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

Abstract

Background 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. Methods In this study, we evaluated the safety of GMSCs transplanted into mouse, rat, rabbit, beagle dog, and monkey as well as two animal models of autoimmune diseases. Results 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 reaction in animal models. GSMC infusion did not cause any notable side effects on animal models of either autoimmune arthritis or lupus. Significantly, GMSCs most likely play no role in genotoxicity and tumorigenesis. The biological features remained stable for an extended period after cell transfer. Conclusions GMSCs are safe in various animal models of 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. Electronic supplementary material The online version of this article (10.1186/s13287-019-1262-5) contains supplementary material, which is available to authorized users.

B7-H1 Promotes the Functional Effect of Human Gingiva-Derived Mesenchymal Stem Cells on Collagen-Induced Arthritis Murine Model

“…17 Our recent pre-clinical safety studies in mice and monkey further documented safety of these cells for clinical application for future use in the human. 42 Due to the low immunogenicity of MSCs, it has been demonstrated that GMSCs can be successfully grafted in mouse and humanized animal models. 4,19,21 Here, we chose PDFs as control cells, because they share the similar appearance and many phenotypic features with GMSCs but they own lower immunoregulatory and regeneration abilities.…”

Gingiva-Derived Mesenchymal Stem Cells: Potential Application in Tissue Engineering and Regenerative Medicine - A Comprehensive Review

“…In addition, following transplantation of human GMSCs into mouse, rat, rabbit, beagle dog, and monkey as well as in GMSC-treated animal models of autoimmune arthritis or lupus, GMSCs were well tolerated by all recipient hosts without any obvious systemic adverse effects, e.g. toxicity, abnormal immune reactions, and tumorigenesis, thus having further demonstrated the safety of GMSC transplantation and paved the way for clinical studies of GMSCs in regenerative therapy (168). Up to date, there are only two registered clinical trials on the use of GMSCs in the treatment of periodontitis (NCT03137979 and NCT03638154), but the current status and outcomes are not clear (https://www.…”

Overview of Mucoadhesive Biopolymers for Buccal Drug Delivery Systems

“…The buccal lining is also one of the robust lining of human body and can be used for systemic drug delivery [56]. As compared to other oral linings like sublingual route (floor of the mouth) [57], gingival route (gums) [58], linings around the lips, palatal mucosal route etc. [59], The buccal lining have different permeability to selective drugs, different anatomy, and desired length in order to keep the hold on the drug delivery dosage form like patches, tablets, semi-solid dosage form [60].…”