Semi-Annual Review of Lifeline Products
2023 has been an exceptional year for scientific advancements, marked by significant progress in the field of COVID-19 research and the availability of multiple vaccines. The remarkable speed at which mRNA sequencing and preclinical evaluations have taken place demonstrates the vast array of technological tools at the disposal of scientists today, enabling them to overcome unforeseen global challenges such as COVID-19. Lifeline® Cell Technology takes great pride in being an integral part of the scientific community, providing researchers with the necessary tools to drive innovation and discovery. As we move into the second half of 2023, let us take a moment to reflect on some of the noteworthy publications featured on our blog during our semi-annual review.
Research Featuring Lifeline’s Skin Cells
Ultraviolet radiation (UVR), particularly ultraviolet B (UVB) exposure, remains one of the primary causes of skin cancers, including melanoma. The relationship between maintaining normal circadian clock rhythms and melanin production plays a crucial role in protecting against solar UVB-induced DNA damage. Lifeline’s human melanocytes, cultured in DermaLife Ma Melanocyte Complete Medium, were utilized in a study by Sarkar and Colleagues to explore the connection between the circadian clock gene BMAL1 and melanogenesis. Their research aimed to understand how disruptions in the circadian clock rhythm can lead to melanoma development. Both in vivo and in vitro studies revealed that BMAL1 directly regulates melanogenesis through the microphthalmia-associated transcription factor (MITF) protein. Melanocytes that overexpressed BMAL1 and were exposed to UV-B demonstrated increased levels of MITF and melanin synthesis, resulting in enhanced cell survival compared to control cells. These findings highlight the potential therapeutic targeting of the BMAL1-MITF axis to enhance melanin synthesis and augment protection against UVB-induced damage, thus contributing to future strategies in sunscreen development.
Research Featuring Lifeline’s Pulmonary Artery Cells
Chronic obstructive pulmonary disease (COPD) is a lung condition characterized by reduced airflow due to inflammation, which can lead to hypoxia-induced pulmonary vascular remodeling (PVR). PVR is marked by dysfunction in pulmonary artery endothelial cells (PAECs), uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs), hypertrophy, and collagen accumulation in the vascular walls. Building on previous research, Lui and Colleagues focused on unraveling how the endogenous sulfur oxide (SO2)/aspartic aminotransferase 1 (AAT1) pathway contributes to the pathologies associated with COPD-induced hypoxic PVR. In their study, Lifeline’s human PASMCs and PAECs were co-cultured in Transwell systems to validate their initial findings from animal studies. The Transwell co-cultures consisted of HPASMCs seeded in the lower compartment and HPAECs transfected with AAT1 shRNA to suppress SO2 levels in the upper compartment. This setup allowed the researchers to examine the gene expression changes resulting from SO2 suppression. The study demonstrated that suppressed SO2 levels led to increased PAEC inflammation, PASMC proliferation, and collagen accumulation. These findings indicate that PAEC-derived SO2 plays a protective role against the development of PVR pathologies and further analysis revealed its modulation of intracellular p50. Thus, SO2 could be a potential treatment for hypoxic PVR in cardiopulmonary diseases such as COPD.
Research Featuring Lifeline’s Endometrial Epithelial Cells
The incidence of Type 1 endometrial cancer (EC) has been on the rise over the past two decades, primarily due to the increased prevalence of obesity. It is well-established that there exists a positive correlation between body mass index (BMI) and EC incidence. Lin and Colleagues conducted a study providing 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 drive them toward tumorigenesis. The researchers discovered elevated levels of PAI-1 in EECs isolated from obese individuals compared to Lifeline’s normal primary ECCs. Increased PAI-1 facilitated ASC infiltration into the endometrial space and downregulated TGF-β/SMAD4 signaling in EECs, resulting in the repression of JAC in vitro. These findings suggest that the suppression of anti-tumor response genes may promote epithelial tumorigenesis in the context of obesity-driven endometrial cancer. The pro-tumorigenic paracrine effects of PAI-1 occur more frequently in obese individuals due to the increased concentration of adipose tissue (and the corresponding increase in PAI-1 secretion) in close proximity to the uterus.
Research Featuring Lifeline’s Cell Culture Products
The rapid spread of COVID-19 during the global pandemic has prompted scientists to explore the repurposing of FDA-approved drugs for the effective treatment of acute lung injury caused by SARS-CoV-2 infection. Kost-Alimova and colleagues conducted a screening of a library of FDA-approved compounds to identify molecules capable of reducing mucin-1 (MUC1) protein levels, with the goal of treating SARS-CoV-2-induced acute lung injury (ALI). MUC1 protein levels have been shown to predict the development of ALI and correlate with poor clinical outcomes. In their study, an immortalized kidney epithelial cell line (P cells) and human kidney epithelial cells, isolated from a patient with MUC1+ kidney disease, were cultured in Lifeline’s RenaLife Renal Basal Medium supplemented with RenaLife LifeFactors. These cells were used in a high-content immunofluorescence (IF) imaging screen, where MUC1 protein levels and viable cell numbers served as success metrics to identify candidate molecules. The study identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia (ITP), as a potential candidate for repurposing in the treatment of ALI. The findings align with existing data implicating SYK-mediated processes in ARDS and lung injury, providing a strong rationale for further 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 remains a leading contributor to the development of cardiovascular disease (CVD). Next-generation tobacco and nicotine products (NGPs), such as e-cigarettes with reduced levels of chemical toxicants, have gained popularity. However, the differential effects of e-cigarette smoke and tobacco smoke on CVD processes, such as monocyte adhesion and vascular endothelial cell dysfunction, are not yet fully understood. Makwana and colleagues designed an innovative in vitro model using the BioFlux system, which incorporates microfluidic channels that mimic in vivo vascular flow. The aim was to investigate the effects of e-cigarette smoke and tobacco cigarettes on CVD development. Lifeline’s Primary Human Aortic Endothelial cells (HAECs), cultured in VascuLife VEGF Endothelial Cell Culture Medium with VEGF LifeFactors, were used to establish monolayers in the BioFlux microfluidic channels. The HAECs were treated with tobacco or e-cigarette smoke conditioned media for 24 hours before conducting the monocyte adhesion assay. The researchers found that both tobacco smoke and e-cigarette smoke increased monocyte adhesion to the HAECs, although e-cigarette smoke had a lesser effect. Tobacco smoke-induced adhesion was primarily mediated by the ICAM-1-CD11b pathway, whereas e-cigarette smoke appeared to employ an alternate molecular mechanism for driving monocyte adhesion. This study successfully validated the BioFlux microfluidics system, which, in combination with the THP-1 monocyte adhesion assay, provides a better in vivo model for studying the tobacco risk continuum. It is hoped that other labs will adopt this system to enable collaborative and global studies in the future.
We look forward to continuing our coverage of new and interesting topics across a spectrum of life sciences research with you. Be sure to sign up for our newsletter so you don’t miss any new promotions.
Photo by Edward Jenner: https://www.pexels.com/photo/man-doing-a-sample-test-in-the-laboratory-4033148/