Exosomes Derived from Stem Cells from the Apical Papilla Promote Dentine-Pulp Complex Regeneration by Inducing Specific Dentinogenesis

Abstract

Regenerative endodontic procedures (REPs) are a new option for the treatment of dental pulp or periapical diseases in permanent teeth with open apices. Histologically, the new tissues formed in the root canal after REPs are mainly cementum- or bone-like mineralised tissues, but not the real dentine-pulp complex. Therefore, how to promote dentine-pulp complex regeneration and improve the clinical effects of REPs has become a prominent research topic. Stem cells from apical papilla (SCAP) are derived from the dental papilla that can differentiate into primary odontoblasts and dental pulp cells that produce root dentine and dental pulp. Exosomes are the key regulator for the paracrine activity of stem cells and can influence the function of recipient cells. In this study, SCAP-derived exosomes (SCAP-Exo) were introduced into the root fragment containing bone marrow mesenchymal stem cells (BMMSCs) and transplanted subcutaneously into immunodeficient mice. We observed that dental pulp-like tissues were present and the newly formed dentine was deposited onto the existing dentine in the root canal. Afterwards, the effects of SCAP-Exo on the dentinogenesis of BMMSCs were elucidated in vitro. We found that the gene and protein expression of dentine sialophosphoprotein and mineralised nodule formation in BMMSCs treated with SCAP-Exo were significantly increased. In summary, SCAP-Exo were endocytosed by BMMSCs and obviously improved their specific dentinogenesis. The use of exosomes derived from dental stem cells could comprise a potential therapeutic approach for dentine-pulp complex regeneration in REPs.

Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration

“…Zhuang and colleagues showed similar results, with SCAP-derived exosomes increasing the osteogenic potential of BM-MSCs in vitro and in vivo [88]. In Vitro, their results showed that increasing concentrations of exosomes effectively increased mineralization and DSPP expression in BM-MSCs [88].…”

“…From 15 publications analyzed, CD105 was described to be expressed on SHED in 14 publications, while CD73 and CD90 were described to be expressed in 9 and 10 publications [58,[66][67][68][69][70][71][72][73][74][75][76][77][78][79]. The analysis of marker expression on SCAP was as follows: 15 publications were analyzed, and the most described markers expressed were CD146 (13), CD73 (8), CD90 (8), and CD105 (8) [27,66,[80][81][82][83][84][85][86][87][88][89][90][91][92]. SCAP is the dental stem cell type where CD146 is described as the most prominent positive marker.…”

The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes

“…Functionally, exosomes derived from SCAP were able to promote BMMSC-based dentine-pulp complex regeneration when implanted subcutaneously into immunodeficient mice together with tooth fragments, BMMSCs, and scaffold. Moreover, exosomes derived from SCAP promoted the specific dentinogenesis of BMMSCs [140]. Exosomes also displayed anti-apoptotic activity in odontoblasts.…”

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

“…Moreover, in the same study, it was reported that stem cell proliferation was strongly affected by exosomes. Differentiation towards odontoblasts was also detected in BMMSCs after they were endocytosed (Zhuang et al, 2020).…”