A preclinical study—systemic evaluation of safety on mesenchymal stem cells derived from human gingiva tissue

Mounting evidence has shown that a novel subset of mesenchymal stem cells(MSCs) derived from human gingiva referred to as gingival mesenchymal stem cells(GMSCs) displays a greater immunotherapeutic potential and regenerative repair expression than MSCs obtained from other tissues. However, the safety of the use of transplanted GMSCs in humans remains unclear. In this study, we evaluated the safety of GMSCs transplanted into mouse, rat, rabbit, beagledog, and monkey as well as two animal modelsof autoimmune diseases. In short- and long-term toxicity tests, infused GMSCs had no remarkable adverse effects on hematologic and biochemical indexes, particularly on the major organs such as heart, liver, spleen, and kidney in recipient animals. It was also shown that GMSCs were well tolerated in other assays including hemolysis, vascular, and muscular stimulation, as well as systemic anaphylaxis and passive skin Arthus reactionin animal models. GSMC infusion did not cause any notable side effects on animal modelsof either autoimmune arthritisor lupus. Significantly, GMSCs most likely play no role in genotoxicity and tumorigenesis. The biological features remained stable for an extended period after cell transfer. GMSCs are safe in various animal modelsof autoimmunity, even during active disease episodes, especially in monkeys. This study paves a solid road for future clinical trials of GMSCs in patients with autoimmune and inflammatory diseases.