The expansion of autologous adipose-derived stem cells in vitro for the functional reconstruction of nasal mucosal tissue.

Abstract

BackgroundI t is established that adipose-derived stem cells (ADSCs) produce and secrete cytokines/growth factors that antagonize mucosal injury. However, the exact molecular basis underlying the treatment effects exerted by ADSCs is ill understood, and whether ADSCs cooperate with adipose tissue particles to improve mucosal function in patients with empty nose syndrome (ENS) has not been explored. We investigated the impact of ADSCs on nasal mucosa, the associated mechanisms, and their use in the treatment of patients with ENS.Results The nasal endoscope and mucociliary clearance assessments were significantly improved (P < 0.05) in patients with (n = 28) and without (n = 2) a rudimentary turbinate that received ADSCs combined with fat granules transplantation. Patients experienced a significant improvement in nasal obstruction and nasal mucociliary clearance after nasal turbinate angioplasty (P < 0.05). H&E staining, Masson’s staining, and AB-PAS staining confirmed that inflammation was significantly reduced, collagenous fibers became aligned, fewer deposits were observed, and the mucosal proteins generated from caliciform cells increased following treatment. After a 14-day incubation period, ADSCs developed a polygonal cobblestone shape characteristic of human epithelial cells. Furthermore, immunohistochemical analysis revealed the presence of epithelial markers such as cytokeratin-7, and cytokeratin-19. Western blot analysis showed the presence of specific epithelial cell markers including cytokeratin-7, cytokeratin-14 and cytokeratin-19 in these epithelial like cells (ELC); these markers had low expression levels of ADSCs.ConclusionsThe reconstruction of mucosal function by nasal turbinate angioplasty combined with ADSCs and autologous adipose tissue particle transplantation significantly improved the symptoms of patients with ENS. This is a new procedure that will improve mucosal restoration treatment options in patients with ENS. Furthermore, we undertook preliminary explorations of the underlying mechanisms involved, and found that transplantation of ADSCs could induce epithelial cells to improve mucosa function in patients with ENS in the micro-environment of injection areas.