PHCbi-Panasonic eBook - 8

Cell Therapy Today * New Developments in Immunotherapy * Benefits of Oxygen Control in the Cell Culture Incubator

homeostasis and key pathways, such as angiogenesis, glycolysis, and erythropoiesis.
Genes regulated by HIF are important for
improving cell survival and reducing cell stress
which occurs physiologically during fetal development or ischemia.8
HIF also promotes normal physiological cell
differentiation and proliferation by regulating
the expression of genes that control cellular
glucose uptake and metabolism. One gene,
vascular endothelial growth factor (VEGF-A), is
critical for the cellular process of angiogenesis
(blood vessel growth) and is upregulated with
the presence of HIF.
Blood vessel growth helps facilitate oxygen
delivery to hypoxic tissues. VEGF also has a key
role in fetal development where hypoxic
microenvironments are typical.9
In addition, HIF has an important role in patho-

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physiologic or disease conditions, such as cancer,
where abnormalities often create hypoxic states
in certain tissues. Rapid cell division during tumor
progression generates hypoxic conditions that
lead to activation of HIF, which, in turn, initiates
cell survival processes that maintain homeostasis
and cancer growth (metastasis).10
Because physiological oxygen concentrations
are critical for regulating a multitude of cell
culture processes, atmospheric oxygen levels
can create unintended side effects, such as
reactive oxygen species (ROS) at higher oxygen
concentrations.
ROS affect cellular processes by damaging DNA,
modifying protein synthesis and function, and
causing cell membrane instability.11
Cell cultures grown in atmospheric oxygen
express a stress response gene signature which
is different than cells cultured in physiological
oxygen.

Consequently, using these cells for downstream cell culture experiments may have
unpredictable results. Culturing cells at
physiological oxygen levels brings cellular
metabolism and homeostasis to a much closer
in vivo level and activates key factors, such as
HIF, which has been shown to promote cell
adaptation and survival.
HIF in turn has a multitude of effects that allow
cells to grow faster, live longer, stay healthier and
have a more normal gene expression profile.12
In atmospheric oxygen, HIF is produced in low
or undetectable numbers. Here, excess oxygen
leads to detrimental cellular consequences, such
as oxidative damage and upregulation of stress
proteins.

In vitro Fertilization
With an increasing amount of research citing the
benefits of culturing cells at non-atmospheric
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