Effect of Adipose-Derived Stem Cells and Their Exo as Adjunctive Therapy to Nonsurgical Periodontal Treatment: A Histologic and Histomorphometric Study in Rats

Abstract

Scaling and root planing (SRP) is of limited value in many cases, so adjunctive treatment was applied to augment its outcome. Adipose-derived stem/stromal cells (ADSCs) were investigated in periodontal regeneration with promising results. However, they have safety concerns. The exosomes (Exo.), which are extracellular vesicles mediating the action of stem/stromal cells, represent a new approach to overcome these concerns. Ligature-induced periodontitis was induced in 50 rats for 14 days, and they were divided into control (5 healthy rats for histologic comparison), SRP group, ADSCs group, and Exo. group, with evaluation intervals at 2 days, and 2 and 4 weeks, including 5 rats in each interval for each group. The specimens were evaluated for histologic description (H&E), histochemical study (Masson trichrome), and histomorphometric study, to evaluate the area % of newly formed tissues. The Exo. group revealed the best results in all intervals with significantly higher area % of newly formed tissues, followed by ADSCs and, finally, SRP. Both Exo. and ADSCs showed organized newly formed tissues with the Exo. group obtaining comparable histologic results to the normal, healthy tissues by 4 weeks. Adipose-derived stem/stromal cells and their Exo. represent a promising adjunctive treatment to SRP.

Emerging functions and clinical applications of exosomes in human oral diseases

“…The followed experiments performed in PDL cells proved that, human MSCs-Exos could be rapidly taken up by PDL cells and promoted the migration and proliferation of PDL cells through CD73mediated adenosine receptor activation of AKT and ERK signaling pathways [25]. Researchers also observed that exosomes secreted by adipose-derived stem cells (ASCs-Exos), exerted a better therapeutic effect on ligatureinduced periodontitis compared to ADSCs themselves, which manifested as a higher area of newly formed tissues [109].…”

A Role for Exosomes in Craniofacial Tissue Engineering and Regeneration

“…Despite advances using exosomes in other fields of medicine, even the most recent general reviews of periodontal tissue regeneration have not considered that MSC exosomes have the potential to direct periodontal regeneration and repair (Chew et al, 2019). Adipose derived stem cell exosomes used to augment non-surgical periodontal therapy in a rat model of ligature-induced periodontitis positively affected periodontium regeneration (Mohammed et al, 2018).…”

Stem cell therapies for periodontal tissue regeneration: a network meta-analysis of preclinical studies

“…Based on the abstract and title reviews, 3810 articles were excluded. After reviewing the full texts of the remaining 202 articles, 60 articles met our eligibility criteria for systematic review and NMA (Supplementary Table 3 shows the references and reasons for exclusion) [15][16][17][18][19][20][21][22][23][24][25].…”

“…The type of defect, especially the number of involved alveolar bone walls, should be considered when choosing the method of cell delivery. When the lesions are retentive, liquid or gel scaffolds can be used without causing the cells to disperse [15,16,25,66]. When the lesions are large, the use of bone substitute can confine the cell-material complex to the surgical site and improve the regeneration process, such as by combining the stem cells and bone substitute or by transplanting the cell sheets attached with polymers to the root surface of the tooth and then filling the bone defects with bone substitute [20,24,61,87].…”

“…Numerous preclinical studies have tested the feasibility, safety, and effectiveness of various stem cell products [13]. Currently, the most studied stem cells, mainly adipose tissue-derived stem cells (ADSCs) [14,15], bone marrow-derived stem cells (BMSCs) [16][17][18], dental pulp-derived stem cells (DPSCs) [19][20][21], gingival-derived stem cells (GMSCs) [22], and periodontal ligament-derived stem cells (PDLS Cs) [23][24][25][26], have been assessed for experimental PTR in a variety of animal models [12]. Stem cells have been exploited for their ability to form multiple periodontal tissues under appropriate induction conditions [27].…”