Abstract
BackgroundNeural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existing in vitro studies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).ResultsAdult CSF increased the survival rate of adult human NSCs compared to standard serum free culture media during both stem cell maintenance and differentiation. The presence of CSF promoted differentiation of NSCs leading to a faster loss of their self-renewal capacity as it is measured by the proliferation markers Ki67 and BrdU and stronger cell extension outgrowth with longer and more cell extensions per cell. After differentiation in CSF, we found a larger number of GFAP+ astroglial cells compared to differentiation in standard culture media and a lower number of β-tubulin III+ neuronal cells.ConclusionsOur data demonstrate that adult human leptomeningeal CSF creates a beneficial environment for the survival and differentiation of adult human NSCs. Adult CSF is in vitro a strong glial differentiation stimulus and leads to a rapid loss of stem cell potential.
Highlights
Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases
Our results showed a significantly higher survival rate of NSCs in cerebrospinal fluid (CSF) compared to standard expansion medium with 6.9 ± 1.9% of necrotic cells in CSF versus 46.0 ± 12.9% in expansion medium (P = 0.013; Fig. 1)
Addition of the bone morphogenic protein (BMP) inhibitor Noggin did not significantly increase cell death rates compared to CSF without Noggin (5.2 ± 2.4% of necrotic cells, P = 0.54; Fig. 1)
Summary
Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. The isolation and successful long-term expansion of human NSCs from the adult hippocampus, the adult olfactory bulb and adult post-mortem tissues have been reported [16,17,18,19,20]. In these studies, ahNSCs have successfully been expanded for more than 30 population doublings using serum-free culture medium which is normally supplemented with the mitogenes epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2). Removal of the mitogenes leads to spontaneous differentiation of adult NSCs into neurons, astroglia and oligondendroglia [16,17,18,19,20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
