Stem cells and mesenchymal cells: Let’s make it clear
There is a sentence I often hear when people talk about regenerative medicine: “It’s wrong to talk about stem cells, you have to say mesenchymal cells.” It’s claimed both by doctors and non-experts, but to understand how strange this phrase sounds, you should read the following example.
To celebrate his job promotion, Andrew asked Juliet out for dinner, promising her to pay for it. As the bill comes, Juliet remembers his promise and asks Andrea: «You have the money, don’t you?». The man, after checking his wallet, replies: «No, I only have cash.»
To tell in an article what a stem cell is would not do justice to a biological prodigy that now is the absolute protagonist of biomedical research. Moreover, I would risk boring the reader, or even worse, confusing him: the exact opposite of this piece’s intent. I will only describe two properties for which these cells are so appreciated: self-renewal and differentiation.
Through self-renewal, a cell can clone itself during replication. When a stem cell divides, at least one of the two daughter cells does not undergo any modification and remains identical to the mother cell. This is important for the stem cell pool to remain quantitatively stable over time. With the onset of pathologies and the progress of aging, this ability weakens.
With differentiation, a stem cell can specialize in a tissue-specific function, such as: being a skin cell (keratinocyte), a muscle cell (myocyte), a nervous system cell (neuron). Differentiation is a progressive process that takes place through epigenetic modifications, i.e., changes that silence parts of the DNA that are not useful for those specific functions. In this way, only the valuable genes remain active and what was once a stem cell can now replace damaged cells and contribute to the functioning of a tissue.
Stem cells can be adult, or “less adult” and differentiation potential can be toti-, pluri-, multi-, oligo- or unipotent. The next paragraph will help us to understand these differences.
The myth of the stem cell is born through the belief that it can regenerate any tissue. A totipotent stem cell can give rise to everything (even to life). A pluripotent stem cell can give rise to almost everything (it cannot generate an organism from scratch). The latter exists only in the embryo, or it can be obtained through the reprogramming of an adult cell by reversing the process of differentiation. There are ethical issues with embryos, and reprogramming exploits advanced cell manipulation techniques, such as the Yamanaka method (Nobel prize for medicine in 2010 for the famous iPSC – induced Pluripotent Stem Cells) or the somatic cell nuclear transfer (do you remember Dolly The Ship?).
However, if we take a step back, there are also adult stem cells that can be multi-, oligo- or unipotent. Multipotent stem cells cannot differentiate in all tissues as pluripotent ones, but only in those falling under the same embryonic origin. As suggested by the mes- prefix, mesenchymal cells are adult stem cells that can differentiate in all tissues originated from mesoderm (the germ layer that originates the musculoskeletal system, blood cells, and other organs). They were first identified in bone marrow in 1970, then in different tissues and only in 2001 in fat. In regenerative medicine, they are appreciated for the simplicity of the harvest and use. Even if they cannot differentiate in all cell subtypes, they have an excellent stem cell capacity that we have not mentioned so far. In response to the environmental stimuli, they can release molecules able to promote regeneration.
Not all stem cells are mesenchymal cells, but all mesenchymal cells are stem cells. In scientific literature, the chosen acronym is always MSCs, which stands for Mesenchymal Stem Cells. The doubt, for researchers, is of a different kind. In 2008, a discovery claimed that MSCs derive from pericytes, which are contractile cells that surround capillaries. It is not yet certain whether all MSCs originate from pericytes, but it is sure that not all pericytes become MSCs.
If the last sentence is somehow confusing, that’s because biology is complicated. However, there is one thing that we can be sure about: if you know your meaning, it is not dangerous to talk about stem cells. Indeed, you may risk giving a good impression.
Pierre Charbord. Bone marrow mesenchymal stem cells: historical overview and concepts. Hum Gene Ther. 2010 Sep; 21(9): 1045–1056. DOI: 10.1089/hum.2010.115
Patricia A. Zuk. The Adipose-derived Stem Cell: Looking Back and Looking Ahead. Mol Biol Cell. 2010 Jun 1; 21(11): 1783–1787. DOI: 10.1091/mbc.E09-07-0589
Arnold I Caplan. All MSCs Are Pericytes? Cell Stem Cell 2008, 3 (3), 229-30 DOI: 10.1016/j.stem.2008.08.008