15 cell culture facts: Things about cell culture you might not know

Cell culture is the backbone of modern science, driving breakthroughs in life sciences and biomedicine since the early 20th century. Even if you work with cells daily, there are likely a few facts about cell culture you didn’t know. Here are 15 fascinating cell culture facts:

#1: Plastic can contaminate cell cultures

Microorganisms, like viruses, bacteria, and mycoplasma, are not the only cell contaminants. Plasticizers eluted from plastic instruments and substances present in water can also contaminate cells in culture.^1,2 These chemical contaminants can affect the behavior of the cells, potentially introducing variability in your downstream assays.

#2: Frog nerve fibers were the first successfully cultured cells

In 1907, American zoologist and experimental embryologist Ross Granville Harrison was the first to grow animal cells outside the body. He adapted the “hanging drop” method from bacteriology for use with tissue culture and successfully cultured frog nerve cells in clotted frog lymph.³

The method R.G. Harrison described in 1907 is now well adapted and has become a crucial tool for the advancement of life science research. However, the principle of cell culture dates back to 1885, when German scientist William Roux cultured medullary plate of a chicken embryo in a warm saline solution for 13 days.⁴

#3: Cultured meat is no longer science fiction

Cultured meat, also known as lab-grown or cultivated meat, is an innovative meat production approach involving growing animal tissue in vitro using tissue engineering techniques. The manufacturing process starts with stem cells, which are grown into skeletal muscle, fat, and connective tissues that make up meat.⁵

The development of cultured meat has gained significant attention because of its potential to address various challenges associated with conventional meat production, such as environmental impact, animal welfare concerns, and food security issues.⁶ The United States, Brazil, Colombia, Argentina, and various European countries have been discussing the prospects of cultured meat, highlighting its potential as a global innovation in the food industry.⁷

#4: It is possible to grow stem cells in space

In microgravity, stem cells naturally develop into three-dimensional (3D) tissue-like structures that more closely resemble in vivo settings.⁸ Experiments in space confirmed the feasibility of growing stem cells in microgravity, which developed organ-like liver, bone, and cartilage structures.⁸ This achievement has paved the way for commercialization of 3D tissue organoids grown in outer space. Pharmaceutical and biotech companies could use space-grown organoids for drug testing, and transplant recipients may benefit from these tissues when organ donations are scarce.

#5: HeLa cells, the first “immortal” cell line, were established without consent

Obtained from Henrietta Lacks, HeLa cells paved the way for cell-based research. Cells from a tumor biopsy of her cervical cancer taken in 1951 were established as the first human cell line without Henrietta’s knowledge. Her family did not learn of their use until 1975, sparking debates about patient rights and privacy.¹⁰ It wasn’t until 2013 that an agreement was reached between the NIH and Lacks’ descendants, setting a landmark precedent in research ethics.¹¹

Over the past decades, HeLa cells have been used for groundbreaking research, such as developing a polio vaccine, understanding HIV, and studying the causes of cervical cancer.¹²

#6: Cell culture is a tool to resurrect woolly mammoth

Cell culture has become a vital tool in the effort to resurrect the woolly mammoth. Researchers are exploring advanced embryological techniques like cloning to revive extinct species, such as the woolly mammoth.¹³ Genome editing methods are being investigated to alter the DNA of close relatives of the woolly mammoth to match its genome. Approximately 60 elephant genes are planned to be edited into the woolly mammoth counterpart.¹⁴

However, the process of using genome engineering to recreate a woolly mammoth from existing elephants has proven challenging and necessitates the incorporation of a significant number of deletion and insertion variants in the editing process.¹⁵

#7: The first modern cell culture medium was created more than 60 years ago

Medium 199 was developed by J.F. Morgan in 1950 and was one of the first synthetic media used to grow mammalian cells in culture.¹⁶ The idea of designing a chemically defined medium without animal components made Medium 199 an ideal medium for vaccine production. It also allowed large-scale manufacturing of vaccines for the polio vaccination campaign in 1955.¹⁷ Nine years after Morgan, scientist Harry Eagle developed the minimum essential medium (MEM), which contained a mixture of glucose, salts, amino acids, and vitamins.¹⁸

