During the last two decades stem cell biology has
changed the field of basic research in life science as well as our perspective
of its possible outcomes in medicine. At the beginning of the nineties, the
discovery of neural stem cells in the mammalian central nervous system (CNS) made
the generation of new neurons a real biological process occurring in the adult
brain. Since then, a vast community of neuroscientists started to think in
terms of regenerative medicine as a possible solution for incurable CNS
diseases, such as traumatic injuries, stroke and neurodegenerative disorders.
Nevertheless, in spite of the remarkable expansion of the field, the
development of techniques to image neurogenesis in vivo, sophisticated in vitro
stem cell cultures, and experimental transplantation techniques, no efficacious
therapies capable of restoring CNS structure and functions through cell
replacement have been convincingly developed so far. Deep anatomical,
developmental, molecular and functional investigations have shown that new
neurons can be generated only within restricted brain regions under the control
of specific environmental signals. In the rest of the CNS, many problems arise
when stem cells encounter the mature parenchyma, which still behaves as
'dogmatically' static tissue. More recent studies have added an additional
level of complexity, specifically in the context of CNS structural plasticity, where
stem cells lie within germinal layer-derived neurogenic sites whereas
progenitor cells are widespread through the CNS.
Hence, two decades after the seminal discovery of
neural stem cells, the real astonishing fact is the occurrence of such cells in
a largely nonrenewable tissue. Still, the most intriguing question is which
possible functional or evolutionary reasons might justify such oddity. In other
self-renewing tissues, such as skin, cornea, and blood, the role of stem cells
in the tissue homeostasis is largely known and efficacious stem cell therapies
are already available. The most urgent question is whether and how the
potential of neural stem cells could be exploited within the harsh territory of
the mammalian CNS. In this case, unlike other tissues, more intense and
time-consuming basic research is required before achieving a regenerative
outcome. The road of such research should travel through a better knowledge of
several aspects which are still poorly understood, including the developmental
programs leading to postnatal brain maturation, the heterogeneity of progenitor
cells involved, the bystander effect that stem cell grafts exert even in the
absence of cell replacement, and the cohort of stem cell-to-tissue interactions
occurring both in homeostatic and pathological conditions.
In this book, the experience and expertise of many
leaders in neural stem cell research are gathered with the aim of making the
point on a number of extremely promising, yet unresolved, issues.
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