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Semi-Annual Review of Lifeline Products Featured in 2021

2021 has been a monumental year for science with the landmark approvals of not one, but two COVID-19 vaccines in the US with many other candidates in the clinical pipeline. The speed at which we went from mRNA sequence selection to preclinical evaluation was unprecedented and highlights the extraordinary ecosystem of technologies available to scientists today that are helping overcome unforeseen global challenges like COVID-19. Here at Lifeline® Cell Technology, we are proud to be part of the scientific community providing researchers with the tools necessary to drive innovation and discovery. As we close out the year, let’s take a look back at some of the publications featured on the blog in our semi-annual review.

Research Featuring Lifeline’s Skin Cells

Ultraviolet radiation (UVR), especially ultraviolet B (UVB), exposure is one of the leading causes of skin cancers like melanoma. Maintenance of normal circadian clock rhythms and melanin production each play a vital role in protection against solar UVB-induced DNA damage but a link between these two mechanisms is not well understood. Lifeline’s human melanocytes cultured in DermaLife Ma Melanocyte Complete Medium were used in a study by Sarkar and Colleagues to investigate the relationship between the circadian clock gene BMAL1 and melanogenesis and how disruptions of the circadian clock rhythm can lead to the development of melanoma. Both the in vivo and in vitro studies showed that BMAL-1 directly regulates melanogenesis through the microphthalmia-associated transcription factor (MITF) protein. Melanocytes induced to overexpress BMAL1 and exposed to UV-B had increased levels of MITF and melanin synthesis, which increased cell survival compared to control cells. The positive effect of the BMAL1-MITF axis on melanogenesis could serve as a potential therapeutic target to enhance melanin synthesis, thereby increasing protection against UVB-induced damage in future sunscreen development strategies.

Research Featuring Lifeline’s Pulmonary Artery Cells

COPD is a chronic lung condition where inflammation reduces airflow into the lungs that can result in hypoxia-induced pulmonary vascular remodeling (PVR), which is characterized by pulmonary artery endothelial cell (PAEC) dysfunction, uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs), hypertrophy, and collagen accumulation in the vascular walls. Building on previously published research, Lui and Colleagues focused on identifying how the endogenous sulfur oxide (SO2)/ aspartic aminotransferase 1 (AAT1) pathway drives the pathologies associated with COPD-induced hypoxic PVR. The researchers used in vitro Transwell co-cultures of Lifeline’s human PASMCs and PAECs to confirm their initial findings determined from animal studies. Transwell cultures were established with HPASMCs seeded in the lower compartment and HPAECs transfected with AAT1 shRNA to knockdown SO2 levels in the upper compartment to look at gene expression changes caused by SO2 suppression. The authors found increased PAEC inflammation, PASMC proliferation, and collagen accumulation caused, which led them to conclude that PAEC-derived SO2 protects against the development of PVR pathologies, and further analysis revealed that SO2 works by modulating intracellular p50. Therefore, SO2 could be a potential treatment for hypoxic PVR in cardiopulmonary diseases like COPD.

Research Featuring Lifeline’s Endometrial Epithelial Cells

The incidence of Type 1 endometrial cancer (EC) has increased over the past two decades due to an increased prevalence of obesity – a known positive correlation between body mass index (BMI) and EC incidence exists. The study by Lin and Colleagues provided evidence that the paracrine molecule plasminogen activator inhibitor-1 (PAI-1) secreted by adipose tissue-derived stem cells (ASCs) can alter the transcriptional programs of endometrial epithelial cells (EECs) and potentiate them towards tumorigenesis. The researchers found elevated levels of PAI-1 in EECs isolated from obese individuals compared to Lifeline’s normal primary ECCs. Increased PAI-1 promoted ASC infiltration into the endometrial space and downregulated TGF-β /SMAD4 signaling in EECS, which led to JAC repression in vitro. These genes play roles in anti-tumor responses; therefore, their suppression is thought to promote epithelial tumorigenesis and obesity-driven endometrial cancer. The pro-tumorigenic paracrine effects of PAI-1 occur at a higher frequency in obese individuals, because of an increased concentration of adipose tissue (and concomitant increase in PAI-1 secretion) in proximity to the uterus.

Research Featuring Lifeline’s Cell Culture Products

The rapid spread of COVID-19 during the global pandemic has led many scientists to look at repurposing existing FDA-approved drugs to find effective treatments for acute lung injury caused by SARS-CoV-2 infection faster than conventional drug discovery. Kost-Alimova and Colleagues screened a library of FDA-approved compounds to find one capable of reducing levels of mucin-1 (MUC1) protein as a treatment for SARS-CoV-2-induced acute lung injury (ALI) based on the knowledge that MUC1 levels predict the development of ALI and acute respiratory distress syndrome (ARDS) and correlate with poor clinical outcomes. An immortalized kidney epithelial cell line (P cells) and human kidney epithelial cells isolated from a patient with MUC1+ kidney disease, both cultured in Lifeline’s RenaLife Renal Basal Medium supplemented with RenaLife LifeFactors were used in their high-content immunofluorescence (IF) imaging screen. MUC1 protein levels and viable cell numbers were used as success metrics to identify candidate molecules. Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK), first approved for the treatment of chronic immune thrombocytopenia (ITP), was identified here as a repurposing candidate for the treatment of ALI. The scope of work is consistent with data presented by other groups implicating SYK-mediated processes in ARDS and lung injury and provides a strong rationale to pursue clinical trials to test R788 treatment in patients suffering from acute COVID-19-related lung injury.

Research Featuring Lifeline’s Aortic Endothelial Cells

Tobacco smoke is a leading contributor to cardiovascular disease (CVD) development. Next-generation tobacco and nicotine products (NGPs) such as e-cigarettes with reduced levels of chemical toxicants are rising in popularity but the differential effect of e-cigarette smoke on CVD processes like monocyte adhesion and vascular endothelial cell dysfunction compared to tobacco smoke is not clear. Makwana and Colleagues designed a new in vitro model using the BioFlux system that has microfluidic channels mimicking in vivo vascular flow to investigate the effects of e-cigarette smoke and tobacco cigarettes on CVD development. Lifeline’s Primary Human Aortic Endothelial cells (HAECs), grown in VascuLife VEGF Endothelial Cell Culture Medium with VEGF LifeFactors, were used to establish monolayers in the BioFlux microfluidic channels. Endothelial cells were treated for 24h with tobacco or e-cigarette smoke conditioned media prior to the monocyte adhesion assay. The researchers found that both tobacco and e-cigarette smoke increases monocyte adhesion to the to HAECs but that e-cigarette smoke did so to a much lesser degree. Tobacco smoke-induced adhesion was preferentially mediated by the ICAM-1-CD11b pathway while the results suggest an alternate molecular mechanism of action driving monocyte adhesion for e-cigarette smoke. This study successfully validated the BioFlux microfluidics system that, in combination with the THP-1 monocyte adhesion assay, is better in vivo model to study the tobacco risk continuum that could be implemented by other labs to provide standardization to enable collaborative and global studies in the future.

We want to wish everyone a safe and happy end to 2021 and look forward to continuing our coverage of new and interesting topics across a spectrum of life sciences research with you on the blog in 2022. Be sure to sign up for our newsletter so you don’t miss any new promotions.

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