181the maculae flavae are a candidate for a stem cell niche, which is a microenviron-
ment nurturing a pool of tissue stem cells (Sato et al. 2012b).
9.12 Origin of Cells in the Human Maculae Flavae
Bone marrow-derived cells have received a great deal of attention with regard to
tissue development and regeneration. Bone marrow-derived cells are considered to
contain bone marrow derived mesenchymal stem cells, which are multipotent cells
capable of self-renewal (Pittenger et al. 1999 ; Prockop 1997 ), and to be the origin
of circulating fibrocytes, which are associated with wound healing and tissue fibro-
sis (Bucala et al. 1994 ). They circulate in the peripheral blood and are distributed to
organs under normal conditions. When tissue is injured, they contribute to tissue
repair by cell differentiation and migrate into injured tissue as needed (Forbes et al.
2004 ; Brittan et al. 2002 ).
The cells in the human maculae flavae express CD34 (hematopoietic stem cell
marker). They also express CD45 (leukocyte common antigen), and collagen type I
(Kurita et al. 2015 ). These proteins (CD34, CD45 and collagen type I), which are
major makers of bone marrow derived circulating fibrocytes, are present in the cells
in the human maculae flavae (Kurita et al. 2015 ).
Circulating fibrocytes were first described as blood-born fibroblast-like cells by
Bucala, et al. (Bucala et al. 1994 ) They were found to be unique cells because they
co-expressed hematopoietic markers as well as collagen type I and other
mesenchymal markers. CD34, CD45 and collagen type I are major markers for
circulating fibrocytes derived from bone marrow (Abedi 2012 ). CD34, CD45 and
collagen type I are expressed in the cells in the human adult maculae flavae.
Consequently, cells in the human maculae flavae quite possibly arise, not from resi-
dent interstitial cells of the vocal fold mucosa, but from the differentiation of bone
marrow cells via peripheral circulation (Kurita et al. 2015 ).
9.13 Side Population Cells in the Vocal Fold Mucosa
Side population cells are regarded as a cell population enriched with stem cells or
progenitor cells, and recognized as a candidate for tissue stem cells.
In one recent study, side population cells were identified in the epithelium and
subepithelial tissue including the anterior and posterior maculae flavae (Yamashita
et al. 2007 ). In another recent study, side population cells increased significantly in
Reinke’s space of an injured vocal fold starting on day 3, with a peak at day 7, fol-
lowed by a decrease back to baseline values on day 14 (Gugatschka et al. 2011 ).
These cells in the maculae flavae participated in the early stages of wound healing
(Gugatschka et al. 2011 ). The two investigation cited here suggest that the anterior
9 The Macula Flava of the Human Vocal Fold as a Stem Cell Microenvironment