In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain

Theus, Michelle H.; Wei, Ling; Cui, Lin; Francis, Kevin; Hu, Xinyang; Keogh, Christine; Yu, Shan Ping

doi:10.1016/j.expneurol.2007.12.020

Cited by 221 publications

(265 citation statements)

References 54 publications

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“…However, cells treated under these conditions were often compared to cells cultured under air, incorrectly inferring that this oxygenation was representative of "healthy" tissues, and studies have often used short-term decreases in O 2 concentration [4,5], rather than longer periods associated with disease. Additionally, air has been used to represent post-reperfusion oxygenation when modelling reperfusion events in vitro [55,56].…”

Section: Discussionmentioning

confidence: 99%

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Ferguson

Smerdon

Harries

et al. 2018

Free Radical Biology and Medicine

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In vivo, mammalian cells reside in an environment of 0.5-10% O 2 (depending on the tissue location within the body), whilst standard in vitro cell culture is carried out under room air. Little is known about the effects of this hyperoxic environment on treatment-induced oxidative stress, relative to a physiological oxygen environment. In the present study we investigated the effects of long-term culture under hyperoxia (air) on photodynamic treatment. Upon photodynamic irradiation, cells which had been cultured long-term under hyperoxia generated higher concentrations of mitochondrial reactive oxygen species, compared with cells in a physioxic (2% O 2 ) environment. However, there was no significant difference in viability between hyperoxic and physioxic cells. The expression of genes encoding key redox homeostasis proteins and the activity of key antioxidant enzymes was significantly higher after the long-term culture of hyperoxic cells compared with physioxic cells. The induction of antioxidant genes and increased antioxidant enzyme activity appear to contribute to the development of a phenotype that is resistant to oxidative stress-induced cellular damage and death when using standard cell culture conditions. The results from experiments using selective inhibitors suggested that the thioredoxin antioxidant system contributes to this phenotype. To avoid artefactual results, in vitro cellular responses should be studied in mammalian cells that have been cultured under physioxia. This investigation provides new insights into the effects of physioxic cell culture on a model of a clinically relevant photodynamic treatment and the associated cellular pathways.

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Section: Discussionmentioning

confidence: 99%

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Ferguson

Smerdon

Harries

et al. 2018

Free Radical Biology and Medicine

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show abstract

“…Other diseases in which conventional immunosuppressive therapies fail may provide a rationale for the use of MSC-based therapeutic approaches [66][67][68]. MSC infusions may also play an important role in regulating inflammatory diseases of the central nervous system, although their interactions with the blood brain barrier have not been fully elucidated [67,69,70].…”

Section: Clinical Impressions and Future Implicationsmentioning

confidence: 99%

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

Borjesson

Peroni

2011

Clinics in Laboratory Medicine

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“…Hypoxic preconditioning of stem cells before transplantation may improve the survival and therapeutic effects of implanted cells. 8 The role of Glu in the pathophysiology of neurodegenerative diseases mostly revolves around its excitotoxic effects as a common mechanism of neuronal damage in AD, PD, stroke, neurotrauma and MS. 9 One of the factors known to protect different types of neural cells against both hypoxia-and Glu-induced cytotoxicity is erythropoietin (EPO). Its protective and regenerative effects have been shown for a broad range of neurodegenerative diseases in both experimental and clinical trials; EPO enhances neurogenesis and provides neuroprotection during experimental stroke.…”

mentioning

confidence: 99%

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

et al. 2009

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Mesenchymal stem cells (MSCs) can ameliorate symptoms in several neurodegenerative diseases. However, the toxic environment of a degenerating central nervous system (CNS) characterized by hypoxia, glutamate (Glu) excess and amyloid beta (Abeta) pathology may hamper the survival and regenerative/replacing capacities of engrafted stem cells. Indeed, human MSC (hMSC) exposed to hypoxia were disabled in (i) the capacity of their muscarinic receptors (mAChRs) to respond to acetylcholine (ACh) with a transient increase in intracellular [Ca 2 þ ], (ii) their capacity to metabolize Glu, reflected by a strong decrease in glutamine synthetase activity, and (iii) their survival on exposure to Glu. Cocultivation of MSC with PC12 cells expressing the amyloid precursor protein gene (APPsw-PC12) increased the release of IL-6 from MSC. HMSC exposed to erythropoietin (EPO) showed a cholinergic neuron-like phenotype reflected by increased cellular levels of choline acetyltransferase, ACh and mAChR. All their functional deficits observed under hypoxia, Glu exposure and APPsw-PC12 cocultivation were reversed by the application of EPO, which increased the expression of Wnt3a. EPO also enhanced the metabolism of Abeta in MSC by increasing their neprilysin content. Our data show that cholinergic neuron-like differentiation of MSC, their functionality and resistance to a neurotoxic environment is regulated and can be improved by EPO, highlighting its potential for optimizing cellular therapies of the CNS.

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In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain

Cited by 221 publications

References 54 publications

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

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