Biomedical Engineering Reference
In-Depth Information
aggregations underneath, called the anlage of dermal papillae (Davidson and
Hardy, 1952). In the absence of dermal papilla signaling, the embryonic basal
cells stay as epidermal cells. The committed hair germ cells then begin to grow
obliquely downward into the dermis and the advancing extremity becomes
bulbous, gradually enveloping the mesodermal papilla. At this stage, two to three
epithelial swellings appear on the posterior wall of the follicle and they eventu-
ally become the sebaceous gland, the apocrine gland and the arrector muscle
attachment site (Rook
et al.,
1986).
6.4 Experimental models for predicting cellular
interactions
Based on the classic transplant experiments where researchers mix-and-matched
epidermis and dermis from different parts of the body, it has been hypothesized
that epidermal growth and differentiation is controlled by epithelial-mesenchy-
mal interactions. However, little is known about the exact mechanisms of this
interaction owing to the number of variables involved, such as the different
dermal cell types and the superimposed influences of systemic factors in the
blood circulation.
6.4.1
The
in vitro
model
In vitro
model systems have been developed to mimic epidermal-dermal interac-
tions and to study regulation of epidermal cell proliferation and differentiation
(Sawyer and Fallow, 1983). These models have shown that coculture on postmitotic
mouse or human dermal fibroblasts are required to support human keratinocyte
growth at clonal densities in serum-containing medium. Under conventional
(submerged) culture conditions, keratinocyte proliferation is the predominant
event while terminal differentiation and tissue organization are reduced or atypical
compared to the
in vivo
situation (Holbrook and Hennings, 1983). However, using
organotypic culture systems where keratinocytes are cultured at an air-liquid
interface on fibroblast-embedding collagen gels, improvement of tissue architec-
ture and induction of terminal differentiation markers have been achieved (Kopan
et al.,
1987).
With the help of such an elaborated
in vitro
cultural system that can closely
imitate the
in vivo
situation, it is possible to examine the functions of individual
factors during epithelial-mesenchymal interactions and a number of extracellu-
lar regulators controlling the balance between epidermal growth and terminal
differentiation have been identified. These factors can be categorically assigned
to two groups based on their mitogenic activity on keratinocytes, positive growth
regulators and negative growth regulators. Stimulators of keratinocyte growth
include EGF, TGF-
α
, low concentration of retinoic acid (Kopan and Fuchs,
