Comparative Outcomes of Local and Systemic Mesenchymal Stem Cell Therapies on Periodontal Regeneration and Cardiac Health in a Rat Model of Periodontitis

Abstract
Introduction: Periodontitis is a widespread chronic inflammatory condition characterized by the progressive destruction of periodontal tissues, leading to tooth loss and systemic complications, including adverse effects on cardiac function. Despite the well-documented regenerative potential of mesenchymal stem cells (MSCs), the comparative efficacy of local versus systemic administration of adipose-derived MSCs (AD-MSCs) in addressing both periodontal and cardiac dysfunction remains insufficiently studied. This research aimed to investigate the therapeutic impact of AD-MSCs in mitigating periodontitis and its systemic repercussions, with a focus on cardiac health.

Methods: AD-MSCs were isolated and characterized based on their morphology, surface marker expression (CD29, CD90, and CD45), and multi-lineage differentiation potential. A rat model of ligature-induced periodontitis was established to mimic chronic periodontal inflammation. Following the induction of periodontitis, AD-MSCs were either administered locally or systemically. Periodontal regeneration was assessed using clinical and imaging methodologies, while cardiac function was evaluated through echocardiography to measure systolic and diastolic parameters.

Results: The AD-MSCs retained their mesenchymal properties and regenerative capacity throughout the experiment. Local administration significantly enhanced periodontal regeneration, reduced inflammation, and improved systolic cardiac performance, as evidenced by higher ejection fraction and fractional shortening. Histological analysis revealed reduced myocardial fibrosis and better cardiomyocyte alignment in locally treated groups. However, persistent diastolic abnormalities in both treatment groups highlighted the need for extended therapeutic interventions to achieve comprehensive cardiac recovery.

Conclusions: This study demonstrates that the local delivery of AD-MSCs yields superior outcomes in treating periodontal and systemic inflammatory conditions, including improved cardiac function. These findings emphasize the need for tailored stem cell delivery strategies to optimize regenerative therapies for clinical applications.