Cells are the basic structural and functional unit of all organisms. Without them, drug development would be stuck in the bad old days before antibiotics. Researchers need squillions of these membrane-bound bundles of molecules to develop new medicines and to make sure they’re safe. If you’ve worked in or around biopharma, you’ve likely heard the term “cell line” before. Every phase of drug discovery and development hinges on cell lines. This week and next, we’ll take a look at them: their origins and uses.
Terms of the Week: Cell Culture and Cell Line
Cell culture is the process by which cells are grown under controlled conditions outside their usual “habitat,”—be it rat, insect, or human body. To create a cell culture, scientists start with a bit of tissue and break apart its cells with enzymes. The cells go into a flat plastic flask of growth medium—a concoction of nutrients such as amino acids, carbohydrates, salts, vitamins, and minerals. Depending on the type of cell, the growth medium may also contain growth factors and hormones. The flask then goes into an incubator set close to body temperature—37 degrees Celsius.
Scientists call the cells that develop from the initial isolation and growth phase primary culture cells. After they’ve multiplied to cover the entire bottom of the flask, they’re ready for transfer to a bigger container. At this point, they’re referred to as a cell line. Most cell lines are “adherent,” which means they attach themselves to a solid surface such as the bottom of the flask. In contrast, suspension cultures can grow in the entire volume of medium. Once established, a cell line can be produced in quantity or frozen for later use.
The Birth of Human Cell Lines
Researchers have been establishing cell lines for about a century. American Type Culture Collection (ATCC; Manassas, VA), a nonprofit organization which collects and distributes cell lines, was established in 1925. Some species, such as rodents, give rise to cell lines relatively easily. With others, the process is much more trial-and-error. Dr. George Gey of Johns Hopkins University (Baltimore, MD) produced the first human cell lines in 1951. An oncologist, Gey tried to accomplish this by isolating cells from his patients’ tumor biopsies. Most of these attempts failed—until the cervical cancer biopsy of Henrietta Lacks. Her cells proved to be tremendously amenable to growing in the lab, and established one of the most widely used cell lines within biomedical research today: HeLa cells.
Because HeLa cells came from a cancer biopsy, they’re “immortal,”—capable of living endlessly in the lab. Cell lines from healthy tissues can divide only a limited number of times in culture before they die.
To persist indefinitely, cell lines must be “transformed” into immortal cells. Scientists infect the cells with certain viruses, which disrupt genes that regulate their growth. Cells from tumors and those enhanced with viruses possess characteristics that differentiate them from healthy cells. Researchers who want to study normal cells use a different method to prolong their viability. They add a gene that codes for “human telomerase reverse transcriptase.” This gene provides cells with an enzyme that lengthens telomeres. These short sequences of DNA appear at the end of all chromosomes. Extending their length extends the life of the cell.
Biomanufacturing for the 21st Century
The Minute Confines of Drug Discovery Research
The biotech applications of cell lines are seemingly infinite. For example, oncologists examine cancer cell lines to understand the mechanisms of a particular cancer or screen potential drug candidates. Non-cancerous cell lines may be used in drug safety testing. To study a virus in the lab, scientists must find an “infectible” cell line to see how it interacts with its host. For example, scientists studying a respiratory virus may use A549 cells, a common lung cell line. Finally, researchers use cells to make proteins for study, using recombinant DNA technology to transfer the gene into the cell. Chinese hamster ovary (CHO) cells and human embryonic kidney cells (HEK293) provide particularly rich grounds for producing human proteins.
Super Cell Lines: iPSCs
Induced pluripotent stem cells (iPSCs) are the rock stars of cell culture. “Pluripotent” means that these cells possess the amazing potential to become any adult human cell type. They begin as humble and highly accessible adult human skin cells. Activating certain genes in the lab turns these humdrum cells into biopharmaceutical magic. iPSCs have become invaluable to some research efforts. In Alzheimer’s disease, for example, it’s impossible to get biopsies of patients’ brains. Now, researchers can convert skin cells from an Alzheimer’s patient into an iPSC and then coax them into becoming brain cells. Because they have the same genetics as Alzheimer’s patients, scientists can use them to model the disease in the lab.
Next week, we’ll turn our focus to cell lines used in biomanufacturing. We’ll explore the tried and true CHO cells and take a look at a new cell line that may offer some new advantages.