HEK cells?

Ever wonder where human embryonic kidney (HEK) cells originate? Or why are they so commonly used as cell culture models? In this article, we will cover all aspects of HEK in detail, from the first experiments to isolate cell lines all the way to modern applications.

Where did the HEK cell line come from?

HEK cells were first isolated by Alex van der Eb in the Netherlands in the 1970s. Transforming HEK cells with adenovirus 5 DNA was Dr. Frank Graham's 293rd experiment, hence the nomenclature we use today: HEK-293. But the exact source of the fetal tissue from which HEK was isolated remains a mystery, but it is now believed that the cells came from aborted fetuses.

HEK-293FT (Qida Biology; Article number: CD0185) 

HEK-293(Qida Biology; Item number :CD0021)

What are the characteristics of HEK?

Heks have unusual ploidy and are considered heteroploidy: most chromosomes are represented by two or three copies, but a few have four. The line does not have a Y chromosome and is therefore genetically female. HEK is usually cultured as an adherent monolayer, although the derivatives have been adapted to grow in suspension. Among the many derivatives of HEK-293, the most commonly used strain expresses SV40 large T antigen and is therefore known as HEK-293T.

Given how far modern cell lines are from the original isolates, it is difficult to determine their true tissue origin. Initially, it was thought that HEK was a common cell type in the kidney, whether endothelial, epithelial, or fibroblast. However, Frank Graham found that HeKs exhibit many immature neuron-like features that are inconsistent with kidney cells (Shaw et al.). Since then, transcriptome studies of the cell line have determined that it is most likely of adrenal origin. (Anatomy: The adrenal glands are adjacent to the kidneys and are known to have some neuronal properties.) While HEKs may not be a great model for kidney cell biology, thankfully they have many other applications that are useful!

293T(Qida Biology; Article number: CD0025) 

293A (Qida Biology; Item number: CD0291)

How do you use HEK cells?

As one of the oldest cell lines in the research community, many cell research tools have been optimized specifically for HEK. These systems built around HEK offer the advantage of using cell lines, and we will highlight some of these applications here.

First, virus production

Heks are "packaging cells" for virus production because they express SV40 large T antigens. This allows them to replicate viral plasmids that have SV40 replication sources. To produce a virus, you just need to transfect "helper" plasmids (virus packaging machines) and viral plasmids containing genes of interest, and HEK will produce and package viral particles. The virions are then filtered to remove any unwanted material (HEK cells, etc.) and prepared for use in another cell or organism. The pipeline is used to transfect cell lines for basic scientific research as well as the production of clinical viral therapies.

Second, protein production

HEK is easily transfected in large quantities and produces high levels of recombinant protein. In the case of necessary recombinant proteins for clinical use, HEKs are derived from humans, so they eliminate non-human PTM (exclusion), which is the focus of other protein production systems such as yeast. HEK can also be grown in suspension, which allows the cells to better adapt to industrial amplification culture and serum-free growth, reducing production costs and maintaining the stability of production proteins.

3. Research applications

Because of their inherent characteristics, HEK cells may be particularly useful in two areas of research.

The tumorigenicity of HEK-293 cells makes it a candidate cell line model for cancer specific studies.

At the same time, membrane receptors and ion channels of HEK-293 cells are often expressed and studied exogenously in HEK, due to the consistent production of these proteins by cell lines and the relatively low expression of their natural channels.

Whatever your research question, HEK-293 is known for repeatable results. It is also widely available, which allows for a seamless transition of biological tools to other researchers using the cell line.

What happened to your HEK?

All cultured cell lines are susceptible to mycoplasma and bacterial contamination, and HEK is particularly susceptible to viral infection. Yes, your cells can catch a cold or worse! Once cell proliferation is slow or cell vacuoles suddenly appear, in addition to paying attention to your digestive operation, periodic detection of mycoplasma and bacterial slide detection is essential.

HEK-293T and its derivatives are immortal, but most cellular health degrades over time in culture. This could affect factors (gene expression, growth rate, etc.) that could skew the results. Therefore, it is important to keep the culture period short (less than 20 passes) to prevent these problems from cropping up. If your research does not allow this, HEK may be the cell line you are looking for, because as long as it does not contaminate and destroy, it has achieved "immortality" like hela.

Is HEK right for you?

If you are looking for human cell line models, HEK might be a good choice! Especially if your research interests include receptor biology, ion channels, or human protein preparations involving PTM. Why not choose HEK?

References

Shaw G., et al., Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells. FASEB J. (2002) (8):869-71. DOI: 10.1096/fj.01-0995fje

Tan, E., et al., HEK293 Cell Line as a Platform to Produce Recombinant Proteins and Viral Vectors. Front Bioeng Biotechnol. (2021)  (9) : 796991. DOI: 10.3389 / fbioe. 2021.796991