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Induced pluripotent stem (iPS) cells are generated from somatic cells by the forced expression of a defined set of pluripotency-associated transcription factors. Human iPS cells can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for extraembryonic tissues.

Each of these studies looks at a different cell type: MEF, Adipose-derived stem cells, liver bud, and hiPSC-EC in ischemic retinal conditions.

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’)

If these studies are of interest to you, have you considered signing up for our HypoxEU international forum on oxygenation and biology on September 16th? You can sign up to the virtual event here: https://zoom.us/meeting/register/tJEsdO2hrjMrGNH8_ov6k7NZnEqfIEpIBimg