval of EVs from a 3D structure with smaller pores is difficult.…”