Abstract
BackgroundMounting 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.MethodsIn 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.ResultsIn 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.ConclusionsGMSCs 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.
Highlights
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
Using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human GMSCs as a GMSC/SIS-ECM tissue graft for the tongue reconstruction and the constructs accelerates wound healing and muscle regeneration and maintains the overall tongue shape [20]. Based upon their known immunomodulatory properties, we have previously reported that adoptive transfer of GMSCs in a mouse model of rheumatoid arthritis significantly reduced the severity of the arthritis and downregulated the production of Th1 and Th17 inflammatory cytokines and enhanced Treg cell differentiation [3]
GMSCs did not induce inflammatory response in vessel or muscle of rabbit, nor did they give rise to hemolysis in vitro The results of the vascular stimulation test showed that there was neither evidence of vascular congestion nor swelling of the surrounding tissues in the GMSCs group, mirroring findings similar to those seen in the control group receiving 0.9% NaCl solution (Fig. 1a)
Summary
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. In 2009, Angeles et al [18] isolated a new population of stem cells from human gingiva, that were referred to as gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities This stem cell subset displayed superior properties of ease of harvesting and expansion in vitro, independency of growth. Huang et al have shown that GMSCs can suppress cell-mediated diseases and were superior to bone marrow mesenchymal stem cells (BMSCs) in inhibiting xenogenic GVHD in humanized animal models [23, 24] These studies suggest that GMSCs may be a promising candidate for cell-based therapy of autoimmune and inflammatory diseases
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