Development and Maturation of the Pediatric Human Vocal Fold Lamina Propria

Harvard University, Cambridge, Massachusetts, United States
The Laryngoscope (Impact Factor: 2.14). 02/2005; 115(1):4-15. DOI: 10.1097/01.mlg.0000150685.54893.e9
Source: PubMed


To identify characteristic patterns of maturation of the human vocal fold lamina propria as it develops into a mature structure.
Histologic evaluation of sectioned true vocal folds from 34 archived larynges ages 0 to 18 years using hematoxylin-eosin, trichrome, Alcian blue pH 2.5, Weigert reticular, and Miller's elastin stain.
Pathology department at a tertiary care children's hospital.
At birth and shortly thereafter, there exists a relative hypercellular monolayer of cells throughout the lamina propria. By 2 months of age, there are the first signs of differentiation into a bilaminar structure of distinct cellular population densities. Between 11 months and 5 years, two distinct patterns are seen: 1) this bilaminar structure and 2) a lamina propria where there exists a third more hypocellular region immediately adjacent to the vocalis muscle (this region is similar to the superficial hypocellular region found just deep to the surface epithelium). By 7 years of age, all of the specimens exhibit this transition between the middle and the deeper layers according to differential density of cell populations. A lamina propria structure defined by differential fiber composition (elastin and collagen fibers) is not present until 13 years of age and then is present throughout adolescence.
Using the classic adult model of fiber composition and density to differentiate the layered structure of the lamina propria of the human vocal fold may not adequately allow for a thorough description of the process of maturation and development. Rather, distinct regions of cell density are seen as early as 2 months postpartum, and the model of cellular distribution may serve better to describe the lamina propria as it develops. Cell-signaling processes that shape the formation of the lamina propria appear to produce layered populations of differential cell density that in turn will later produce differential fiber compositions. Early development therefore can be followed by evaluating the maturation of these differing cell populations. Future studies are needed to quantify these cell distribution patterns, to study the cell signaling processes that trigger this maturation, and to correlate these findings with mechanical modeling.

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    • "In other words, production is importantly " supralaryngeal, " with the tongue, mandible, and lips used to flexibly and dynamically create the many sounds of each different language. Human vocal-fold structure and response also show important developmental changes (Schweinfurth and Thibeault, 2008; Hartnick et al., 2005). One evident consequence is that the vibration regimes underlying the psycheshattering shrieks and screams characteristic of young children become difficult, if not impossible, for adults to produce. "

    Acoustics Today 01/2011; 7(4):24. DOI:10.1121/1.3684225
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    • "Other investigators have described the presence of fibrous structures , such as collagen and elastic fibres, in the lamina propria of the vocal folds of fetuses after 21 weeks of age (Fayoux et al. 2004). Despite the controversy regarding the distribution of extracellular matrix components in the vocal fold lamina propria, it has been established that after birth the vocal fold continues its process of development and maturation, mediated by exogenous stimuli, mainly phonation, until it attains the highly complex structure seen in adults (Hartnick et al. 2005). On the basis of these observations, and in the light of current knowledge regarding the ultrastructural and histochemical properties of elastic and collagenous system fibres, we conceived this study to investigate the structural organization of the lamina propria of the fetal vocal fold during the late prenatal period. "
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    ABSTRACT: Although it is currently believed that the vocal ligament of humans undergoes considerable development postnatally, there is no consensus as to the age at which it first emerges. In the newborn infant, the lamina propria has been described as containing a sparse collection of relatively unorganized fibres. In this study we obtained larynges from autopsy of human fetuses aged 7-9 months and used light and electron microscopy to study the collagenous and elastic system fibres in the lamina propria of the vocal fold. Collagen fibres were viewed using the Picrosirius polarization method and elastic system fibres were stained using Weigert's resorcin-fuchsin after oxidation with oxone. The histochemical and electron microscopic observations were consistent, showing collagen populations with an asymmetric distribution across different compartments of the lamina propria. In the central region, the collagen appeared as thin, weakly birefringent, greenish fibres when viewed using the Picrosirius polarization method, whereas the superficial and deep regions contained thick collagen fibres that displayed a strong red or yellow birefringence. These findings suggest that the thin fibres in the central region consist mainly of type III collagen, whereas type I collagen predominates in the superficial and deep regions, as has been reported in studies of adult vocal folds. Similarly, elastic system fibres showed a differential distribution throughout the lamina propria. Their distribution pattern was complementary to that of collagen fibres, with a much greater density of elastic fibres apparent in the central region than in the superficial and deep regions. This distribution of collagen and elastic fibres in the fetal vocal fold mirrors that classically described for the adult vocal ligament, suggesting that a vocal ligament has already begun to develop by the time of birth. The apparently high level of organization of connective tissue components in the newborn is in contrast to current hypotheses that argue that the mechanical stimuli of phonation are essential to the determination of the layered structure of the lamina propria and suggests that genetic factors may play a more significant role in the development of the vocal ligament than previously believed.
    Journal of Anatomy 12/2009; 215(6):692-7. DOI:10.1111/j.1469-7580.2009.01146.x · 2.10 Impact Factor
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    • "In contrast to the complex layered organization and variable matrix composition observed in the adult, newborn vocal folds are homogeneous structures (Hirano, 1983; Hirano and Sato, 1993). Recent analyses of pediatric human vocal folds from subjects ranging from postnatal to adolescence indicate that the vocal folds undergo extensive development and maturation into the early teens (Hartnick et al., 2005; Boseley and Hartnick, 2006). Consistent with the recognized contributions of externally applied mechanical forces in the development and homeostatic maintenance of many soft connective tissues, these observations suggest that the complex mechanical forces imposed during voice development may be an important epigenetic mechanism regulating tissue composition and mechanics. "
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    ABSTRACT: The composition and organization of the vocal fold extracellular matrix (ECM) provide the viscoelastic mechanical properties that are required to sustain high-frequency vibration during voice production. Although vocal injury and pathology are known to produce alterations in matrix physiology, the mechanisms responsible for the development and maintenance of vocal fold ECM are poorly understood. The objective of this study was to investigate the effect of physiologically relevant vibratory stimulation on ECM gene expression and synthesis by fibroblasts encapsulated within hyaluronic acid hydrogels that approximate the viscoelastic properties of vocal mucosa. Relative to static controls, samples exposed to vibration exhibited significant increases in mRNA expression levels of HA synthase 2, decorin, fibromodulin and MMP-1, while collagen and elastin expression were relatively unchanged. Expression levels exhibited a temporal response, with maximum increases observed after 3 and 5 days of vibratory stimulation and significant downregulation observed at 10 days. Quantitative assays of matrix accumulation confirmed significant increases in sulphated glycosaminoglycans and significant decreases in collagen after 5 and 10 days of vibratory culture, relative to static controls. Cellular remodelling and hydrogel viscosity were affected by vibratory stimulation and were influenced by varying the encapsulated cell density. These results indicate that vibration is a critical epigenetic factor regulating vocal fold ECM and suggest that rapid restoration of the phonatory microenvironment may provide a basis for reducing vocal scarring, restoring native matrix composition and improving vocal quality.
    Journal of Tissue Engineering and Regenerative Medicine 01/2009; 4(1):62-72. DOI:10.1002/term.219 · 5.20 Impact Factor
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