Al-Ani, A. et al. Oxygenation in cell culture: Critical parameters for reproducibility are routinely not reported. PLOS ONE 13, e0204269, https://doi.org/10.1371/journal.pone.0204269 (2018).
Google Scholar
Wittenberg, B. A. & Wittenberg, B. J. Transport of oxygen in muscle. Annu. Rev. Physiol. 51, 857–878, https://doi.org/10.1146/annurev.ph.51.030189.004233 (1989).
Google Scholar
Muoio, V., Persson, P. B. & Sendeski, M. M. The neurovascular unit – concept review. Acta Physiologica 210, 790–798, https://doi.org/10.1111/apha.12250 (2014).
Google Scholar
Klein, S. G. et al. A prevalent neglect of environmental control in mammalian cell culture calls for best practices. Nat. Biomed. Eng. 5, 787–792, https://doi.org/10.1038/s41551-021-00775-0 (2021).
Google Scholar
Jensen, F. B. Red blood cell pH, the Bohr effect, and other oxygenation‐linked phenomena in blood O2 and CO2 transport. Acta Physiologica Scandinavica 182, 215–227 (2004).
Google Scholar
López-Barneo, J., Pardal, R. & Ortega-Sáenz, P. Cellular mechanism of oxygen sensing. Annu. Rev. Physiol. 63, 259–287 (2001).
Google Scholar
Ausländer, D. et al. A synthetic multifunctional mammalian pH sensor and CO2 transgene-control device. Mol. Cell 55, 397–408, https://doi.org/10.1016/j.molcel.2014.06.007 (2014).
Google Scholar
Tao, J.-H., Barbi, J. & Pan, F. Hypoxia-inducible factors in T lymphocyte differentiation and function. A review in the theme: cellular responses to hypoxia. Am. J. Physiol.-Cell Physiol. 309, C580–C589 (2015).
Google Scholar
Ruan, K., Song, G. & Ouyang, G. Role of hypoxia in the hallmarks of human cancer. J. Cell. Biochem. 107, 1053–1062 (2009).
Google Scholar
White, K. A., Grillo-Hill, B. K. & Barber, D. L. Cancer cell behaviors mediated by dysregulated pH dynamics at a glance. J. Cell Sci. 130, 663–669 (2017).
Google Scholar
Kondo, A. et al. Extracellular acidic pH activates the sterol regulatory element-binding protein 2 to promote tumor progression. Cell Rep. 18, 2228–2242 (2017).
Google Scholar
Laurent-Emmanuel Monfoulet, P. B. et al. The pH in the microenvironment of human mesenchymal stem cells is a critical factor for optimal osteogenesis in tissue-engineered constructs. Tissue Eng. Part A 20, 1827–1840, https://doi.org/10.1089/ten.tea.2013.0500 (2014).
Google Scholar
Kikuchi, R. et al. Hypercapnia accelerates adipogenesis: a novel role of high CO2 in exacerbating obesity. Am. J. Respiratory Cell Mol. Biol. 57, 570–580 (2017).
Google Scholar
Packer, L. & Fuehr, K. Low oxygen concentration extends the lifespan of cultured human diploid cells. Nature 267, 423–425 (1977).
Google Scholar
Ast, T. & Mootha, V. K. Oxygen and mammalian cell culture: are we repeating the experiment of Dr. Ox? Nat. Metab. 1, 858–860 (2019).
Google Scholar
Semenza, G. L. Hypoxia-inducible factors in physiology and medicine. Cell 148, 399–408, https://doi.org/10.1016/j.cell.2012.01.021 (2012).
Google Scholar
Wang, G. L., Jiang, B.-H., Rue, E. A. & Semenza, G. L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. 92, 5510–5514 (1995).
Google Scholar
Semenza, G. L., Nejfelt, M. K., Chi, S. M. & Antonarakis, S. E. Hypoxia-inducible nuclear factors bind to an enhancer element located 3’to the human erythropoietin gene. Proc. Natl. Acad. Sci. 88, 5680–5684 (1991).
Google Scholar
Jang, Y. Y. & Sharkis, S. J. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110, 3056–3063, https://doi.org/10.1182/blood-2007-05-087759 (2007).
Google Scholar
Tsai, C.-C. et al. Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST. Blood, J. Am. Soc. Hematol. 117, 459–469 (2011).
Google Scholar
Gao, L. et al. Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells. Sci. Rep. 6, 1–13 (2016).
DiStefano, T. et al. Accelerated and improved differentiation of retinal organoids from pluripotent stem cells in rotating-wall vessel bioreactors. Stem Cell Rep. 10, 300–313 (2018).
Google Scholar
Li, M. & Izpisua Belmonte, J. C. Organoids—preclinical models of human disease. N. Engl. J. Med. 380, 569–579 (2019).
Google Scholar
Miyazaki, T. et al. Laminin E8 fragments support efficient adhesion and expansion of dissociated human pluripotent stem cells. Nat. Commun. 3, 1–11 (2012).
