The Empty Nose Syndrome (ENS) is a rare rhinological disease occurring in 20% of patients undergoing total or subtotal turbinectomy(Chhabra N et al. 2009). A paradoxical sensation of nasal obstruction characterizes ENS despite an open nasal airway. This phenomenonis due to an altered nasal aerodynamic that, combined with the reduction of the mucosal tissue and the loss of sensory, tactile, and thermalreceptors, dramatically alters the nasal physiological functions such as humidification, warming of the inhaled air, and mucociliaryclearance. patients' quality of life (Huang CC et al.2022). There is no cure; only palliative, non-resolutive therapies are available.
The project aims to characterize the trascriptomes of airway epithelial and chondrocytes cells to develop a fully autologous pseudo-turbinate composed of a tissue-engineered nasal-cartilage graft (N-TEC) covered by a completely functional airway epithelium. The N-TECconstruct is already clinically applied to treat other nasal and articular-cartilage defects (Fulco et al., 2014; Mumme et al., 2016). Here,airway epithelial cells previously expanded from a nasal mucosal biopsy will be added to restore respiratory function.
Innovative solutions to regenerate the three-dimensional human turbinate would first focus on molecular characterization and analysis ofpathways that maintain the differentiated chondrocytes and sustain holoclone-forming cells by single-cell RNA profiling of airway epithelia.
Preliminary experiments have shown that holoclone-forming cells of epithelia, namely the stem cells, can activate different transcriptionalprograms, referred to as "holoclone-signature" (Enzo et al 2021). These transcriptional programs were not described for airway epitheliumalone or in association to other cell types, to study the transcriptional modulation within the stem cell compartment. This project will thusgenerate RNA-seq data from single cells obtained directly from human airway epithelial and chondrocyte cultures initiated from at least 3different human airway biopsies.
The identification of pivotal transcription factors will highlight specific pathways and TFs, validated by selected agonist/antagonists, siRNAor other techniques to stimulate proliferation or differentiation of cells in the human turbinate-like construct and optimize the human nasaltissue engineering conditions.
The characterization and development of the components will highlight the cell requirements in the complex reconstruction of multicellularstructures as the nasal turbinate airways and will pave the way for other life-threatening respiratory diseases.