#8: Components of culture medium can interact with each other and influence cultured cells

Trying to optimize your cell culture medium? Consider that individual components of the medium don’t act alone. Components can interact, and their effects on cells are not always predictable. This is particularly important when replacing animal sera in culture media.^19,20 You might need to use mathematical algorithms to optimize the combination of multiple compounds and to establish the best conditions for cell growth.^19,20

#9: Researchers can grow mini-organs in the lab by culturing organoids

Organoids have become a valuable tool in biology and medicine, allowing mini-organs to be created in laboratory settings. These mini-organs replicate the structural and physiological functions of real organs, providing a platform for studying organogenesis, disease modeling, and drug development.²¹

• Mini-brains: These organoids resemble the complexity of the human brain and provide a detailed view of how neurons form and grow.²²
• Mini-livers: Liver organoids have been created that can potentially serve as an alternative organ source for transplantation. They can also be used to study liver biology and disease.²³
• Mini-hearts: Heart organoids can help in studying cardiac development and disease.²⁴
• Mini-kidneys: Kidney organoids can be used to study the development and progression of kidney diseases.²⁵
• Mammary and salivary gland organoids: These organoids can help in understanding the development and diseases of the mammary and salivary glands.²⁶

#10: Bioprinting organs and tissues started in 2003

Thomas Boland, a bioengineer at the University of Texas, was working with an inkjet printer when he noticed that ink droplets were about the same size as human cells. This observation prompted him to fill an ink cartridge with living bovine cells, nutrients, and other bio-compatible substances to create “bioink” that was capable of printing living tissues.²⁷ Since then, scientists have successfully used 3D bioprinting technology to generate tissues, including multilayered skin, bone, heart, and tracheal splints.²⁸

#11: Phenol red can compromise your cell culture results

Phenol red is a pH indicator that provides the typical color of cell culture media. Changes in the color of phenol red-containing culture media give a quick insight into cell growth and overall cell culture health; nonetheless, the dye can also interfere with your assay results.²⁹ If you work with estrogen-sensitive cell lines, you might want to switch to a phenol red-free media for your cell culture.³⁰

#12: FBS supplements can alter extracellular vesicle research data

Fetal bovine serum (FBS) provides the growth factors and nutrients necessary for a nourishing ecosystem in cell culture. However, if you are working with extracellular vesicles (EVs), you should reconsider the use of FBS in cell culture. Recent studies reported that the protein and growth factor aggregates from FBS can influence the EVs isolation.³¹

#13: Supercooling can enhance preservation of human organs

A recent article in Nature Biotechnology reported a new method for supercooling and storing human livers at -4ºC without ice formation. This approach could extend the ex vivo life of organs from 12 hours to 27 hours, which would expand access to liver transplantation.³²

#14: AI is here to make your cell culture work easier

The recent wave of advancements in artificial intelligence (AI) reached the cell culture field as well. If you’re tired of the hideous workload of cell culture, AI tools could make your life easier by automating certain aspects of cell culture.³³ Recently, deep learning has successfully contributed to applications such as fluorescent staining prediction, cell type differentiation, bacterial resistance, and super-resolution microscopy.³⁴

#15: Cell therapy is witnessing its most pivotal time

In recent years, cell therapy has transformed translational medicine. Recent clinical and commercial successes include the use of CAR-T cells to treat cancer and stem cells to treat myocardial infarction and diabetes.³⁵ These therapies have overcome regulatory hurdles and become commercially available, resulting in growing public recognition and excitement. As of March 2024, 36 cell and gene therapy products have been approved by the US FDA, with over 3,700 investigational therapies in clinical and preclinical development globally.^36,37

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