The human body can effectively overcome infections and various conditions thanks to a selective barrier within our blood vessels, composed of endothelial cells. These cells are crucial for maintaining smooth blood flow, but different pathologies can disrupt their function. For instance, cancer cells alter endothelial cells, leading to angiogenesis, which facilitates an increased supply of nutrients to the tumor.
Recognizing the vital role of Human Primary Endothelial Cells helps us understand their importance in biology. In this blog, we will explore various aspects of endothelial cells, shedding light on their functions and the implications of their dysfunction.
What are Endothelial Cells?
We will try to understand these cells using analogies. So, you can imagine your body as a vast city. There are several roads laid down to provide the essential goods in your body. The 'roads' we are talking about are blood vessels. The asphalt on this road is made up of the endothelial cells. These tiny but mighty cells form a barrier between your blood and the rest of your body.
They do much more than just lining blood vessels; they play a crucial role in four bodily functions. These four functions include:
- Filtration of all biofluids, including blood.
- Blood vessel size regulation.
- Contribute to the hemostasis of the biofluid.
- Transport of various substances throughout the body.
Okay, as we did a quick refresh of the endothelial cells and their functions, let us look at where do endothelial cells come from?
Where Do Endothelial Cells Come From?
Traditionally, scientists have preferred using immortalized endothelial cells of various origins for their research. These cells are obtained from various sources including umbilical cords, heart, and other organ tissues. To immortalize the primary human endothelial cells researchers use the expression of hTERT (human Telomerase Reverse Transcriptase). But with the recent FDA modernization act that has removed the mandate for animal testing, the primary cells are preferred over the traditional cells.
All the human primary endothelial cells are obtained from different human organs, including umbilical cords, heart, and other tissues. These cells are preferred because they behave like they do in the body. They carry the same physiological activity with the same metabolic activities. The only downside of these human primary endothelial cells is a short lifespan in the lab. In addition, there is a possibility that these cells can have high variability when using endothelial cells that vary from one person to another.
Overcoming the Challenges of Human Primary Endothelial Cells
To overcome the challenges posed by the human primary cells, scientists have also turned to revolutionary technique "induced pluripotent stem cells." In this technique, scientists are able to create endothelial cells using the donors' skin or blood cells (Please note we cannot use RBCs). The scientists then express the Yamanaka factors to create stem cells then direct the differentiation of the cells towards endothelial cells.
These cells behave very similar to Primary Human Endothelial Cells. One contrasting feature is that because of the expression of Yamanaka factors, these cells can also move towards an oncogenic fate as well. Scientists are still trying to figure out how they can stop the oncogenic presence of the data.
Studying Endothelial Cells: A Closer Look
When we look at endothelial cells, we must be able to distinguish that what we are working with is actually the endothelial cells. In order to do so, we must know a few characterizing steps. Let's look at a few of the characteristic features:
- Morphology of the Cells: Human primary endothelial cells grow as a monolayer with a typical "cobblestone" pattern. These cells undergo division only when there is physical separation of the cells.
- Qualitative and Quantitative Cell Surface Marker Expression: Using FACS analysis, it is important to note that umbilical cord endothelial cells or any other type carry the cell surface markers CD31, CD34, CD144, and CD146.
- Protein Expression Analysis: Ensuring that the protein expression profile in the endothelial cells does not change is another crucial aspect. There are two methods available either check via protein labeling or do a western blot check.
- Gene Expression Analysis: It is a step that must correspond to the protein expression analysis as the mRNA will give rise to the protein of interest. Using RT-PCR accompanied with quantitative PCR to quantify mRNA levels of endothelial-specific genes.
Once we are done with all these checks, we know that the collection of cells in our in vitro plate are all human primary endothelial cells, maybe from the umbilical cord, aorta, or liver. We have established their presence in the in vitro culture.
Endothelial Cells: A Versatile Tool
The incredible properties of endothelial cells make them valuable for various physiological and pathological studies. These cells are not only limited to understanding the basic biology but are also being used in various therapeutic applications as well, including:
- Healing Wounds: When you get a cut, the endothelial cells come into action to help create new blood vessels. These new blood vessels also bring in healing cells to the wound, which accelerates the wound healing process. Scientists are exploring ways to use this property of endothelial cells to speed up wound healing in chronic conditions like diabetic ulcers.
- Organ-on-chip Models: To understand how umbilical cord endothelial cells control the communication between the fetus and mother, researchers are using them on organ-model chips to understand what they need. Other than that, these models are also useful in high throughput drug screening, disease modeling, drug safety, and efficacy.
- Fighting Diseases: Many diseases, such as heart conditions, diabetes, or neurological diseases, affect blood vessels. By studying endothelial cells, scientists are starting to understand how these diseases develop. For example, the research published in a 2019 study reported that exosomes from human primary endothelial cells prevent neural injury.
- Drug Testing: Before a new drug is given to people, it was supposed to be tested on animals. But with the FDA modernization act 2.0 removing the mandate from animal testing, researchers are using primary human endothelial cells to study the effect of the drug. What is more interesting is it enables researchers to check the effect of drugs on multiple cell types in the lab. Meaning they can check what the drug will do to Umbilical Cord Endothelial Cells, cardiac cells, liver cells, and many more. These tests can reveal how the drug affects human cells.
Last Words
While the world of endothelial cells might sound complex, understanding these tiny cells is crucial for developing new therapies and improving human health. As research progresses, we can expect to see even more exciting discoveries and advancements in this field.
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