Nagaoka, M., Si-Tayeb, K., Akaike, T. & Duncan, S. A. Culture of human pluripotent stem cells using completely defined conditions on a recombinant E-cadherin substratum. BMC Developmental Biol. 10, 1–12 (2010).
Laperle, A. et al. α-5 laminin synthesized by human pluripotent stem cells promotes self-renewal. Stem Cell Rep. 5, 195–206 (2015).
Google Scholar
Chen, G. et al. Chemically defined conditions for human iPSC derivation and culture. Nat. Methods 8, 424–429 (2011).
Google Scholar
Pera, M. F. et al. Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J. Cell Sci. 117, 1269–1280 (2004).
Google Scholar
Kim, N., Minami, N., Yamada, M. & Imai, H. Immobilized pH in culture reveals an optimal condition for somatic cell reprogramming and differentiation of pluripotent stem cells. Reprod. Med. Biol. 16, 58–66 (2017).
Google Scholar
Li, M. & Belmonte, J. C. I. Deconstructing the pluripotency gene regulatory network. Nat. Cell Biol. 20, 382–392 (2018).
Google Scholar
Donovan, P. J. & Gearhart, J. The end of the beginning for pluripotent stem cells. Nature 414, 92–97, https://doi.org/10.1038/35102154 (2001).
Google Scholar
Zakrzewski, W., Dobrzyński, M., Szymonowicz, M. & Rybak, Z. Stem cells: past, present, and future. Stem Cell Res. Ther. 10, 68–68, https://doi.org/10.1186/s13287-019-1165-5 (2019).
Google Scholar
Chan, S. W., Rizwan, M. & Yim, E. K. F. Emerging methods for enhancing pluripotent stem cell expansion. Front. Cell Dev Biol 8, 70 https://doi.org/10.3389/fcell.2020.00070 (2020).
Kropp, C., Massai, D. & Zweigerdt, R. Progress and challenges in large-scale expansion of human pluripotent stem cells. Process Biochem. 59, 244–254, https://doi.org/10.1016/j.procbio.2016.09.032 (2017).
Google Scholar
Eagle, H. Buffer combinations for mammalian cell culture. Science 174, 500–503 (1971).
Google Scholar
Balin, A. K., Goodman, D. B., Rasmussen, H. & Cristofalo, V. J. Atmospheric stability in cell culture vessels. vitro 12, 687–692 (1976).
Google Scholar
Michl, J., Park, K. C. & Swietach, P. Evidence-based guidelines for controlling pH in mammalian live-cell culture systems. Commun. Biol. 2, 144, https://doi.org/10.1038/s42003-019-0393-7 (2019).
Google Scholar
Vallejos, J. R., Brorson, K. A., Moreira, A. R. & Rao, G. Dissolved oxygen and pH profile evolution after cryovial thaw and repeated cell passaging in a T-75 flask. Biotechnol. Bioeng. 105, 1040–1047 (2010).
Google Scholar
Pradhan, K., Pant, T. & Gadgil, M. In situ pH maintenance for mammalian cell cultures in shake flasks and tissue culture flasks. Biotechnol. Prog. 28, 1605–1610 (2012).
Google Scholar
Naciri, M., Kuystermans, D. & Al-Rubeai, M. Monitoring pH and dissolved oxygen in mammalian cell culture using optical sensors. Cytotechnology 57, 245–250 (2008).
Google Scholar
Papkovsky, D. B. Methods in optical oxygen sensing: protocols and critical analyses. Methods Enzymol. 381, 715–735, https://doi.org/10.1016/s0076-6879(04)81046-2 (2004).
Google Scholar
Kieninger, J. et al. Sensor access to the cellular microenvironment using the sensing cell culture flask. Biosensors 8, 44 (2018).
Ellert, A. & Grebe, A. Process optimization made easy: design of experiments with multi-bioreactor system BIOSTAT® Qplus. Nat. Methods 8, i–ii, https://doi.org/10.1038/nmeth.f.340 (2011).
Google Scholar
Wittmann, C., Kim, H. M., John, G. & Heinzle, E. Characterization and application of an optical sensor for quantification of dissolved O2 in shake-flasks. Biotechnol. Lett. 25, 377–380 (2003).
Google Scholar
Barrett, T. A., Wu, A., Zhang, H., Levy, M. S. & Lye, G. J. Microwell engineering characterization for mammalian cell culture process development. Biotechnol. Bioeng. 105, 260–275, https://doi.org/10.1002/bit.22531 (2010).
Google Scholar
Wenger, R. H., Kurtcuoglu, V., Scholz, C. C., Marti, H. H. & Hoogewijs, D. Frequently asked questions in hypoxia research. Hypoxia (Auckl., N. Z.) 3, 35–43, https://doi.org/10.2147/HP.S92198 (2015).
