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Top 9 Cytocentric Publications 2021

This was a big year for Cytocentric cell culture research. Our customers alone published over 300 journal articles, but Cytocentric practices extend well beyond those. After reviewing hundreds of reviews and reports from journals and authors from all over the world, we chose nine as the best at putting the needs of cultured cells first in 2021.


Klein, Alsolami, Steckbauer, Arossa, Parry, Ramos Mandujano, Alsayegh, Izpisua Belmonte, Li and Duarte.

A prevalent neglect of environmental control in mammalian cell culture calls for best practices.

This ground-breaking review made our list because it calls for a widespread and permanent change in how routine cell culture is done: with careful attention to environmental controls for better scientific reproducibility. Please read and absorb every word of this landmark paper. We couldn’t agree more.

Journal/Nat Biomed Eng. 2021. 10.1038/s41551-021-00775-0.


Szojka, Li, Sopcak, Ma, Kunze, Mulet-Sierra, Adeeb, Westover, Jomha and Adesida.

Mechano-Hypoxia Conditioning of Engineered Human Meniscus.

Alex Szojka and co-authors have established an environment for culturing meniscus cells that can control not only the ambient oxygen levels to more physiologic levels, but also apply mechanical stresses to the tissues in culture. The combination of these factors has led to better development of engineered human meniscus tissue in vitro. This is inherently cytocentric.

Journal/Front Bioeng Biotechnol. 2021. 10.3389/fbioe.2021.739438.


Barreto-Duran, Mejia-Cruz, Jaramillo-Garcia, Leal-Garcia, Barreto-Prieto and Rodriguez-Pardo.

3D Multicellular Spheroid for the Study of Human Hematopoietic Stem Cells: Synergistic Effect Between Oxygen Levels, Mesenchymal Stromal Cells and Endothelial Cells.

Combining HSC with MSC and EC into spheroids was better for HSC, and even at lower physiologic oxygen levels, resulted in spheroids that were not necrotic in the center. This is cytocentric because it is a more physiologic culture system than flat plastic and room air, and a big step forward for 3D cell culture.

Journal/Journal of Blood Medicine. 2021.


Dumas, Villacreces, Guitart, El-Habhab, Massara, Mansier, Bidet, Martineau, Fernandez, Leguay, Pigneux, Vigon, Pasquet and Desplat.

Dual Inhibition of FLT3 and AXL by Gilteritinib Overcomes Hematopoietic Niche-Driven Resistance Mechanisms in FLT3-ITD Acute Myeloid Leukemia.

These authors worked to reduce the in vitro/ in vivo disconnection by creating a far more physiologically relevant in vitro environment. They also used drug concentrations that were realistic for the true exposure of the cells in vivo. Quite simply, all toxicology work should be done taking these factors into consideration.

Journal/Clin Cancer Res. 2021. 10.1158/1078-0432.CCR-20-3114


Coyle, Barrs, Richards, Ladd, Menick and Mei.

Targeting HIF-alpha for robust prevascularization of human cardiac organoids.

This publication caught our eye because the authors made clever usage of HIF-1a, an oxygen regulated master controller, to help create a more physiologically relevant model for cardiac tissue in vitro. Performing experiments with cell lines on flat plastic has not translated to better human treatments. Work like this, with human cells in more in vivo-like structures, will.

Journal/J Tissue Eng Regen Med. 2021. 10.1002/term.3165.


Mas-Bargues and Borras.

Importance of stem cell culture conditions for their derived extracellular vesicles therapeutic effect.

This review paper was Cytocentric in that (1) the authors pulled together many different sources that looked at the true conditions of MSC cultured for production of EVs and (2) the authors communicated their findings well. They presented a compelling case that controlling the oxygen levels of MSC to physiologic levels can improve their growth in culture, change the cargo of the EVs produced, and change the effect of EV treatment on other tissues.

Journal/Free Radic Biol Med. 2021. 10.1016/j.freeradbiomed.2021.03.028.


Imperio, Lye, Mughis, Hamada, Bloise, Lye and Matthews.

Hypoxia alters the expression of ACE2 and TMPRSS2 SARS-CoV-2 cell entry mediators in hCMEC/D3 brain endothelial cells.

Almost every person on this planet has been affected by the COVID-19 pandemic. Much of the research on ACE2 and TMPRSS2, molecules which are essential for COVID viral infection, have been done in room air oxygen. This is neither physiologically relevant for normal tissues, nor pathologically relevant for a disease that causes hypoxia. This paper looked at lower oxygen levels, which is Cytocentric and absolutely critical for us to find new treatments.

Journal/Microvasc Res. 2021. 10.1016/j.mvr.2021.104232.


Wiley and Campisi.

The metabolic roots of senescence: mechanisms and opportunities for intervention.

As the median age of humanity increases, our understanding of the fundamental role that metabolism plays in controlling cell fate becomes more important. Senescence is not only important for anti-aging research, but also for all in vitro models using primary, non-immortalized human cells. This review paper made our Cytocentric list because of how the authors clearly communicated the effect of non-physiologic concentrations of not only oxygen, but also glucose on the senescence of cells in traditional culture.

Journal/Nature Metabolism. 2021. 10.1038/s42255-021-00483-8.


Nikolits, Nebel, Egger, Kress and Kasper.

Towards Physiologic Culture Approaches to Improve Standard Cultivation of Mesenchymal Stem Cells.

The emphasis on controlling the initial cell culture conditions with the goal of more physiologic MSC culture is what made this paper stand out from the crowd. Cytocentric cell culture is all about control of cell conditions. The authors here not only share the importance of physiologic oxygen and cell culture media, but they also take some time to consider the practical aspects of working with physiologic oxygen levels in the laboratory.

Journal/Cells. 2021. 10.3390/cells10040886.

These papers are not the only publications that illustrated Cytocentric Principles this year, but they represent the gathering movement toward more relevant and reproducible conditions for cells in vitro. The way that Science is done changes only slowly, but we look forward to a future where Cytocentric cell culture brings new treatments to humans faster, cheaper, and with less animal suffering.