Smooth muscle cells or myocytes are ubiquitously present in the body. They maintain vasomotor tone in the aorta, airway diameter in the lungs, and milk ejection in the mammary gland. They can alter their physiology in accordance with the external stimuli. However, abnormal organization or cell proliferation is implicated in diseases such as asthma, atherosclerosis, hypertension, etc. Several medications even target these myocytes, like bronchodilators that relax the inflammation in airway smooth muscles. However, many of its aspects remain in the shadows.
Smooth Muscle Cells
These are essential for various body functions. They differ from skeletal myocytes in their involuntary control by the nervous system and contractile ability.
Structure: They possess a fusiform shape, that is, they are thick in the middle region and taper at the ends, along with an elongated nucleus. Actin (thin) and myosin (thick) filaments confer the contractility to them. An array of these filaments is absent in smooth myocytes, thus giving a non-striated appearance, unlike skeletal myocytes. Electron micrographs exhibit dense bodies which contain the proteins responsible for contraction. Myocytes interact with each other via adherents or gap junctions for a uniform contraction across the tissue. The cell arrangement in a multi-layer structure allows optimal contractility. However, any change in the alignment can give rise to a pathological condition. For example, myocytes assume spheroid arrangement in uterine fibroids.
Function and Location: Smooth Myocytes are mostly present at the walls of hollow organs such as lungs, blood vessels, urinary tract, and gastrointestinal systems. They are responsible for regulating the tissue tone and synthesizing the extracellular matrix (ECM) proteins. Through these functions, they regulate blood pressure, pupil dilation, food movement, urine flow, and bronchiole volume. Their mechanisms of action include the increase of cytoplasmic calcium under the influence of stimuli via two manners- calcium influx from plasma membrane channels and calcium release from the sarcoplasmic reticulum. Calcium binds to calmodulin and further activates myosin light chain kinase (MLCK), which induces the contraction of actin-myosin elements.
Isolation of Smooth Muscle Cells
Enzymatic and explant methods are two ways to isolate smooth myocytes. Both methods require the removal of connective tissue to obtain vessels. The residual tissue is cut into smaller pieces after scraping off the endothelium along its length.
Enzymatic Method: This method requires the addition of the solution of collagenase and then elastase enzymes to the tissue. In a few hours, cells appear on the flasks. Digestion of the tissue follows the centrifugation and culturing of cells.
Explant Method: It entails placing the tissue pieces with their luminal side towards the substrate after the removal of endothelium. After ensuring the attachment of tissue pieces to the culture dish, more media is added gently. After a few weeks, a sufficient density of myocytes is visible on the cell culture dish, allowing the removal of tissue pieces and following a normal culture process.
Characterization: The cells can now be characterized by morphology and markers such as α-SM actin, myosin heavy chain, desmin, SM22α, etc. The absence of endothelial cells is noticeable by negative staining for von Willebrand factor (vWF) and acetylated low-density lipoproteins (LDL). Since a specific marker for these cells does not exist, the evaluation of a range of markers provides adequate verification.
Culture of Smooth Muscle Cells
Smooth myocytes assume two distinct phenotypes- contractile and synthetic. The synthetic phenotype has low contractility along with high proliferation, rough endoplasmic reticulum, and ECM synthesis compared to the contractile phenotype. Supplementation of cell culture medium with basic fibroblast growth factor and insulin preserves the contractile phenotype. In contrast, the culture dish requires coating with collagen type I. The synthetic phenotype exhibits a hill and valley appearance in the culture. In the in vitro culture, the contractile force of cells exceeds the cell-substrate interactions, leading to the formation of a three-dimensional structure resembling a hill and valley pattern.
Primary Lung Smooth Muscle Cells: Maintaining Respiratory Health
Smooth myocytes extend from the trachea all the way up to the bronchioles. Their key function is to regulate the diameter of bronchioles and airway resistance. According to the developmental model, they arise from neural crest cells. Myocytes have been involved in the pathology of chronic lung diseases. They participate in airway inflammation, wall thickness, and hyper-responsiveness. Studies have suggested that inflammation drives the upregulation of certain receptors and kinases, leading to increased cellular sensitivity. Lung diseases also demonstrate the increased number and size of myocytes. The increase in cell proliferation as a repair response to injury could contribute to cell number increase. Additionally, they also drive inflammation by expressing adhesion molecules and releasing chemokines and cytokines.
Primary Aortic Smooth Muscle Cells: Supporting Vascular Integrity
The smooth myocytes are the prominent cell type in the tunica media layer of the aorta. The myocytes present in the ascending aorta and aortic arch originate from the neural crest cells, whereas those in the descending aorta belong to the somatic mesoderm. They provide structural and functional support as well as respond or adapt to mechanical and environmental cues by transitioning between contractile and synthetic phenotypes. Factors like inflammation, oxidative stress, injury, etc., can trigger the apoptosis of these myocytes. It also impairs the ability to repair and regenerate ECM, which confers elasticity to the aorta. Additionally, it also causes a shift into synthetic phenotype and the secretion of ECM-degrading proteolytic enzymes. The degraded matrix promotes the migration of myocytes, leading to apoptosis. Any dysfunction can weaken the aortic wall, causing dilatation and resulting in aortic aneurysms.
Human Mammary Smooth Muscle Cells: Role in Breast Cancer
Myoepithelial cells are specialized smooth myocytes or muscle cells of the mammary gland. Its contractile feature aids in milk ejection during lactation. They also contribute to the mammary gland remodeling. Moreover, studies have suggested their role in tissue polarity and enhancing cell survival. In response to oxytocin, they contract via actin-myosin proteins and calcium-dependent pathways. Dysregulation of human mammary smooth muscle cells causes breast cancer progression. Breast carcinoma demonstrates changes in tissue polarity, loss of myoepithelial cells, and structural collapse of the tissue. The expression of ECM proteins, angiogenesis inhibitors, and ECM accumulation by these cells might contribute to the non-invasiveness of breast cancer. Thus, myoepithelial cells could be the key to breast carcinoma treatment.
The Final Outlook
The rising mortality due to lung disease, cardiovascular disorders, and breast cancer has prompted the discovery of an absolute cure. Smooth myocytes or muscle cells have emerged as a therapeutic target for drug development. They play a pivotal role in the structure and function of a tissue. Their dysfunction has been associated with several diseases. The research continues to understand the signaling pathways of myocytes in normal and diseased tissues. Kosheeka provides smooth myocytes or muscle cells to accelerate your research and drug discovery process. Their team of expert scientists ensures the quality of the product by following GMP-compliant protocols and performing high-throughput screening to promote hassle-free research.
FAQs
Q: What are smooth myocytes or muscle cells?
They are spindle-shaped cells containing contractile proteins actin and myosin. Their key function is to maintain the tone of the tissue and synthesize the extracellular matrix, thus supporting the structure and function of the tissue.
Q: What are the different phenotypes of smooth myocytes?
They have two phenotypes- contractile and synthetic. As compared to the contractile phenotype, the synthetic phenotype is less contractile but has a higher proliferation rate and rough endoplasmic reticulum, along with increased ECM synthesis.
Q: What is hill and valley morphology?
Synthetic smooth myocytes often form a three-dimensional structure in the cell culture, which resembles a hill and valley, thus giving the same name to the growth pattern.
Q: What disorder or diseases are smooth myocytes implicated in?
They are involved with asthma, atherosclerosis, aortic aneurysms, breast cancer, etc.
