Studying how changes in oxygen levels affect iPSC faith

For MEF cells, results showed:

• Improved efficiency for both mouse and human cells.
• Cells carrying Nanog-GFP-Ires-Puro cassette and four or three transcription factors (Oct3/4, Klf4, +/− c-Myc) were introduced with retroviral vectors.
• 5%/1% O2.
• Hypoxia significantly increased the number of four-factor transduced MEFs but not mock transduced MEFs.
• Hypoxia enhanced the expression of reprogramming-related genes.
• Hypoxia enhances the reprogramming of MEFs without STO feeder cells.

(Yoshida et al 2009, Cell Stem Cell: ‘Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells’)

For adipose-derived stem cells, results showed:

• Cells were transduced with individual pMX-retroviral vectors coding for mouse Oct4, Sox2, Klf4, L-Myc, and DsRed and kept in 5% O2.
• Accelerated generation of iPSCs (from 10 days to 6 days).

(Shimada et al 2011, BBRC: ‘Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia‘)

For liver bud cells, results showed:

• In 10% O2 hepatocyte differentiation in liver buds is promoted.
• In mild 10% O2 is most efficient in reducing TGFb expression and so is a favourable environment for hepatocytic differentiation.

(Ayabe et al 2018, Stem Cell Reports: ‘Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling’)

For hiPSC-EC in ischemic retinal conditions, results showed:

• In 1% O2 hiPSC-ECs show increased proliferation compared to mature human retina ECs.
• In hypoxia hiPSC-EC show incorporation into regenerating retinal vessels, indicative of marked degree of reparative angiogenesis.
• SDF1a/CXCR4 activation is apparent in hypoxic cells.

(Cho et al 2020, JCI: ‘iPSC-derived endothelial cell response to hypoxia via SDF1a/CXCR4 axis facilitates incorporation to revascularize ischemic retina’)