dr. Zádori Anita - Semmelweis Egyetem Doktori Iskola

Summary
Data obtained from in vitro and in vivo studies on NE-4C neuroectodermal stem cells
and on sub-clones expressing histological markers demonstrated that the intracerebral
fate of implanted neural stem cells is governed by the actual state of the host
environment.
� Non-induced stem cells do not survive in, and can not integrate into the intact
adult brain parenchyma. In contrast, implanted stem cells survive for long (>60 days)
time in damaged brain cortices and can repopulate lesioned zones. The implanted
neural stem cells, however, do not differentiate to neurons either in lesioned or in
intact adult brain (Zádori, Ágoston et al., Neuropathol Appl Neurobiol. 2007
Oct;33(5):510-22).
� NE-4C neural stem cells can survive inside of some glioma-type neoplastic
tissues, but can not „find” the tumors inside the brain indicating that the investigated
tumours do not produce (enough) chemotactic signals to attract stem cells (Demeter
et al., Neurosci Res. 2005 53(3):331-42).
� Neural precursors at early stages of in vitro induced neuronal differentiation did
not show improved tissue-integration or in situ neuron formation in comparison to
non-committed stem cells.
� In vitro, non-induced stem cells grow readily at low (1%) oxygen concentration
and, apparently, are not damaged by hypoxia. Committed neural precursors, on the
other hand, display increased sensitivity to hypoxia. At defined stages of neural
differentiation, low O2-tension reduces the rates of neuron-production, markedly (*).
� The hypoxic environment in lesioned cortices seems to inhibit local neuron-
production, but does not prevent the proliferation of the implanted stem cells.
� Hyperbaric oxygen therapy reduces both, the intracerebral cell proliferation and
apoptosis at the lesion site, and makes the environment more permissive for
formation of neurons (*). (*: Zádori et al. 2010, submitted)
Our studies proved, that the fate of implanted neural stem cells is determined by the
host environment. The intracerebral neuron-formation was not improved by implanting
committed progenitors at early phase of neural commitment. Among the parameters of
the host environment, oxygen tension is one of the essential regulators of the stem cell
fate.
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