The academic world and the private research sector have shifted their focus from two-dimensional (2D) cell culture to the use of three-dimensional (3D) model systems, which have become increasingly important over the last two decades. 3D models – especially when using complex organoids – provide us with more relevant data, as cells in a 3D culture experience an environment that more closely resembles physiological conditions in the human body.
To study a specific organ or tissue, one needs to choose the cell type accordingly, e.g., using spheroids or organoids formed from cells of the lung can give us valuable data for studying lung diseases. It is well known that air pollutants such as diesel exhaust particles (DEPs) have negative effects on the health of our lungs and are a major public health problem. They are also thought to increase the risk of developing highly relevant lung diseases such as COPD or asthma.
Changes in epithelial cells mark the beginning of lung disease
Cultures of bronchial epithelial cells (BEC) are excellent for studying the development of lung disease in vitro. These cells form the natural lining of our lower airways. We know from previous research that these cells undergo specific changes when the lungs are damaged. One of these changes is the epithelial to mesenchymal transition (EMT), in which epithelial cells lose some of their properties while gaining mesenchymal properties. This is a rather drastic transition from a cellular perspective, as epithelial and mesenchymal cells are quite different and originate from different parts of the embryonic cotyledons.
Changes in BECs can be induced by hormones
Interestingly, EMT of BECs can be induced by exposing them to the hormone transforming growth factor-β1 (TGF-β1) [1]. This growth factor is also involved in the signaling pathway leading to EMT when exposed to DEPs [2]. Knowledge of the function of this key hormone allows us to study the effects of various drugs that interact with TGF-β1 on cells and their behavior.
3D BEC culture enables studies for the cure of COPD
If TGF-β1 is responsible for EMT, thereby causing the pathological phenotype in the lung, is it possible to block the effects of TGF-β1 and thereby prevent EMT? This important question was investigated by Zuo and colleagues [2]. It was shown that the use of a TGF-β1 neutralizing antibody that blocks TGF-β1 signaling also inhibits EMT. This means that the use of such an antibody or other drugs that interfere with this signaling pathway are interesting candidates for the development of cures for a variety of lung diseases or general improvement of lung function in patients.
There is so much more to discover
This is just one of many examples of how cell culture has provided us with new ideas for developing new treatments. Similar results would have been possible in an animal model but would have involved higher costs and more time. 3D cell culture can be used as a first step to evaluate the safety and efficacy of drugs before testing them in animal models.
Watch our step-by-step video on magnetic 3D Bioprinting of spheroids:
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References
[1] Borthwick LA, Gardner A, De Soyza A, Mann DA, Fisher AJ. Transforming Growth Factor-β1 (TGF-β1) Driven Epithelial to Mesenchymal Transition (EMT) is Accentuated by Tumour Necrosis Factor α (TNFα) via Crosstalk Between the SMAD and NF-κB Pathways. Cancer Microenviron. 2012 Apr;5(1):45-57. doi: 10.1007/s12307-011-0080-9. Epub 2011 Jul 27. PMID: 21792635; PMCID: PMC3343199.
[2] Zuo H, Trombetta-Lima M, Heijink IH, van der Veen CHTJ, Hesse L, Faber KN, Poppinga WJ, Maarsingh H, Nikolaev VO, Schmidt AM. A-Kinase Anchoring Proteins Diminish TGF-β1/Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition. Cells. 2020 Feb 3;9(2):356. doi: 10.3390/cells9020356. PMID: 32028718; PMCID: PMC7072527.
[3] Baarsma HA, Van der Veen CHTJ, Lobee D, Mones N, Oosterhout E, Cattani-Cavalieri I, Schmidt M. Epithelial 3D-spheroids as a tool to study air pollutant-induced lung pathology. SLAS Discov. 2022 Apr;27(3):185-190. doi: 10.1016/j.slasd.2022.02.001. Epub 2022 Feb 25. PMID: 35227934.
[4] Greiner Bio-One Magnetic 3D bioprinting of spheroids