Heterogeneity and Hierarchy of Tissue Stem Cells in the Human Vocal Fold Mucosa

There is growing evidence that the cells in the maculae flavae are tissue stem cells and that the maculae flavae are a stem cell niche of the human vocal fold mucosa. The stem cell system of the tissue stem cells of the human adult and newborn vocal fold mucosa, including the heterogeneity and hierarchy of the cells, was re-viewed and summarized. Regarding the heterogeneity, cobblestone-like polygonal cells, vocal fold stellate cell-like cells possessing lipid droplets in the cytoplasm and fibroblast-like spindle cells were intermingled in the maculae flavae under light and electron microscopy, indicating that three phenotypes of cells were present in the human adult and newborn maculae flavae in vivo. Regarding the hierarchy, cobblestone-like polygonal cells are at the top, while fibroblast-like spindle cells are at the bottom of the cellular hierarchy in the stem cell system. Therefore, vocal fold stellate cell-like cells in the human maculae flavae are likely at the second level of the cellular hierarchy. This suggests that the vocal fold stellate cell-like cells are progenitor cells or transiently amplifying cells in the stem cell system of the human vocal fold mucosa. The cells in the maculae flavae of the human adult and newborn vocal fold mucosa have heterogeneity and hierarchy in the stem cell system in vivo.