30 - Cells as Model Systems (w/ Grace Usher!)
30. Cells as Model Systems
Repel! I’m a cell. The word may be a bit nebulous, but cells are the smallest unit of life that we can define, and all living things are made up of cells. Today, we’ll discuss using human cells as models for research and how those “cells-in-dishes” are different than the cells in our very own bodies. Let’s learn to be scientifically conversational.
General Learning Concepts
1) What is a cell? What is some background on cells?
a. What is a cell? “Cells are the structural and functional unit of all living organisms.” Some organisms are singe-cellular (episode 14, what are bacteria) while others are multicellular (humans, estimated to have 37.2 trillion cells that human or origin). As discussed in episode 22, Eukaryotic cells have a variety of compartments that have various functions. 
b. What is the difference between a cell in your body and one in a dish? Cells in a dish can respond to one another, but they’re all the same cell type. For example, a famous cell line is from cervical cancer, so all of the cells are the same. Primary cells, or cells taken from living tissue, can only undergo a certain amount of divisions. Additionally, some cells used in a dish are “immortalized”: they have different amounts of DNA that somehow result in the ability to divide many more times in a row than a primary cell in a dish would. Cells in a dish are often arranged as a single layer that is homogeneous; organs in our body are often arranged in very specific ways to support life. 
c. What is a model? It’s hard to learn every single thing about every single organism. Using systems that seem to be generalizable allows for comparisons and development of more complex, in-depth experimental developments.
i. Very similar to a model in real life; you can’t necessarily picture what you’ll look like with that jacket until you see it on the model. That being said, it’s not the picture of what you look like, but it is representative. Some models are better than others.
ii. Is the organism good to rear? Is the size convenient? Is it inexpensive? How long is the lifecycle? Can you manipulate the genetics? Will the results be useful? Will others use the model?
iii. Example: The natural course of a disease in humans may take dozens of years. In contrast, a model organism can quickly develop a disease or some of its symptoms. That allows researchers to learn about the disease in a much shorter time
2) What are the pros and cons of using cells as models?
a. Pros: Often thought of as pure populations, which gives consistent and reproducible results. Cell lines tend to be quite cheap, often provide a seemingly unlimited supply of materials, and avoid common ethical issues (partially) of using humans or animals as test subjects. These cells can be shipped across the world to provide the same system to use for studies with collaborators. The cells do not require hefty maintenance when compared with animal models, and replicate quickly to allow for faster data collection. There are generally not many additional training requirements required to be able to work cells in a dish, and the cells are capable of genetic manipulation (for example, cutting out a gene or putting one in). 
b. Cons: Over time, genetic evolution adapts to an environment (like a petri dish), which does not represent the true organism. It can also be challenging to know exactly what a cell is and where it came from. Other cells can be “aggressive” and contaminate a pure culture, which can lead to termination of the entire culture (eg. HeLa cells or mycoplasma). Tumorous cell lines may not properly represent the primary cell line they are derived from and those cells may not interact as they normally will with their neighbors. 
3) What is the historical basis of using cells as model systems?
a. First occurrence: 1951, Henrietta Lacks was found to have a malignant tumor in her cervix. A sample of that tumor was removed by a surgeon and was passed on to Dr. George Gey, and he found that unlike the other cells he had collected over the years, these cells continued to double every (roughly) 24 hours. Henrietta Lacks died later that year but her cells are still being used today. There are severe and important ethical issues that come up with this very topic, from information and consent to how these cells were used by Jonas Salk to help develop the polio vaccine.  
i. It is impossible to separate cell culture from the legacy of Henrietta Lacks, but her story deserves more time than this episode can dedicate. There will be an entirely separate episode for Henrietta Lacks. A famous book, “The immortal life of Henrietta Lacks”, by Rebecca Skloot, details further.
b. Primary Cell Lines: Primary cells are directly isolated from human or animal tissues. Sensitive cells that require additional nutrients that are not found in the liquids required to support life in a cell line that has been immortalized. These liquids required are specific to the identity of the cell. These cell lines tend to be diverse in composition, and allow for taking into account factors like age, medical history, race, or sex. 
c. Organoids: A newer technology that are essentially self-organized 3D tissue cultures that derive from stem cells. They can be small and thin as a hair or millimeters in diameter. Stem cells have the instructions (with the right nutrients) to end up in these complex structures and make populations of cells that properly represent organs (like the brain, kidney, lung, intestine, stomach, liver). These organoids contain thousands of cells and are useful for studying complex, human-like characteristics of disease.
4) Fun Tidbits
a. Stem cells: Stem cells are special human cells that can develop into lots of different cell types, and sometimes can help repair tissues. There are not only stem cells in embryonic tissues: they are also found in adults, but they are usually a little more developed. For example, those cells are more likely to generate very certain types of cells (a stem cell derived from the liver will only make more liver cells).
5) Solicited Questions
a. Do cells have immune systems? Some do, and some do not. It depends on the cell type whether or not there can be primary immune responses, as to generate antibodies is a very complex reaction that uses more than one cell type. Still, even in fully grown humans, we have immune privileged sites (the eye, for example) to prevent loss of function.
b. How long does it take for a cell to split? This depends on how much nutrient is in a culture or tissue, if there are any toxic molecules building up, and many other environmental factors. For human cells, this number ranges from hours to days.