Microenvironment Can Induce Development of Auditory Progenitor Cells from Human Gingival Mesenchymal Stem Cells

Abstract

Sensorineural hearing loss in mammals occurs due to irreversible damage to the sensory epithelia of the inner ear and has very limited treatment options. The ability to regenerate the auditory progenitor cells is a promising approach for the treatment of sensorineural hearing loss; therefore, finding an appropriate and easily accessible stem cell source for restoring the sense of hearing would be of great interest. Here, we proposed a novel easy-to-access source of cells with the ability to recover auditory progenitor cells. In this study, gingival mesenchymal stem cells (GMSCs) were utilized, as these cells have high self-renewal and multipotent differentiation capacity and can be obtained easily from the oral cavity or discarded tissue samples at dental clinics. To manipulate the biophysical properties of the cellular microenvironment for promoting GMSC differentiation toward the target cells, we also tried to propose a candidate biomaterial. GMSCs in combination with an appropriate scaffold material can, therefore, present advantageous therapeutic options for a number of conditions. Here, we report the potential of GMSCs to differentiate into auditory progenitor cells while supporting them with an optimized three-dimensional scaffold and certain growth factors. A hybrid hydrogel scaffold based on peptide modified alginate and Matrigel was used here in addition to the presence of fibroblast growth factor-basic (bFGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF). Our in vitro and in vivo studies confirmed the auditory differentiation potential of GMSCs within the engineered microenvironment.

Whitlockite-Enabled Hydrogel for Craniofacial Bone Regeneration

“…We confirmed the stemness of the isolated GMSCs, as previously described, by studying the expression of negative MSC markers, namely, human CD34 and CD45, and positive MSC markers, namely, CD76, CD106, and CD146 (BD Biosciences, Franklin Lakes, NJ), using flow cytometry . Previously, we showed the expression of stemness surface markers of harvested human GMSCs and their multilineage differentiation capacity after passages 4–6 in vitro and in vivo . , All the cells were subcultured up to passage four before entering the studies. Evaluation of stemness markers demonstrates that GMSCs maintain their stemness even up to passage six (Figure S2d).…”

“…15 Previously, we showed the expression of stemness surface markers of harvested human GMSCs and their multilineage differentiation capacity after passages 4−6 in vitro and in vivo. 15,78 All the cells were subcultured up to passage four before entering the studies. Evaluation of stemness markers demonstrates that GMSCs maintain their stemness even up to passage six (Figure S2d).…”

Harnessing Dental Stem Cell Immunoregulation Using Cell-Laden Biomaterials

“…Studies have shown that environmental signaling from mechanical forces, biological stimuli, and physical material properties can affect various cellular behaviors, including spreading, assembly of focal adhesions and actin stress fiber formation, and differentiation (Bissell et al 1982; Pouraghaei et al 2020). It has been shown that matrix stiffness controls the immunoregulatory potential of MSCs by changing the cell morphology and cytoskeletal polymerization in a way that decreasing the matrix stiffness enhances the expression of immunosuppressive genes such as COX-2, TSG-6, and IDO (Ji et al 2019).…”

“…Gingival MSCs are easily accessible from healthy or inflamed gingiva and are readily found in discarded dental tissue samples (Ge et al 2012). These neural crest–derived cells are capable of forming various tissues, such as bone and sensory components of the nervous system (Yamada et al 2011; Pouraghaei et al 2020).…”

A narrative overview of utilizing biomaterials to recapitulate the salient regenerative features of dental-derived mesenchymal stem cells

“… 83 In this context, GMSCs, as an easily accessible source of MSCs, have shown promising outcomes in developing auditory progenitor cells when encapsulated within a biomimetic 3D hydrogel and given the necessary growth factor cocktail. 84 …”