Extracellular vesicle-based therapeutics for the regeneration of chronic wounds: current knowledge and future perspectives

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

“…In the first stage, hemostasis, platelets form a blood clot to prevent blood loss. Simultaneously, the platelets secrete hormones, cytokines, and chemokines, including tumor growth factor-β (TGF-β), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), to attract inflammatory cells (growth factors important in wound healing are summarized in Table 6) [9,40,[200][201][202][203][204]. Inflammation, the second step of wound healing, begins within 24 h of injury as neutrophils infiltrate the wound and secrete products, such as toll-like receptors (TLRs) and nuclear factor к-lightchain-enhancer of activated B cells (NF-кB), to attract and activate pro-inflammatory (M1) macrophages [9,40,201,202,204].…”

“…Simultaneously, the platelets secrete hormones, cytokines, and chemokines, including tumor growth factor-β (TGF-β), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), to attract inflammatory cells (growth factors important in wound healing are summarized in Table 6) [9,40,[200][201][202][203][204]. Inflammation, the second step of wound healing, begins within 24 h of injury as neutrophils infiltrate the wound and secrete products, such as toll-like receptors (TLRs) and nuclear factor к-lightchain-enhancer of activated B cells (NF-кB), to attract and activate pro-inflammatory (M1) macrophages [9,40,201,202,204]. M1 macrophages phagocytose pathogens, produce an oxidative burst, and remove apoptotic cells before products including signal transducer and activator of transcription 3 (STAT-3) promote the polarization of M1 macrophages into anti-inflammatory M2 macrophages, thus stimulating inflammatory resolution [205][206][207][208].…”

“…One of the promising approaches for this is an exploitation of cellular therapies using MSCs and the possible role of MSC-Exos in wound healing and regeneration [39]. Though studies using MSCs have revealed that both autologous and allogenous MSCs give promising results [263], several studies have demonstrated that the effectiveness and the regenerative capacity of the conditioned media from MSCs is similar or greater than MSCs when applied to chronic wounds [37,[39][40][41]48,264]. As such, it has been found that the MSC-derived secretome, in the form of exosomes, carries soluble factors and metabolites that play an important part during wound healing [40,41,265].…”

“…In addition to their mechanical differentiation properties, MSCs also secrete exosomes and biomolecules including cytokines, chemokines, and growth factors. Though initial reports indicated that MSCs may play a critical role in tissue repair, investigations have shown poor survival and low grafting potential of MSCs in damaged tissue areas, limiting MSC effectiveness in tissue repair [37][38][39][40][41]. Further studies have demonstrated that beneficial effects of MSCs applications in repair are attributable to paracrine signaling, which includes secreted vesicles such as exosomes [42][43][44][45][46].…”

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

“…[ 228 ] Their intravenous administration leads to their rapid elimination from blood circulation; however, it is possible to encapsulate them in other biomaterials such as hydrogels, thus achieving a prolonged retention time, up to even 5 days in the wound. [ 229 ] A human adipose stem cell‐derived extracellular vesicle (hASC‐exos)‐based miRNA delivery strategy was described by Lv et al. [ 230 ] miR‐21‐5p mimics were loaded into hASC‐exos by electroporation to treat diabetic wounds.…”