Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in regenerative endodontics

Abstract

Regenerative endodontic procedures are an alternative to conventional root-canal treatment and apexification. There are two different tissue engineering approaches that are currently followed, both aiming at the colonisation of the cleaned pulp space by pluripotent cells and subsequent pulp regeneration. Firstly, the transplantation of mesenchymal stem cells (MSCs), and secondly a cell-free strategy that relies on bioactive molecules to trigger the recruitment of the patient’s own cells. The first approach is hampered by costs and regulatory issues. Despite great initial enthusiasm with a clinically used cell-free approach that relies on induced bleeding into the pulp space, results have been revealed to be rather unpredictable, and mere repair rather than regeneration of the pulp-dentin complex is what is typically achieved. Moreover, the extent of further root development is variable, and the concept is limited to immature teeth. This article discusses a third possible way of regenerative endodontics that involves the application of MSC-derived exosomes. These are extracellular vesicles that contain proteins, lipids, and nucleic acids, reflecting the secretome of MSCs. Based on the first in vitro and in vivo studies, exosomes appear to be a potent tool to improve pulp regeneration. This narrative review aims to investigate the therapeutic use of human MSCs or dental pulp-derived exosomes in regenerative endodontics. Furthermore, the focus of this review is on targeting important questions that should be investigated in future in-vivo and clinical studies, such as the choice of scaffold material for exosome delivery into the pulp space.

The Application of Pulp Tissue Derived-Exosomes in Pulp Regeneration: A Novel Cell-Homing Approach

“… 2–4 Moreover, the clinical application of stem cells also faces restrictions on acquisition, expansion, transportation, and storage. 5 , 6 Therefore, the exploration of new therapies to promote dental pulp regeneration using cell-homing techniques has become an urgent need.…”

“…Exosomes are a type of extracellular vesicles and can be used in therapeutic applications due to their important roles in intercellular communication. 5 , 6 Exosomes have also been used in oral regenerative medicine, specifically, for pulp regeneration, and the effectiveness of the technique has been proven. Huang et al found that exosomes secreted by osteoblast-induced dental pulp stem cells (DPSCs) could effectively induce DPSC differentiation in vitro, and could regenerate pulp-like tissue with high expression of odontogenic proteins in nude mice.…”

Mesenchymal Stem Cells Based Treatment in Dental Medicine: A Narrative Review

“…To conclude, although when applied, the CB show promising effects (recent studies claim post-treatment formation of a vascularized tissue with a normal physiological response-vital pulp-like tissue), they are relatively complex, expensive, and not yet thoroughly explored [129]. There are also no clear ideal strategies, or AAE/EAO recommended protocols [4,5].…”

“…Following the harvest, exosomes can even be stored or biobanked through the process of dry-freezing, making them more available and more practical for scientific or clinical use [142]. A recent review paper by Ivica et al focuses on possible exosomes applications in dentistry [5]. The authors state that the evidence for exosome use in regenerative dentistry comes from limited in vitro or animal in vivo studies, so there are currently no sufficient data for safe and practical clinical usage.…”

“…There have been attempts to explore regenerative treatments and apply MSCs with the purpose of regenerating the pulp but with limited success. The obstacles faced in such procedures are high treatment costs, bacterial contamination of the internal tooth anatomy, and unpredictability of the treatment [4,5].…”