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and posterior maculae flavae contain stem cells or progenitor cells and these cells
have the capacity to play essential roles in tissue regeneration.
9.14 Vocal Fold Stem Cells and Their Niche in the Human
Newborn Vocal Fold Mucosa
The results of our studies are consistent with the hypothesis that the cells in the
maculae flavae are tissue stem cells or progenitor cells of the human newborn vocal
fold mucosa (Sato et al. 2016b).
Newborns already have maculae flavae at the same sites as in adult vocal folds
(Hirano and Sato 1993 ; Sato and Nakashima 2005 ; Sato and Hirano 1995b). The
newborn maculae flavae are composed of relatively dense masses of cells and situ-
ated at the anterior and posterior ends of the bilateral vocal fold mucosae. The cells
in the newborn maculae flavae possess some features of mesenchymeal cells (Sato
and Nakashima 2005 ; Sato and Hirano 1995b). The cells in the human newborn
maculae flavae possess proteins of all three germ layers (Sato et al. 2016b). They are
undifferentiated cells which arise not from resident interstitial cells but from the
differentiation of bone marrow cells (Sato et al. 2016b).
Extracellular matrices composed of collagen fibers, reticular fibers, elastic fibers
and ground substances are not abundant in the newborn maculae flavae. A new-
born’s macula flava is in the process of acquiring a hyaluronan-rich matrix making
it a candidate for a stem cell niche.
At birth, the cells have already been supplied, likely from the bone marrow, into
the maculae flavae in the newborn vocal fold and are ready to start the growth and
development of the human vocal fold mucosa as a vibrating tissue (Sato and
Hirano 1995b).
9.15 Mechanical Regulation (Cellular Mechanotransduction)
of the Cells in the Human Maculae Flavae
Current scientific findings suggest that the magnitude and frequency of tensile strain
are particularly important in determining the type of mechanically induced differen-
tiation that stem cells will undergo (Kurpinski et al. 2010 ). The macula flava is the
microenvironment where the magnitude and frequency of tensile strain during vocal
fold vibration are greatest (Titze and Hunter 2004 ). The function and fate of the
cells in the human maculae flavae are regulated by various microenvironmental fac-
tors. In addition to chemical factors, mechanical factors also modulate the behavior
of cells in the human maculae flavae.
We hypothesize that the tensions caused by phonation (vocal fold vibration) after
birth stimulate cells in the anterior and posterior maculae flavae to accelerate pro-
duction of extracellular matrices and form the vocal ligament, Reinke’s space and
K. Sato