Abstract
A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other sources of tissues, e.g. bone marrow, adipose or umbilical cord, GMSCs also possess multipotent differentiation capacities and potent immunomodulatory effects on both innate and adaptive immune cells through the secretion of various types of bioactive factors with immunosuppressive and anti-inflammatory functions. Uniquely, GMSCs are highly proliferative and have the propensity to differentiate into neural cell lineages due to the neural crest-origin. These properties have endowed GMSCs with potent regenerative and therapeutic potentials in various preclinical models of human disorders, particularly, some inflammatory and autoimmune diseases, skin diseases, oral and maxillofacial disorders, and peripheral nerve injuries. All types of cells release extracellular vesicles (EVs), including exosomes, that play critical roles in cell-cell communication through their cargos containing a variety of bioactive molecules, such as proteins, nucleic acids, and lipids. Like EVs released by other sources of MSCs, GMSC-derived EVs have been shown to possess similar biological functions and therapeutic effects on several preclinical diseases models as GMSCs, thus representing a promising cell-free platform for regenerative therapy. Taken together, due to the easily accessibility and less morbidity of harvesting gingival tissues as well as the potent immunomodulatory and anti-inflammatory functions, GMSCs represent a unique source of MSCs of a neural crest-origin for potential application in tissue engineering and regenerative therapy.
Highlights
Mesenchymal stromal cells (MSCs) represent a heterogeneous population of postnatal stem cells with self-renewal, multipotent differentiation, and immunomodulatory capabilities (1)
In the last two decades, significant progress has been made in MSCbased tissue engineering (TE) and regenerative therapy across various fields of medicine, including the use of mesenchymal stem cells (MSCs) to treat a large range of human disorders in over 1200 registered and 300 completed clinical trials (5)
Large variations exist in the therapeutic effects and overall clinical outcomes of MSC-based regenerative therapy, which might mainly be attributed to the heterogeneous properties and functions of MSCs that can be produced at different levels, such as donor characteristics, the tissue source, techniques used for cell isolation and expansion, tissue engineering, and product storage/administration (5)
Summary
Mesenchymal stromal cells (MSCs) represent a heterogeneous population of postnatal stem cells with self-renewal, multipotent differentiation, and immunomodulatory capabilities (1). Tongue Defect and Muscle Regeneration A previous study by Ansari et al showed that human GMSCs encapsulated in an injectable 3D RGD-coupled alginate scaffold with multiple growth factors displayed potent myogenic differentiation potentials as evidenced by muscle cell-like morphology with high expression levels of muscle regenerationrelated genes both in vitro and in vivo when encapsulated GMSCs were subcutaneously transplanted into immunocompromised mice. Their results indicated that GMSCs exhibited significantly greater capacity for myogenic regeneration compared to human bone marrow MSCs, suggesting that GMSCs could be a promising candidate source of cells for muscle tissue engineering (123). A study by Gugliandolo A et al showed that hypoxia preconditioning of GMSCs induced the expression of more genes associated with different stages of cortical development, while an increased number of genes associated with development biology and neuronal process were induced in hypoxia-preconditioned GMSCs following
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