@phdthesis{Buddensiek2011, author = {Judith Buddensiek}, title = {Influence of human Cerebrospinal fluid on the behaviour of human adult and fetal murine neural stem cells}, journal = {Influence of human Cerebrospinal fluid on the behaviour of human adult and fetal murine neural stem cells}, url = {https://nbn-resolving.org/urn:nbn:de:gbv:9-001115-9}, year = {2011}, abstract = {Neurodegenerative disorders are characterized by a progressive loss of structure or function of neurons or glial cells in the brain or spinal cord. Thus, the prospect of replacing the missing or damaged nerve tissue is very attractive. A promising source for cell replacement therapies for neurodegenerative disorders are neural stem cells (NSCs). As an alternative to the intracerebral stereotactical surgical cell transplantation, the administration of NSCs via cerebrospinal fluid (CSF) has recently been proposed as a non- traumatic transplantation method into the brain. However, cell survival and intraparenchymal migration of the transplants were limited. As a possible reason the low nutrition content of CSF was discussed. Furthermore, CSF was recently reported to be an important milieu for controlling stem cell processes in the developing brain, which is why we studied the effects of adult human leptomeningeal CSF on the behaviour of fetal murine (fmNSCs) and adult human NSCs (ahNSCs). The central findings of our studies are that, in vitro, adult human leptomeningeal CSF: (i) enhances the survival rate of ahNSCs and fmNSCs during expansion and differentiation compared to standard culture/differentiation media (ii) enhances NSC differentiation and extension outgrowth velocity, leading to a faster loss of self-renewing capacity (iii) has an astrogliogenesis facilitating effect on ahNSCs and fmNSCs and inhibits neurogenesis in fmNSCs. A low survival rate of intrathecally applied NSCs due to a low nutrition content of CSF therefore seems improbable. Still, adult human leptomeningeal CSF leads to a quicker loss of stem cell potential and enhances extension outgrowth velocity. This may cause an attachment of injected NSCs at the wall of the ventricle where they are injected and impede sufficient migration into the CNS. Additionally, CSF promotes astrogliogenesis and in fmNSCs even inhibits the differentiation into neurons. This may also be a disadvantageous CSF effect, impeding intracerebral NSC differentiation into required neurons after non- traumatic NSCs transplantation. For these reasons, future studies are demanded to gain deeper knowledge about CSF contents, their influence on NSCs and ways of controlling them before intrathecally NSC transplantation may become a functional alternative to surgical transplantation methods.}, language = {de} }