Biology Reference
In-Depth Information
TISSUE ENGINEERING AS A TECHNIQUE FOR
MODELLING MORPHOGENESIS
'Tissue engineering' is a term that spans a wide range of techniques. At its closest to basic
science, tissue engineering seems only a modest extension of cell culture; at its most applied,
it is an aspect of regenerative surgery.
1
Much current tissue engineering has little to do with
morphogenesis, consisting as it does of attempts to introduce a patient's stem cells into a pre-
existing, pre-shaped extracellular matrix, typically obtained by using detergent washed to
remove living cells from a donor tissue such as a trachea.
2
The field is more interesting,
from the point of view of modelling morphogenesis, where it seeks to persuade simple collec-
tions of cells to react to unnatural environments or to assemble themselves without a pre-
existing template.
An experiment from the very earliest days of tissue culture clearly illustrates the approach
of confronting cellswith anunnatural environment. Its resultswere very useful in illuminating
an important problem in the development of the vertebrate peripheral nervous system.
)
The
spinal cord is connected to trunk and limb muscles by motor axons that run together in
nerves. During development, growth cones of these axons travel through the somites that
flank the neural tube. Specifically, they travel only through each somite's anterior half
and thus avoid becoming trapped in the posterior halves that will become the vertebral
bone (Chapter 11). In principle, the pattern of axon emission might be intrinsic to the neural
tube, or could be imposed on it by somites. In 1911, the tissue culture pioneer M.T. Burrows
removed neural tubes from embryos and placed them in an artificial environment in which
a homogenous extracellular matrix flanked all of the neural tube, with no somites being
present.
3
Under these circumstances, the entire neural tube emitted axons with no trace
of the normal segmented pattern, indicating that the control of the normal segmented
pattern was under the control of somites and not innate to the neural tube itself. This exper-
iment, although very simple compared with ones that can be conducted now, nevertheless
illustrates the advantages of working with a simple developing system engineered from just
a few embryonic components.
A similar system, on a similar topic, has been used to explore the reason that sensory nerves
penetrate the dermal but not the epidermal layer of the skin. The two possibilitieswere that the
dermis is strongly attractive, or that the epidermis is actively unattractive. The possibilities
were tested using a simple engineered system in which axons emerging from chick sensory
ganglia were confronted, after a short (1 mm) interval of cell-free, poly-lysine-coated culture
plastic, with small explants of either the dermal or the epidermal layer of the skin.
4
The direc-
tion and velocity of growth cones emerging from the ganglia were unaffected by a neighbour-
ing explant of dermis and growth cones heading towards that tissue carried on to invade it.
When an explant of epidermis was present, however, it had a dramatic effect on growth
cone behaviour: growth cones heading initially towards the epidermis veered away to run
around it, avoiding contact (
Figure 27.1
). This strongly implied that the epidermis secreted
something that repelled growth cones (growth cone repulsion is described in Chapter 11).
The repulsion has since been shown to bemediated inmammals by EphrinA4
ref5
and in chicks
)
Although, in this case, the developmental significance of the result was understood much later.
