Smooth Muscle and Endothelial Cells: Their Critical Role in Blood Flow and Vascular Homeostasis

Large Vessel Endothelial and Smooth Muscle Cells

The vessels that make up the circulatory system are multi-layered complex organs. Arteries carry oxygenated blood away from the heart to the tissues of the body and veins carry de-oxygenated blood back toward the heart. Capillaries are small blood vessels that lie between arteries and veins and facilitate exchange of oxygen, carbon dioxide, and other factors. Blood vessels are composed of multiple cell types. The outer layer consists mostly of connective tissue, which helps adhere vessels to tissues within the body. The middle layer is where smooth muscle cells reside, which control the constriction and dilation of the vessel and therefore, the blood flow.

Finally, the innermost layer consists of a single layer of endothelial cells and other supporting cells. The endothelial cells have a critical role in vascular homeostasis. In particular, they form the barrier between the blood and the internal environment. They also are able to respond and regulate inflammatory responses, blood clotting, and angiogenesis, or the formation of new vessels. Importantly, endothelial cell dysfunction can contribute to vascular diseases, such as atherosclerosis.

Lifeline® Endothelial Cells in the Literature

Polyimide is a structural polymer commonly used in medical device development. However, information about its biocompatibility with human endothelial cells has been limited. Therefore, in a study from 2015, Starr et al. tested the biocompatibility of a newly developed polyimide blood pressure transducer with endothelial cells.

They first treated human capillary and microvascular endothelial cells (SV-HCECs) with three polyimide extracts (thermosetting 4,4’-oxydiphenylene-pyromellitimide, thermosetting biphenyldianhydride/1,4 phenylenediamine, and a proprietary thermoplastic adhesive) to assess the effects on mitochondrial stress. To do this, they monitored changes in mitochondrial membrane potential. They found that, compared to latex rubber, which induced mitochondrial stress, the polyimide extracts did not significantly alter mitochondrial homeostasis.

Next, using markers of apoptosis (annexin V and propidium iodide staining), they found that the polyimide extracts tested did not induce significant SV-HCEC apoptosis or cell death, suggesting the materials used in the experimental transducer were not cytotoxic.

Finally, using Lifeline® primary human aortic endothelial cells, the authors directly tested the biocompatibility of the completed blood pressure transducer. Using calcein-AM staining (activated by live cells to a green fluorescent calcein), they demonstrated that the experimental blood pressure sensor did not alter cell viability or morphology. Although in vivo studies will still have to be performed, this study illustrates that this polyimide-based blood pressure transducer is not cytotoxic to human endothelial cells, which are the main cell type the device will encounter during a medical procedure.

Here at Lifeline®, we love to share the new ways that researchers around the world are using our cells to develop new experimental systems. In particular, the diverse ways our cells can be used in culture illustrate their versatility.

In a study from 2016, Zhang and colleagues used a co-culture system of Lifeline® human coronary artery smooth muscle cells (SMCs) and Lifeline® human coronary artery endothelial cells to study how low levels of laminar shear stress could induce SMC phenotypic switching from a contractile phenotype to a synthetic phenotype. Their study implicated the alteration of heterotypic gap junctions between SMCs and endothelial cells in this process. Here we will highlight the co-culture system used in this study, but to learn more about the findings of this paper, see our previous blog Smooth Muscle Cells: Contractile Controllers.

The authors established a co-culture of Lifeline® coronary artery SMCs and endothelial cells using a Transwell system. Transwells are inserts that sit within a cell culture dish and have a porous membrane. Cells can be seeded on the upper and/or lower side of this membrane and medium is added to both sides. The cells on either side of the membrane are therefore allowed to interact with each other while remaining physically separate. In this study, SMCs were seeded on the top of the membrane and endothelial cells were seeded on the underside of the membrane (both seeded at 5 x 10⁵ cells).

Interestingly, the authors found that the endothelial cells and the SMCs send extensions through the pores of the Transwell membrane to form heterotypic gap junctions. Of note, this system also allows for the top and bottom compartments to be exposed to different conditions or medium. The authors here developed a way to expose the endothelial cells to shear stress by flowing medium through the lower chamber, while the SMCs in the upper chamber were maintained under static conditions.

Therefore, this orientation mimics that in a blood vessel, with the endothelial cells exposed to the vessel lumen and blood flow, and the SMCs on the outside the endothelial layer. Importantly, this co-culture system, and others like it, can be used to study the interactions between two cell types in a way that mimics the tissue in vivo.

The catalog of Lifeline® human vascular SMCs and endothelial cells includes:

• Aortic SMCs
• Aortic endothelial cells
• Coronary SMCs
• Coronary endothelial cells
• Microvascular endothelial cells
• Iliac artery endothelial cells
• Pulmonary SMCs
• Pulmonary endothelial cells
• Umbilical vein endothelial cells

Every other week we highlight research that uses Lifeline® cells in different ways. Keep checking back to see what’s new!