What is a stem cell anyway?

Posted by Benjamin Buller on

As a biologist, and one who works with bone marrow stem cells in daily life, it’s easy to forget that to the general public, a ‘stem cell’ is not much more than an abstraction, a news-worthy meme that comes light on the details. We scientists take it as a given that we know what stem cells are, but when really pressed, they aren’t so easy to define. The term encompasses many different types of cells that all share a few common features. I will attempt to give a rundown here as to what kinds of cells we mean when we talk about stem cells, and what they do for our bodies.

There is argument in the community over what constitutes a stem cell, but most scientists agree that they share at least three common features. First, they have the ability to regenerate damaged or lost tissue. Second, they can produce at least two cell types. Third, they are extremely rare in any given tissue—our supply of them is far from limitless, even though they can reproduce themselves.

The fist criterion is necessary but not sufficient. For example, the skin has a remarkable capacity to heal itself, but the cells produced by the dividing skin cells are all the same type of, well, skin cell. By most definitions, this disqualifies them from being counted as a stem cell per se, even though they have this common feature with more canonical stem cells. It’s a subtle but important (not just semantic) difference that hopefully will come into better focus below. This brings us to point two.

Stem cells can produce at least two different cell types. On the tree of life that comprises your and my body, cells follow a progression from very general to very specific in their function. Shortly after an egg is fertilized, one can hardly tell any cell from any other. Each could give rise to any type of cell in the body. This phenomenon is termed “pluripotency” (one will also hear “totipotent” but I shall ignore it for our simplified purposes). As time goes on the cells start to take on characteristics that could identify them as a stomach cell, a heart cell, a nerve cell, etc. Once a cell becomes a heart cell, for example, there’s no going back. The cell no longer divides, and a heart cell is all that it will ever be. The cell is said to be “terminally differentiated.”

However, there is an intermediate stage between pluripotency and terminal differentiation. At this stage, a cell has started the journey toward becoming a terminally differentiated cell, but hasn’t reached it yet. Here, a cell can typically become a number of closely related cell types—cousins, if you will. For example, once a cell is committed to being part of the brain, the cell can turn into a neuron, or any of the neuron’s support cells (called glia). However, the cell can’t turn around and become a liver cell at this point—the family tree branches outward but never turns back on itself. At this point, the cell is said to be “multipotent.” That is, it can become multiple different related cells, but not any given cell. Most stem cells are terminally differentiated during development, but some stick around throughout adulthood.
The third criterion is less obvious than the first two. It would seem that stem cells should be abundant. If we had numerous stem cells, couldn’t we repair any given tissue and live forever? Unfortunately, the number of support cells that exist to maintain ideal conditions for our stem cells (the so called “niche”) is quite large. We wouldn’t have the resources to support ourselves if we were made of many stem cells. However, nature has figured out a way to solve this problem: the stem cells rarely divide until tissue is damaged at which point they spring into action. 

Our bone marrow, for example, contains a proportion of stem cells (mesenchymal stem cells—MSC) that is far lower than 0.1% of total cells. However, if they are needed to, say, fix some damaged bone, they start to proliferate at rates orders of magnitude higher than their natural rate, making sure that their numbers aren’t depleted too drastically. 
Unfortunately, as we age, our stem cells’ capacity to self-renew becomes weaker and weaker due to many factors including environmental damage, radiation, etc. It is our position at Forever Labs that we can harvest and leverage our capacity to self-renew by storing our stem cells while they’re still young and healthy. That way, we needn’t worry as much about deteriorating MSCs as we age! 

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