Mesenchymal stem cell‐derived small extracellular vesicles as cell‐free therapy: Perspectives in periodontal regeneration

Abstract

Mesenchymal stem cells (MSC) are involved in the regeneration of the different missing or compromised periodontal tissues. MSC‐derived small extracellular vesicles (sEV) have recently been explored as a favorable substitution for stem cell therapy, as they are capable of producing therapeutic effects comparable to those of their parent cells, with advantages over cell therapy. The aim of this review is to evaluate the use of mesenchymal stem cells (MSC)‐derived sEV as cell‐free therapy in periodontal regeneration. A review of the scientific literature on sEV and their use in periodontal regeneration was performed. The main characteristics of sEV are described, and their mechanisms of action and potential biological effects in periodontal regeneration are studied. A summary of existing preclinical studies conducted in animals is performed. The results indicate that sEV derived from MSC are emerging as a promising new therapeutic tool in the field of periodontal regeneration and may become an ideal therapeutic option. In this review, we have summarized recent advances in this regard in order to better understand this newly emerging treatment. First results in vivo are promising and show a favorable potential for cell‐free therapy in periodontal regeneration.

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium

“…In fact, multiple researchers have found that exosomes released from MSCs from different sources can differentially alleviate periodontitis and promote periodontal regeneration. 17 Among all sources of MSCs, dental pulp stem cells (DPSCs) have attracted particular attention because relative to BMSCs, they are readily accessible, less tumorigenic and demonstrate increased osteogenic and proliferative activity, showing greater capacity for the treatment of periodontitis. 18 – 20 In this context, we have conducted a number of studies to expand the understanding of DPSCs and facilitate their clinical application.…”

Matrix vesicles from dental follicle cells improve alveolar bone regeneration via activation of the PLC/PKC/MAPK pathway

“…In this regard, the well-repair of alveolar bone loss caused by periodontal diseases or other pathological stimuli is of great significance to ensure the structural integrity and functional coordination of periodontal tissues [ 51 ]. To date, there is still an unmet need for novel cell-free regenerative therapies, which are expected to bring favorable prognoses and avoid the problems associated with the direct administration of stem cells [ 14 , 17 ]. This study demonstrated that DFC-derived CRMVs significantly strengthened alveolar bone regeneration and achieved a comparative therapeutic level of MSCs-based treatment in a murine periodontal defect model.…”

“…The conventional therapies, including guided tissue regeneration (GTR), autologous bone grafting and heterogeneous bone filling, have obtained some successful cases, but commonly showed limited efficacy, prolonged therapeutic period and even secondary injuries in some complex conditions [ 7 – 9 ]. Additionally, mesenchymal stem cells (MSCs)-based therapies exhibited curative effects [ 10 ], while the associated inflammatory responses and safety issues seem inevitable [ 11 – 14 ].…”

“…It is indicated the efficacy of MSCs relies on the paracrine course and the induction of extracellular vesicles (EVs) [ 15 , 16 ]. Recently, the EVs-based treatment has been proposed as a feasible cell-free therapy to manage these clinical scenarios, with the goal of regenerating lost or damaged tissues to restore normal function and structure [ 14 , 15 , 17 ]. EVs are a group of cell-released particles, which contain plenty of biocompatible cargos including lipids, protein, and nucleic acid, and induce the activities in intracellular communication [ 17 ].…”

Periodontal and Dental Pulp Cell-Derived Small Extracellular Vesicles: A Review of the Current Status

“…On the other hand, a cell-free approach, centered around cell products (i.e., EVs derived from these cells), has been proposed, and there is an emerging focus on cell-derived EVs as potential therapeutic agents to promote periodontal regeneration. The utilization of sEVs for dental tissue regeneration is emerging as a viable cell-free treatment option, with ‘proof of concept’ studies reported using bone marrow or adipose MSC-derived sEVs (reviewed in [ 41 , 42 , 43 ]); yet, periodontal or dental pulp cell sources are likely to uniquely reflect the functional complexity of the periodontium and oral cavity.…”