CSC niche

There are several connections between hypoxia and control of normal stem cell biology. For example, hematopoietic stem cells (HSCs) are enriched in hypoxic regions of bone [133], expansion of HSCs ex vivo is more efficient under hypoxic conditions [134], and neurosphere formation is also enhanced at 3% O2 [135]. In addition, it has been suggested that CSCs exist in a hypoxic environment and that hypoxia stimulates expansion of CSCs, as reviewed in [16]. For example, the local microenvironment of the stem cell niche may influence the ability of CSCs to... 

In this chapter, we review the current definition of CSCs and several methods that can be used to prospectively identify putative CSCs and study their niche requirement. Then we present traditional view of chemoresistance and review newly emerged evidence that CSCs may be naturally resistant to therapy. Finally, novel potential therapeutic strategies targeting CSCs and their niches are introduced. 

One of the major questions raised by CSC hypothesis is whether or not current therapies are in fact targeting the right cells. As discussed above, it has been speculated that CSCs have the ability to avoid or resist current cancer therapies, although this has yet to be definitively proven in the clinical setting. In addition, CSCs may play an important role in tumor metastasis and dormancy. So, the idea that cancers could be effectively treated by selectively targeting CSCs and their microenviromnental niche, which contributes to self-renewal of these cells, has attracted tremendous clinical interest [81]. 

In light of the central role of niche in maintaining quiescence and self-renewal of CSCs, strategies for reduction of the SC population must take into account the... 

HSCs need hypoxic niche to proted them from oxidative stress because reactive oxygen spedes induce p38-MAPK-mediated proliferation leading to HSC exhaustion [105]. Some CSCs may also be concealed in hypoxic microenvironments, which are common in solid tumors. Given that hypoxia seems to be important in maintaining CSCs, this provides an opportunity for tumor-selective therapy. Hypoxia-inducible factor 1 (HIF-1) is stabilized under hypoxic conditions and promotes survival of cancer cells in hypoxic niches, so several strategies to inactivate HIF-1 are currently under investigation at the preclinical level [106,107]. 

Many clinical trials of drugs targeting bulk cancer cells or CSCs and their niches, although exciting and effective in preclinical trials, have not yielded positive results in patients. There are two possible reasons to explain this discrepancy. First, the preclinical models may be inappropriate. Numerous agents have shown very promising activity in animal models but have minimal clinical activity. One of the main reasons for this failure is the use of... 

The planer type SOFCs with ASC and MSC are selected for operation at temperature range of 400 to 850 °C. ESC and Cathode Supported Cell (CSC) are also concerned in our scope of research for consideration of their special characteristics and fimctions as well as niche benefits, such as the anti-redox capability of ECS and cost reduction of CSC. 

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