It’s time for our mid-year review, how quickly it has passed! In the first half of 2021, we covered a lot of research and industry insight on COVID-19 and SARS-CoV-2 infection, reflective of the deep societal and public health impact it has had globally. Researchers utilized Lifeline® cells to further their understanding of SARS-CoV-2 as well as a variety of other diseases such as cancer, diabetes, and psoriasis. This highlights how robust in vitro cellular models can provide deep insight into disease mechanisms that can be utilized to develop better, more effective therapeutics. Join us as we recap the last six months and review all of the scientific successes that have been achieved with Lifeline’s cell and media products.
Influenza and coronaviruses like SARS-CoV-2 utilize the lung and airway cells of the respiratory tract as the main entry point into the body. Gard and Colleagues utilized Lifeline’s Human Bronchial/Tracheal Epithelial Cells (HBTECs) to develop a more physiologically relevant, high throughput in vitro model with hopes that it could expedite timelines to test lifesaving therapeutics. Lifeline’s primary HBTECs were cultured in BronchiaLife media and then differentiated using the HBTEC-ALI differentiation media to create a pseudostratified epithelium at an air-liquid interface (ALI) to recreate the in vivo respiratory barrier. The PREDICT96-ALI platform’s permissiveness and response to viral infections was evaluated as well as its efficacy to test anti-viral therapeutic agents. The researchers found viral infectivity kinetics and anti-viral responses to be comparable to patient results in the clinic, demonstrating the potential of the PREDICT96-ALI airway model as a pre-clinical tool to evaluate potential therapies for combating respiratory infections including SARS-CoV-2 in an efficient, robust, and high-throughput manner.
During cancer progression, tumor cells develop the ability to metastasize, invading surrounding normal tissues and moving through tissue boundaries to form new, distal tumor growths far from the primary tumor site. We looked at two publications earlier this year that focused on the role of the endothelial barrier in tumor metastasis in breast and prostate cancer.
During breast cancer metastasis, previous research suggests that secreted nucleoside diphosphate kinase A and B (NDPK) from breast cancer-derived extracellular vesicles (EVs) promotes angiogenesis and pro-metastatic events. Duan and Colleagues investigated the role of EV-associated NDPK in remodeling the endothelial barrier to promote metastasis through enhancement of purinergic signaling using Lifeline’s Human Umbilical Vein Endothelial Cells – HUVECs. High levels of both adenosine and ATP in the tumor microenvironment compared to healthy tissues increases NDPK activity and appear to activate endothelial cells in support of tumor cell migration through increased vascular permeabilization and angiogenesis.
Pan and Colleagues utilized an in vitro coculture model system with Lifeline’s HUVECs and the prostate tumor cell line PC-3M to study the underlying molecular mechanisms and biological processes triggered by tumor cell adhesion to the endothelium. Transcriptomics analysis revealed that PRKAA2 mRNA expression was significantly higher in cocultured HUVECs/PC-3M than HUVECs alone. This PRKAA2 expression was found to be regulated by the miRNA miR-124-3p leading the authors to speculate that modulating the “miR-124-3p/PRKAA2” pathway activated by tumor cell attachment plays a pivotal role in tumor–endothelium interactions and may be a target for therapeutics.
Diabetic retinopathy (DR) is a debilitating eye condition, which can result in vision loss and blindness in people with diabetes. A publication by Ibrahim and Colleagues used Lifeline’s Normal Human CD14+ Monocyte Cells as an in vitro retinal endothelium model to determine the underlying molecular mechanism causing DR. High glucose levels in diabetes was found to activate the 12/15-LO pathway in the retinal endothelial cells, which increased ICAM-1 expression on their surface. This in turn promoted monocyte adhesion to the endothelium and disruption of the blood-retinal barrier enabling the monocytes to invade the retinal space and causing the retinal capillary damage observed in DR. Because the interaction between monocytes and the endothelium is a key early event in DR progression, targeting the 12/15-LO pathway in endothelial cells may facilitate the development of more precisely targeted therapeutic strategies to treat the disease.
Psoriasis is a chronic inflammatory skin disease that causes red, itchy scaly skin patches to develop thought to be triggered by dysfunctional inflammatory responses in response to skin barrier defects. Previous research implicated phospholipase C epsilon (PLCε) and the cytokine IL-22 in different types of skin inflammation. Zhang and Colleagues used Lifeline’s primary human epidermal keratinocytes to investigate the molecular connection between PLCε and IL-22 in mediating the inflammatory in response to the disruption of the skin barrier. The authors found that PLCε deficiency reduces inflammation cascade after barrier disruption but IL-22 expression remained unchanged. This suggests that IL-22 acts upstream of PLCε in keratinocytes to modulate its activity and together IL-22/PLCε signaling potentially involves in barrier-related diseases like psoriasis.
Using high-quality cells to model in vivo behavior is a powerful research technique and has provided a wealth of understanding into disease onset and progression, as well as offering a tool to test novel therapeutics. We, at Lifeline Cell Technology, are pleased to be able to provide scientists with the tools necessary to conduct their research and look forward to reviewing more research successes here on the blog.