Chae Yoon Lim, Jae Hyuck Chang, Won Sun Lee, Jeana Kim, and Il Young Park. Gut and Liver 2022;16:645-59. https://doi.org/10.5009/gnl210311

This study investigated the influence of hypoxic culture conditions on human nasal inferior turbinate-derived stem cells (hNTSCs), a subtype of mesenchymal stem cells (MSCs). It aimed to discern how hypoxia affected hNTSC characteristics, proliferation, and differentiation potential compared to hNTSCs cultured under normal oxygen levels. After obtaining hNTSCs from five patients, the samples were divided into hypoxic and normoxic groups. The investigation utilized fluorescence-activated cell sorting (FACS) for surface marker analysis, cell counting kit-8 assays for proliferation assessment, and multiplex immunoassays for cytokine secretion study. Differentiation potential—osteogenic, chondrogenic, and adipogenic—was evaluated via histological examination and gene expression analysis. Results indicated that hNTSCs under hypoxic conditions preserved their characteristic MSC phenotype, as confirmed by FACS analysis demonstrating the absence of hematopoietic markers and presence of MSC markers. Proliferation of hNTSCs remained unaffected by hypoxia. Cytokine expression showed similarity between hypoxic and normoxic groups throughout cultivation. Nevertheless, hypoxic conditions reduced the osteogenic and promoted adipogenic differentiation potential, while chondrogenic differentiation was relatively unchanged. These insights contribute to understanding hNTSC behavior in hypoxic environments, advancing the development of protocols for stem cell therapies and tissue engineering.

Background and Objectives: This study aimed to investigate the influence of a respiratory mucosa-on-a-chip on the respiratory epithelial differentiation potential of human nasal inferior turbinate-derived stem cells (hNTSCs). Materials and Methods: After isolating hNTSCs from five patients, we divided the samples from the patients into the study group with a mucosa-on-a-chip and the control group with conventional differentiation (using conventional differentiation methods). The respiratory epithelial differentiation potential of hNTSCs was analyzed by histology and gene expression. Results: In the quantitative analysis, PCR showed that the hNTSCs expressed the cytokeratin genes (KRT13, 14), transformation-related protein P63 (TP63), and vimentin of basal cells in the airway epithelium at higher levels, but cytokeratin genes (KRT6) at lower levels, in the mucosa-on-a-chip than in conventional differentiation. In the cytokine analysis (GM-CSF, IFNr, IL-1a, IL-1b, IL-4, IL-5, IL-10, IL-12(p70), IL-13, IL-17A, IL-17E/IL-25, RANTES, TNFa, IL-6, and IL-8), the expressions of IFNr, IL-13, RANTES, TNFa, IL-6, and IL-8 were significantly upregulated in the mucosa-on-a-chip than in conventional differentiation. Conclusions: We conclude that the human respiratory mucosa-on-a-chip using human turbinate-derived mesenchymal stem cells allows the respiratory differentiation of hNTSCs and shows the difference in gene and cytokine expression, which could serve as an alternative to conventional differentiation for the production of functionally competent hNTSCs for future clinical applications.

Background and Objectives: Endothelial cells are essential to various therapeutic strategies for cardiovascular diseases. Developing efficient methods to generate large quantities of well-defined endothelial cells could improve cardiovascular treatment. This study explored the impact of lab-on-a-chip technology on the endothelial differentiation potential of mesenchymal stem cells derived from the human inferior nasal turbinate (hNTSCs). Materials and Methods: hNTSCs were isolated from five patients and divided into two groups: an experimental group subjected to lab-on-a-chip technology and a control group following two-dimensional differentiation protocols. The endothelial differentiation capacity of hNTSCs was assessed through histological examination and gene expression analysis. Results: Comparative evaluation of traditional differentiation methods and lab-on-a-chip technology indicated that hNTSCs expressed endothelial cell-specific markers, including CD34, KDR, CDH5, and CD31. Notably, CD31, CD34, and CDH5 exhibited significantly elevated expression levels in the lab-on-a-chip system. Additionally, cytokine analysis showed marked increases in IL-1a and IL-8 expression under lab-on-a-chip conditions compared to standard differentiation techniques. Conclusions: Lab-on-a-chip technology may enhance the differentiation of hNTSCs into endothelial cells with angiogenic potential, highlighting its promise for future cardiovascular regenerative applications.