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The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses statement guidelines. Twenty\u2010two studies met the inclusion criteria. Periodontal defects were surgically created in all studies. In seven studies, periodontal inflammation was experimentally induced following surgical defect creation. Differences in defect morphology were identified among the studies. Autogenous, alogenous and xenogenous MSC were used to promote periodontal regeneration. These included bone marrow\u2010derived MSC, periodontal ligament (PDL)\u2010derived MSC, dental pulp\u2010derived MSC, gingival margin\u2010derived MSC, foreskin\u2010derived induced pluripotent stem cells, adipose tissue\u2010derived MSC, cementum\u2010derived MSC, periapical follicular MSC and alveolar periosteal cells. Meta\u2010analysis was not possible due to heterogeneities in study designs. In most of the studies, local MSC implantation was not associated with adverse effects. The use of bone marrow\u2010derived MSC for periodontal regeneration yielded conflicting results. In contrast, PDL\u2010MSC consistently promoted increased PDL and cementum regeneration. Finally, the adjunct use of MSC improved the regenerative outcomes of periodontal defects treated with membranes or bone substitutes. Despite the quality level of the existing evidence, the current data indicate that the use of MSC may provide beneficial effects on periodontal regeneration. The various degrees of success of MSC in periodontal regeneration are likely to be related to the use of heterogeneous cells. 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