Journal Club: What is a Stem Cell?

This is a new writing exercise in which I'll post about an article that was discussed in my lab's journal club. Recently, we read a new paper by some preeminent figures in the stem cell field.

The paper, No Identical ‘‘Mesenchymal Stem Cells’’ at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels, was published in June 2016, in the journal Stem Cell Reports. The full text of this open access paper is available here.

A new paper by Benedetto Sacchetti, part of recently deceased Paulo Bianco's research group, seeks to clarify some much needed points in the world of mesenchymal stem cells or MSCs, and their lack of universally accepted definitions. In fact, the authors also argue against using the term “MSC,” as it is misleading. They claim that stem cells should be named by their tissue of origin instead, because as shown, these cells retain characteristics of where they were isolated from, despite sharing some similarities.

An increasing number of stem cell clinics are popping up, claiming everything from anti-aging benefits to curing diseases. These clinics are pulling *something* out of people, calling this random slurry "stem cells," and injecting it back into clients. This is a false and dangerous practice. While stem cells have great therapeutic potential, there is still much work to be done in basic research before these claims can be verified or even tested. This issue is further complicated by some people in the stem cell field that claim “MSCs” can cure everything from stroke to osteoarthritis. While some of the research is promising, there is no clear definition of an “MSC," let alone well documented therapies.

In Sacchetti's paper, they clearly show that stem cells from different tissues have different abilities to differentiate, and are not ubiquitous, despite having some similar characteristics. The authors look at cells from four different tissues: bone marrow, muscle, the outer surface of bone, and umbilical cord blood. 

Currently, stem cells are isolated for research using proteins that sit on the surface of the cell. This paper shows that despite having similar surface markers, cells from different tissues have clearly distinct gene expression patterns, shown with two different clustering techniques. Each of the four types of stem cell retain a gene expression pattern that is directly related to their respective tissue of origin. 

Next, this paper explores the differentiation ability of stem cells from different origins. Only the cells from bone marrow or periosteum (also a bone-related tissue), were able to form new bone, complete with bone marrow inside. Cells from muscle did not make bone, and cells from cord blood weren't able to form complete bone marrow. The ability of a cell to make new bone, including bone marrow is a defining marker of a skeletal stem cell. 

Following this, they looked at the ability of these four types of stem cells to differentiate into muscle. As before, only the cells that were isolated from muscle retained the ability to differentiate into muscle, while the other three were not. This was also shown by looking at the ability of these cells to regenerate muscle after an injury, and again only the muscle derived cells were able to make new muscle. 

The overarching point of this paper is that cells from different tissues shouldn’t be uniformly referred to as “MSCs”, when they clearly show differences. Instead, they should be referred to by their tissue of origin. While there are some similarities, the inherent ability of each cell type to differentiate is different.