Primary cell isolation from tissues was the first step in the in vitro culture process. They enabled the examination of physiological processes outside of the body due to their unique tissue-specific features. Their limited lifespan, however, posed a significant challenge. In order to perform long-term investigations, it required frequent isolation from tissues. This spurred scientists to formulate media that support optimal cell growth and proliferation.
However, in 1951, a discovery dramatically transformed biomedical research. Scientists observed the indefinite proliferation of cells derived from a cervical cancer patient, naming them HeLa, after the patient’s initials. It essentially introduced the concept of immortality in the in vitro culture. Today, the culture of immortal cells has become a standard practice in in vitro research due to their many advantages.
 
Immortal Cells  

Cells normally have a restricted ability to proliferate; they only survive in culture for a predetermined period of time before senescence.  As a result, it is now common practice in the in vitro cultures to track the passage number in order to keep track of the number of cell divisions. 
In this context, Leonard Hayflick put forth the concept of the Hayflick limit, indicating the maximum number of divisions before senescence.
In 1948, Wilton R. Earle established the first continuous or immortal cell line, L929. It belonged to fibroblasts from a 100-day-old C3H/An mouse. They surpassed the Hayflick limit, which became the immortal cell definition. However, before they could gain prominence, the HeLa cell line achieved worldwide attention as the first human Immortal Cell Line. Due to its tumor origins, the early concept of immortality largely represented cancer cells.
 
Immortal Cells vs Cancer Cells

In the late 1950s, Chinese Hamster Ovary (CHO) cell line received the spotlight for their immortalized behavior. It created confusion regarding immortal cells vs cancer cells. The identification of stem cells in the following years only added to the dilemma. Gradually, the Immortal Cell Definition included two different types.
Cancer cells, such as HeLa, HEK293, K562, etc., are found in tumor tissue and have genetic variations that give them immortality.
Stem cells are present naturally in the body, with indefinite lifespan by nature. A few noteworthy examples are MSCs, HSCs, and CHO.

Continuous or immortal lines, thus, found more use in culture owing to their longer lifespan. Additionally, acquiring primary cells was not an easy task, leading to increase in utilization of immortal lines. Their extensive application propelled scientists to develop them by artificially, adding one more type in the immortal cell definition.

Immortalized Primary Cells are developed by inducing immortality in primary cells by different means. For example, COS-7, MDCK, 3T3, etc.

The presence of distinct immortal cell types distinguished them from cancerous cells.

 
Immortalization Process

Scientists analyzed the distinct mechanisms of immortalization:

Telomerase Enzyme: Telomeres are the DNA sequences at the ends of chromosomes. These sequences prevent chromosomal degradation and fusion. However, DNA polymerase cannot fully replicate the 5’-end of the lagging strand during replication. Therefore, with each replication cycle, telomeres shorten, eventually resulting in senescence. Stem cells express the telomerase enzyme that can efficiently extend the telomere region and maintain its length, thereby preventing senescence.
Cell Cycle Dysregulation: The cell cycle has multiple checkpoints distributed across various phases. Each checkpoint ensures cellular integrity and proper completion of the previous phase before moving to the next phase. In case of any aberration, these checkpoints signal the halt of the cycle and initiate either the DNA repair process or apoptosis.
Thus, artificial immortalization employs two techniques:
Viral transfection (SV40, HPV) to disrupt the cellular cycle and promote continuous proliferation. It may also involve the transfection of cell cycle regulators or anti-apoptotic genes.
Transfection of the telomerase enzyme to avoid senescence.
Furthermore, spontaneous epigenetic modifications brought on by specific culture conditions also result in immortalization. RCE1 and 3T3 are two instances.

Advantages
The HeLa cell line fundamentally changed the in vitro culture for a number of reasons:
Long-term culture was possible due to indefinite lifespan. 
Many human or animal tissue primary cells cannot survive longer in a two-dimensional environment, limiting research on them. However, their immortalized version enables deeper investigation.
Immortalization eliminates the need for repeated isolation, reducing cost, time, and labor.
They require less stringent media conditions, simplifying culture protocols.
They are particularly useful for cancer research.
However, the only lacuna of immortal lines is their deviation from tissue properties. Though they provide key information regarding cellular pathways, they do not offer the accuracy of primary cell culture studies.

Conclusion
Immortal cells have significantly contributed to biomedical research. They have improved our understanding of fundamental biological mechanisms in addition to cancer biology, albeit with less precision. They are not the same as cancer cell lines, despite popular belief. The term refers to several cell types.
The widespread application of immortal cell lines particularly originates from their ease of culture or the absence of a primary cell alternative. Therefore, in modern in vitro culture, both immortal and primary cells have their own space. Kosheeka, understanding the value of each, offers both to support your research endeavors.