Cell immortalization is a process that allows a population of cells to bypass the normal aging process and divide indefinitely. In multicellular organisms, most cells have a predetermined number of divisions they can undergo before they stop replicating. Immortalization confers the ability to proliferate for prolonged periods when grown in a laboratory setting, or in vitro.
This change can happen through naturally occurring mutations or be intentionally induced by scientists for experimental purposes. The resulting populations of immortalized cells are known as cell lines, which provide a continuous and consistent source of cells for scientific work. By overcoming the natural endpoint of a cell’s life, immortalization creates a unique biological tool.
The Finite Lifespan of Normal Cells
Most cells in the body have a built-in limitation on how many times they can divide, which acts as a natural barrier against uncontrolled growth. When cells approach this boundary, they enter a state called replicative senescence. In this phase, the cell remains alive and metabolically active but permanently ceases to divide.
This concept is quantified by the Hayflick limit, which describes the finite number of times a normal human cell population will divide, around 40 to 60 divisions. This process is marked by changes in the cell’s shape and an increase in size. Senescence serves as a protective measure, helping to prevent the propagation of older cells that may have accumulated damage over time.
The underlying mechanism for this cellular clock involves structures called telomeres. Telomeres are protective caps of repetitive DNA sequences at the ends of chromosomes. With each round of cell division, a small portion of the telomere is lost, causing them to shorten. This erosion acts as a molecular counter, signaling the cell to enter senescence when the telomeres become critically short to protect the genetic information.
Mechanisms of Cellular Immortalization
For cells to achieve immortality, they must overcome the natural barriers that enforce a finite lifespan. The primary obstacle is the shortening of telomeres, which cells can bypass by activating an enzyme called telomerase. The activation of telomerase allows for the rebuilding and maintenance of telomere length, effectively disarming the cellular clock that leads to senescence. In a laboratory, scientists can induce this by inserting the gene that codes for the human telomerase reverse transcriptase (hTERT) protein.
Beyond maintaining telomeres, cells must also circumvent the internal surveillance systems that regulate their division cycle. These systems, known as cell cycle checkpoints, are controlled by tumor suppressor genes like p53 and Rb. These genes act as brakes, halting cell division in response to stress or DNA damage. To immortalize cells, these braking mechanisms must be disabled.
This is often accomplished using specific viral genes, or oncogenes, that interfere with tumor suppressors. For instance, the large T-antigen from Simian Virus 40 (SV40) is a tool used to inactivate both p53 and Rb. Similarly, the E6 and E7 oncogenes from the human papillomavirus (HPV) can be used to achieve the same effect. Sometimes, a combination of activating telomerase and inactivating tumor suppressors is needed for successful immortalization.
Immortalization in Disease
The process of immortalization is not just a laboratory phenomenon; it is a feature of cancer. The ability of cells to replicate indefinitely allows tumors to form and grow. For a normal cell to transform into a cancerous one, bypassing the normal limits on cell division is a fundamental step.
Cancer cells achieve this sustained proliferation by employing the same mechanisms scientists use to create immortalized cell lines. Through genetic mutations, these cells reactivate the telomerase enzyme. This prevents their telomeres from shortening, granting them an unlimited replicative potential that allows them to divide far beyond the Hayflick limit.
In conjunction with telomere maintenance, cancer cells must also neutralize the body’s internal safety checks. Mutations frequently occur in tumor suppressor genes like p53 and Rb, disabling the pathways that would otherwise halt the division of abnormal cells. This inactivation of cellular brakes, combined with limitless division, enables the uncontrolled growth that allows a small group of cells to develop into a life-threatening mass.
Applications in Scientific Research
Immortalized cell lines are tools in biological and medical research, providing a stable and unending supply of cells for study. Their primary advantage is consistency; because they can be grown indefinitely, researchers can perform long-term experiments using the same cell line for comparable and reproducible results. This avoids the variability that comes with using primary cells, which must be repeatedly harvested from tissues.
These cell lines serve as models for investigating cellular processes and the progression of diseases like cancer and viral infections. They are also used in the development of new medical treatments. Pharmaceutical companies use immortalized cells for large-scale screening to test the effectiveness and potential toxicity of new drug compounds before they are considered for human trials.
Two famous examples highlight their impact. HeLa cells, the first human immortalized cell line, were derived from cervical cancer cells in 1951 and have been used in countless studies, including the development of the polio vaccine. HEK 293 cells are another widely used line, valued for their reliability in producing therapeutic proteins and for their application in gene therapy research.