Mild Hypoxia Enhances Proliferation and Multipotency of Human Neural Stem Cells

Santilli, Guido; Lamorte, Giuseppe; Carlessi, Luigi; Ferrari, Daniela; Nodari, Laura Rota; Binda, Elena; Delia, Domenico; Vescovi, Angelo L.; Filippis, Lidia De

doi:10.1371/journal.pone.0008575

Cited by 170 publications

(165 citation statements)

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“…Physiological microenvironments play a crucial role in maintenance of stem cell properties, and the oxygen concentration is an important component of the stem cell niche (Peerani and Zandstra 2010;Santilli et al 2010). In the present study, hypoxia provokes MSCs proliferation, and increases ALP activity and production of both Col I/III.…”

Section: Discussionsupporting

confidence: 50%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.

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Section: Discussionsupporting

confidence: 50%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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“…For example, hematopoietic stem cells are maintained in hypoxic niches in bone marrow (Parmar et al, 2007). Interestingly, hypoxia also prevents the differentiation of neural stem cells and promotes the maintenance of self-renewal potential of embryonic stem (ES) cells (Studer et al, 2000;Marrison et al, 2000;Ezashi et al, 2005;Santilli et al, 2010). In addition, restricted oxygen concentrations have been shown to enhance the production of induced pluripotent stem cells (iPSC) (Yoshida et al, 2009).…”

Section: Hypoxic Responses In Glioblastoma Stem Cellsmentioning

confidence: 99%

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

et al. 2010

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Glioblastomas (GBMs) are highly lethal primary brain tumors. Despite current therapeutic advances in other solid cancers, the treatment of these malignant gliomas remains essentially palliative. GBMs are extremely resistant to conventional radiation and chemotherapies. We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells (GSCs) promotes therapeutic resistance. We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth, which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs. Furthermore, stem cell-like cancer cells (cancer stem cells) have been shown to promote metastasis. Although GBMs rarely metastasize beyond the central nervous system, these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection, and GSCs display an aggressive invasive phenotype. These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment. Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells, but also display critical distinctions that provide important clues into useful therapeutic targets. In this review, we summarize the current understanding and advances in glioma stem cell research, and discuss potential targeting strategies for future development of anti-GSC therapies.

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“…In addition, near-physiological oxygen tensions (5-6%) improve the efficiency of induced pluripotent stem cell generation (79). Several studies on in vitro differentiation of neural stem cells have shown that low oxygen levels promote proliferation, survival and multipotency as compared to normoxic oxygen levels (80)(81)(82)(83)(84)(85)(86). Hematopoietic stem cells (HSCs) in the bone marrow have been proposed to exist in a low oxygen milieu (87,88).…”

Section: Hypoxia and The Stem Cell Phenotypementioning

confidence: 99%

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Mohlin

Wigerup

Påhlman

2011

Seminars in Cancer Biology

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Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage.Mohlin, Sofie; Wigerup, Caroline; Påhlman, Sven Link to publication Citation for published version (APA): Mohlin, S., Wigerup, C., & Påhlman, S. (2011). Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage. Seminars in Cancer Biology, 21(4), 276-282. DOI: 10.1016276-282. DOI: 10. /j.semcancer.2011 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Neural crest and development of the sympathetic nervous systemThe sympathetic nervous system (SNS) originates from the neural crest, an ephemeral structure during vertebrate development. Located along the neural fold, cells on the neural tube in the ectoderm give rise to the neural crest, in turn generating different derivatives, such as the cranial, hindbrain, vagal and trunk neural crest (reviewed in (9)). Trunk neural crest cells migrate from the neural tube along two defined routes, with one group of cells migrating early along a ventral pathway, giving rise to glial cells and neurons, whereas a later migrating group of cells follows a lateral pathway and gives rise to melanocytes in the skin (10, 11). These mutations were rare in all four studies indicating locus heterogeneity for predisposition of inherited disease, but still demonstrated the importance of the PHOX2B gene in neuroblastoma oncogenesis and initiation (Fig. 1) (58), and Fig. 1). Neuroblastoma differentiation stage and clinical outcomeThere is a well-documented difference in aggressive behavior between the morphologically undifferentiated (neuroblastoma proper) and the differentiated (ganglioneuroblastoma, Cellular adaptation to hypoxiaThe biological consequences of hypoxia involve induced angiogenesis, a switch in glucose metabolism and increased invasion and migration capacities, changes that stimulate tumor progression. The hypoxic response is mainly mediated by stabilization of the hypoxia inducible factor (HIF) proteins. HIFs are heterodimeric transcription factors composed of an oxygen sensitive  subunit and a constitutively expressed  subunit. At physiological oxygen levels, the  subunit is hydroxylated by the oxygen-dependent prolyl hydroxylases (PHDs), leading to interaction with the von Hippel Lindau-ubiquitin ligase complex, followed by ubiquitination and proteasomal degradation. At hypoxia, the PHDs are inactive leading to the 9 stabilization of the HIF- subunits, and by dimerization with the  subunit the comple...

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Mild Hypoxia Enhances Proliferation and Multipotency of Human Neural Stem Cells

Cited by 170 publications

References 44 publications

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

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