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Hypoxia in the regulation of neural stem cells

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Abstract

In aerobic organisms, oxygen is a critical factor in tissue and organ morphogenesis from embryonic development throughout post-natal life, as it regulates various intracellular pathways involved in cellular metabolism, proliferation, survival and fate. In the mammalian central nervous system, oxygen plays a critical role in regulating the growth and differentiation state of neural stem cells (NSCs), multipotent neuronal precursor cells that reside in a particular microenvironment called the neural stem cell niche and that, under certain physiological and pathological conditions, differentiate into fully functional mature neurons, even in adults. In both experimental and clinical settings, oxygen is one of the main factors influencing NSCs. In particular, the physiological condition of mild hypoxia (2.5–5.0% O2) typical of neural tissues promotes NSC self-renewal; it also favors the success of engraftment when in vitro-expanded NSCs are transplanted into brain of experimental animals. In this review, we analyze how O2 and specifically hypoxia impact on NSC self-renewal, differentiation, maturation, and homing in various in vitro and in vivo settings, including cerebral ischemia, so as to define the O2 conditions for successful cell replacement therapy in the treatment of brain injury and neurodegenerative diseases.

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Acknowledgements

This work was supported by the Italian Telethon grant GGP 10066 (to D.D.) and by the no-profit Foundations Neurothon, Cellule Staminali (Terni, Italy) and Borgonovo, the research Institute Casa Sollievo della Sofferenza (S.Giovanni Rotondo, Italy), Stem Cell Factory (Ospedale S.Maria, Terni), which are funding and providing the necessary support to start up the clinical trial for ALS patients in Italy (information available at the site: http://www.adottaunacellula.org). A special thank you to Luigi Carlessi, Cristina Zalfa, Elena Fusar Poli and Guido Santilli for their precious technical and scientific support. Prof. Angelo Vescovi supported us with important suggestions and critical discussions.

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  1. Department of Biotechnologies and Biosciences, University of Milano-Bicocca, Milan, Italy

    Lidia De Filippis

  2. Department of Experimental Oncology, Fondazione IRCSS Istituto Nazionale Tumori, Via Amadeo 42, 20133, Milan, Italy

    Domenico Delia

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  1. Lidia De Filippis
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Correspondence to Lidia De Filippis.

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De Filippis, L., Delia, D. Hypoxia in the regulation of neural stem cells. Cell. Mol. Life Sci. 68, 2831–2844 (2011). https://doi.org/10.1007/s00018-011-0723-5

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