Ga. Foster et Bmj. Stringer, Genetic regulatory elements introduced into neural stem and progenitor cell populations, BRAIN PATH, 9(3), 1999, pp. 547-567
The genetic manipulation of neural cells has advantage in both basic biolog
y and medicine. Its utility has provided a clearer understanding of how the
survival, connectivity, and chemical phenotype of neurones is regulated du
ring, and after, embryogenesis. Much of this achievement has come from the
recent generation by genetic means of reproducible and representative suppl
ies of precursor cells which can then be analyzed in a variety of paradigms
. Furthermore, advances made in the clinical use of transplantation for neu
rodegenerative disease have created a demand for an abundant, efficacious a
nd safe supply of neural cells for grafting. This review describes how gene
tic methods, in juxtaposition to epigenetic means, have been used advantage
ously to achieve this goal. In particular, we detail how gene transfer tech
niques have been developed to enable cell immortalization, manipulation of
cell differentation and commitment, and the controlled selection of cells f
or purification or safety purposes, In addition, it is now also possible to
genetically modify antigen presentation on cell surfaces. Finally, there i
s detailed the transfer of therapeutic products to discrete parts of the ce
ntral nervous system (CNS), using neural cells as elegant and sophisticated
delivery vehicles.
In conclusion, once the epigenetic and genetic controls over neural cell pr
oduction, differentiation and death have been more fully determined, provid
ing a mixture of hard-wired elements and more flexibly expressed characteri
stics becomes feasible. Optimization of the contributions and interactions
of these two controlling systems should lead to improved cell supplies for
neurotransplantation.