Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro

Experimental Cell Research
Lynda S WrightClive N Svendsen

Abstract

Isolation of a true self-renewing stem cell from the human brain would be of great interest as a reliable source of neural tissue. Here, we report that human fetal cortical cells grown in epidermal growth factor expressed low levels of telomerase and telomeres in these cultures shortened over time leading to growth arrest after 30 weeks. Following leukemia inhibitory factor (LIF) supplementation, growth rates and telomerase expression increased. This was best demonstrated following cell cycle synchronization and staining for telomerase using immunocytochemistry. This increase in activity resulted in the maintenance of telomeres at approximately 7 kb for more than 60 weeks in vitro. However, all cultures displayed a lack of oligodendrotye production, decreases in neurogenesis over time and underwent replicative senescence associated with increased expression of p21 before 70 weeks in vitro. Thus, under our culture conditions, these cells are not stable, multipotent, telomerase expressing self-renewing stem cells. They may be more accurately described as human neural progenitor cells (hNPC) with limited lifespan and bi-potent potential (neurons/astrocytes). Interestingly, hNPC follow a course of proliferation, neuronal production...Continue Reading

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Citations

Oct 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marianela CandolfiMaria G Castro
Oct 27, 2010·Journal of Biomedicine & Biotechnology·Jaroslav MokryRomana Ivancakova
Dec 3, 2008·Cell Transplantation·Soshana BehrstockClive N Svendsen
Jul 16, 2009·JAMA : the Journal of the American Medical Association·Ajay K YadavMarkus Bredel
Sep 10, 2009·Developmental Neuroscience·Anita BhattacharyyaClive N Svendsen
Nov 10, 2009·PloS One·Dhruv SareenClive N Svendsen
Oct 16, 2010·PloS One·Thomas M KeenanClive N Svendsen
Sep 10, 2011·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Genevieve Gowing, Clive N Svendsen
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Sep 17, 2013·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Kerry RennieMahmud Bani-Yaghoub
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