Biomedical Engineering Reference
In-Depth Information
2005). In neural stem cells derived from early embryos, BMPs appear to
promote both proliferation and neuronal differentiation. However, these
stem-like tumor cells may be susceptible to stimuli that alter the proliferation
of normal neural precursors. Treatment of this tumor stem cell population with
BMPs, which limit the proliferation of normal stem cells, blocks the ability of
these cells to form tumors upon transplantation. In contrast, neural stem cells
derived from older animals undergo astrocytic differentiation in response to
BMPs (Panchision et al. 2001). Preclinical trials are underway to assess the
utility of such an agent in curtailing glioma proliferation (Nakano et al. 2008).
Other studies have focused upon the migratory abilities of specific neural
stem cell lines, which may have the potential to deliver therapeutic substances to
specific sites in the brain (Aboody et al. 2000). Neural stem cells transplanted
into animal models of brain neoplasia were found near metastatic tumor cells
far from the site of their transplantation (Tang et al. 2003). These observations
suggest that neural stem cells engineered to deliver cell-specific cytotoxic agents
might be used to track down and destroy malignant cells. This would be
particularly useful if non-cycling cells could be targeted, as they often represent
the tumor fraction that survives adjuvant chemo- and radiation therapy regi-
mens (Hambardzumyan et al. 2006).
9 Conclusions
A new path has emerged in the clinical neurosciences, connecting neuro-
oncology with developmental neurobiology. The juvenile and adult human
brain, for many years thought to be composed of fully differentiated cells
contains multiple neuronal and glial progenitor cell populations, most notably
in the subventricular zone and white matter. As we elucidate the lineage
relationships of the ventricular and subventricular zone, from embryonic stages
to adulthood, it may eventually be possible to identify stem or progenitor cell
types at risk for transformation. This will allow the design of mouse tumor
models in which specific populations of progenitor cell are targeted. A revised
pathological classification system of tumors may emerge that will link tumor
subtypes to specific developmental lineages. This, in turn, could facilitate the
discovery of new markers for tumor progression, techniques for earlier cancer
detection, and novel targeted therapies. Our success, however, depends largely
upon our ability to understand the natural biology of these poorly understood
germinal regions.
References
Aboody KS, Brown A, Rainov NG, et al. Neural stem cells display extensive tropism for
pathology in adult brain: evidence from intracranial gliomas. Proceedings of the National
Academy of Sciences of the United States of America 2000;97(23):12846-51.