Google Scholar
Blaszczak, W., Tan, Z. & Swietach, P. Cost-effective real-time metabolic profiling of cancer cell lines for plate-based assays. Chemosensors 9, 139 (2021).
Google Scholar
Jose, C., Bellance, N. & Rossignol, R. Choosing between glycolysis and oxidative phosphorylation: a tumor’s dilemma? Biochimica et. Biophysica Acta (BBA)-Bioenerg. 1807, 552–561 (2011).
Google Scholar
Zheng, J. Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation. Oncol. Lett. 4, 1151–1157 (2012).
Google Scholar
Gu, W. et al. Glycolytic metabolism plays a functional role in regulating human pluripotent stem cell state. Cell Stem Cell 19, 476–490 (2016).
Google Scholar
Hopkins, E., Sanvictores, T. & Sharma, S. Acid Base Balance. [Updated 2021 Sep 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Available from: http://creativecommons.org/licenses/by/4.0/.
Aoi, W. & Marunaka, Y. Importance of pH homeostasis in metabolic health and diseases: crucial role of membrane proton transport. BioMed. Res. Int. 2014, 598986–598986, https://doi.org/10.1155/2014/598986 (2014).
Google Scholar
Brandenburg, M. A. & Dire, D. J. Comparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosis. Ann. Emerg. Med. 31, 459–465 (1998).
Google Scholar
Street, D., Bangsbo, J. & Juel, C. Interstitial pH in human skeletal muscle during and after dynamic graded exercise. J. Physiol. 537, 993–998 (2001).
Google Scholar
Good, N. E. et al. Hydrogen ion buffers for biological research. Biochemistry 5, 467–477 (1966).
Google Scholar
Kreü, S., Jazrawi, A., Miller, J., Baigi, A. & Chew, M. Alkalosis in critically ill patients with severe sepsis and septic Shock. PloS one 12, e0168563–e0168563, https://doi.org/10.1371/journal.pone.0168563 (2017).
Google Scholar
Fessler, M. B. CO2 as a potential obesogen: a gas that will stick to your ribs. Am. J. Respir. Cell Mol. Biol. 57, 499–500 (2017).
Duarte, C. M., Jaremko, Ł. & Jaremko, M. Hypothesis: potentially systemic impacts of elevated CO2 on the human proteome and health. Front. Public Health 8, 645 (2020).
Van Der Sanden, B., Dhobb, M., Berger, F. & Wion, D. Optimizing stem cell culture. J. Cell. Biochem. 111, 801–807 (2010).
Google Scholar
Kim, N. pH variation impacts molecular pathways associated with somatic cell reprogramming and differentiation of pluripotent stem cells. Reprod. Med. Biol. 20, 20–26 (2021).
Google Scholar
McBrian, M. A. et al. Histone acetylation regulates intracellular pH. Mol. Cell 49, 310–321 (2013).
Google Scholar
Zhang, C., Du, L., Pang, K. & Wu, X. Differentiation of human embryonic stem cells into corneal epithelial progenitor cells under defined conditions. PLOS ONE 12, e0183303, https://doi.org/10.1371/journal.pone.0183303 (2017).
Google Scholar
Yoshida, Y., Takahashi, K., Okita, K., Ichisaka, T. & Yamanaka, S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5, 237–241 (2009).
Google Scholar
Farzana Hakim, T. K. et al. High oxygen condition facilitates the differentiation of mouse and human. Annu. Rev. Cell Developmental Biol. 15, 551–578 (2001).
Ben-David, U. et al. Genetic and transcriptional evolution alters cancer cell line drug response. Nature 560, 325–330 (2018).
Google Scholar
Klein, S. G. et al. Toward best practices for controlling mammalian cell culture environments. Front. Cell Dev. Biol. https://doi.org/10.3389/fcell.2022.788808 (in press).
Young, E. W. & Beebe, D. J. Fundamentals of microfluidic cell culture in controlled microenvironments. Chem. Soc. Rev. 39, 1036–1048 (2010).
Google Scholar
Shi, J. et al. Current progress in long-term and continuous cell metabolite detection using microfluidics. TrAC Trends Anal. Chem. 117, 263–279 (2019).
Google Scholar
Koenig, L. et al. Production of human induced pluripotent stem cell-derived cortical neurospheres in the DASbox® mini bioreactor system. Application Note 364, 1–12 (2018).
Kumar, G. S., Kumar, B. K. & Mishra, M. K. Mitigation of voltage unbalances and sags with phase-jumps in grid connected wind generation. in IET Conference on Renewable Power Generation (RPG 2011), 2011, pp. 1–6, https://doi.org/10.1049/cp.2011.0176 (2011).
Klein, S. G. et al. In situ monitoring reveals cellular environmental instabilities in human pluripotent stem cell culture, Dryad, Dataset, https://doi.org/10.5061/dryad.41ns1rnd9 (2021).

