Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner

Drela, Katarzyna; Sarnowska, Anna; Siedlecka, Patrycja; Szabłowska-Gadomska, Ilona; Wielgoś, Mirosław; Jurga, Marcin; Lukomska, B; Domanska-Janik, Krystyna

doi:10.1016/j.jcyt.2014.02.009

Cited by 73 publications

(61 citation statements)

References 66 publications

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“…It seems that Hif-1 initiates the physioxic response, which is maintained by other O 2 mediators such as Hif-2. Similar findings were observed in mesenchymal stem cell culture, where low O 2 preferentially increased the expression of Hif-2α instead of Hif-1α (Drela et al, 2014). In that case, rather the knockout of Hif-2α would leave to decreased protein levels of active ß-catenin in physioxic cells, which will clearly be of interest to examine.…”

Section: Discussionsupporting

confidence: 67%

Oxygen regulates proliferation of neural stem cells through Wnt/β-catenin signalling

Braunschweig¹,

Meyer²,

Wagenführ³

et al. 2015

Molecular and Cellular Neuroscience

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Section: Discussionsupporting

confidence: 67%

Oxygen regulates proliferation of neural stem cells through Wnt/β-catenin signalling

Braunschweig¹,

Meyer²,

Wagenführ³

et al. 2015

Molecular and Cellular Neuroscience

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“…Spontaneous differentiation of H1 hES cells is increased at 20% oxygen while contrarily, physiological oxygen results in better EB formation (Ezashi et al 2005). Regulating the oxygen concentration noticeably improves the differentiation efficiency of several cell types from precursor populations, including mouse and human pancreatic b-cells (Cechin et al 2014, Hakim et al 2014, human endothelial cells (Kusuma et al 2014) and human mesenchymal stem cells (Drela et al 2014). It remains to be seen whether modulating oxygen concentrations during directed differentiation of hES cells will increase differentiation efficiency.…”

Section: Targeted Mesendoderm Induction Reveals Asynchronous Differenmentioning

confidence: 99%

Distinct profiles of human embryonic stem cell metabolism and mitochondria identified by oxygen

Lees¹,

Rathjen²,

Sheedy³

et al. 2015

Reproduction

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Oxygen is a powerful regulator of cell function and embryonic development. It has previously been determined that oxygen regulates human embryonic stem (hES) cell glycolytic and amino acid metabolism, but the effects on mitochondria are as yet unknown. Two hES cell lines (MEL1, MEL2) were analyzed to determine the role of 5% (physiological) and 20% (atmospheric) oxygen in regulating mitochondrial activity. In response to extended physiological oxygen culture, MEL2 hES cells displayed reduced mtDNA content, mitochondrial mass and expression of metabolic genes TFAM, NRF1, PPARa and MT-ND4. Furthermore, MEL2 hES cell glucose consumption, lactate production and amino acid turnover were elevated under physiological oxygen. In stark contrast, MEL1 hES cell amino acid and carbohydrate use and mitochondrial function were relatively unaltered in response to oxygen. Furthermore, differentiation kinetics were delayed in the MEL1 hES cell line following BMP4 treatment. Here we report the first incidence of metabolic dysfunction in a hES cell population, defined as a failure to respond to oxygen concentration through the modulation of metabolism, demonstrating that hES cells can be perturbed during culture despite exhibiting the defining characteristics of pluripotent cells. Collectively, these data reveal a central role for oxygen in the regulation of hES cell metabolism and mitochondrial function, whereby physiological oxygen promotes glucose flux and suppresses mitochondrial biogenesis and gene expression.

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“…A recent study by Reppel et al demonstrated better chondrogenesis of stromal cells from Wharton's Jelly in hypoxic condition (Reppel et al, 2014). On the contrary, cell expansion in low oxygen environments has been suggested to maintain UCSCs in undifferentiated state (Drela et al, 2014). In our study, expression of OCT4A, NANOG and SOX2 is elevated in UCSCs-MC during monolayer expansion in both normoxic and hypoxic environments (albeit at higher levels in low oxygen conditions), which evidently shows that cells are kept in undifferentiated state during monolayer growth.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cells from human umbilical cords display poor chondrogenic potential in scaffold-free three dimensional cultures

Islam

Hansen²,

Mennan³

et al. 2016

eCM

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Many researchers world over are currently investigating the suitability of stromal cells harvested from foetal tissues for allogeneic cell transplantation therapies or for tissue engineering purposes. In this study, we have investigated the chondrogenic potential of mesenchymal stromal cells (MSCs) isolated from whole sections of human umbilical cord or mixed cord (UCSCs-MC), and compared them with cells isolated from synovial membrane (SMSCs), Hoffa's fat pad (HFPSCs) and cartilage. All MSCs were positive for surface markers including CD73, CD90, CD105, CD44, CD146 and CD166, but negative for CD11b, CD19, CD34, CD45 and HLA-DR in addition to CD106 and CD271. Chondrogenic potential of all cell sources was studied using 3D pellet cultures incubated in the presence of different combinations of anabolic substances such as dexamethasone, IGF-1, TGF-β1, TGF-β3, BMP-2 and BMP-7. BMP-2 and dexamethasone in combination with TGF-β1 or TGF-β3 excelled at inducing chondrogenesis on SMSCs, HFPSCs and chondrocytes, as measured by glycosaminoglycans and collagen type II staining of pellets, quantitative glycosaminoglycan expression, quantitative PCR of cartilage signature genes and electron microscopy. In contrast, none of the tested growth factor combinations was sufficient to induce chondrogenesis on UCSCs-MC. Moreover, incubation of UCSCs-MC spheroids in the presence of cartilage pieces or synovial cells in co-cultures did not aid chondrogenic induction. In summary, we show that in comparison with MSCs harvested from adult joint tissues, UCSCs-MC display poor chondrogenic abilities. This observation should alert researchers at the time of considering UCSCs-MC as cartilage forming cells in tissue engineering or repair strategies.

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Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner

Cited by 73 publications

References 66 publications

Oxygen regulates proliferation of neural stem cells through Wnt/β-catenin signalling

Oxygen regulates proliferation of neural stem cells through Wnt/β-catenin signalling

Distinct profiles of human embryonic stem cell metabolism and mitochondria identified by oxygen

Mesenchymal stromal cells from human umbilical cords display poor chondrogenic potential in scaffold-free three dimensional cultures

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