Stem Cells versus Progenitors
Posted by Teisha Rowland, on 13 February 2011
With so much research focusing on stem cells, I’ve been wondering lately whether researchers are overlooking other important, multipotent cell groups, specifically what are called “progenitor” cells. But then another part of me wonders whether these two groups are so very different from each other. Technically, the main difference between stem cells and progenitors is their lifespan, with progenitors’ being much shorter, but the line here seems blurry; most adult stem cells cannot be cultured for extensive amounts of time before they differentiate or senesce.
I was reminded of the issue of stem cells versus progenitors by a paper that came out earlier this month in The Journal of Clinical Investigation that showed, surprisingly, that patients with androgenic alopecia (AGA), or male pattern baldness, had a normal number of hair stem cells in their scalps, but a depleted number of different hair progenitor cells. The progenitors now look like a likely culprit for AGA. It’s been well-studied how stem cells in hair follicles give rise to new hairs over time, and it’s known that progenitors derived from these stem cells play key roles in this process, but it had not been studied with relation to AGA previously. It’s possible that the stem cells in bald AGA scalps are somehow dysfunctional or inactivated, and this could cause the loss of progenitor cells, but it still needs to be looked into (If you’d like to read more detailed coverage of this paper, I wrote a technical blog post about it on my blog All Things Stem Cell and a layman article on it for my column Biology Bytes.)
I wonder what would have happened to this recent study if when the researchers had found out that the number of hair stem cells was the same in haired and bald scalps, they then moved on to investigating other, maybe non-cellular suspects, without looking at the progenitors. Perhaps they would have then discovered a molecular abnormality in the stem cells, and then suspected the downstream progenitor groups. I just can’t help but wonder how many other diseases and biological phenomena have been investigated with a primary focus on the stem cells involved, when in some cases the progenitors may be a better initial indicator for what’s changed in the system. Or maybe using the terms “stem cells” and “progenitors” is really splitting hairs; stem cells vary significantly in potency and proliferation capacity from group to group, so maybe we should just expand the already expansive term “stem cells” to encompass a broader range of cells. While I like to think that a cell type’s name doesn’t affect whether a researcher studies it, I’d imagine it’s easier to get funding for “stem cell” research than “progenitor cell” research (or, with some funding agencies it may be the other way around), and this may definitely affect a researcher’s focus with funding as tight as it is.
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I hate to see useful distinctions being eroded. I know that the funding has led to “every cell that divides being called a stem cell”, as Austin Smith once put it, but there really is a useful distinction to be made here.
Of course no definition is accepted by everyone, but a reasonable majority consider stem cells to be cells that survive for the life of the organism which both reproduce themselves and generate differentiated progeny. Progenitor cells are those which turn into something else after a period of time short compared to the lifespan.
This means that all cells of the early embryo are progenitors and not stem cells. Embryonic stem cells behave like stem cells in culture but their putative counterparts in the embryo are not stem cells because they soon turn into something else.
In the haematopoietic system, where the development of stem cells has been carefully studied, they are known to arise about E10.5 in the mouse, based on the ability to reconstitute the bone marrow of a lethally irradiated host. So we have the apparent paradox that early embryo cells are not stem cells, but some of their offspring are. This is not really a paradox and it does illustrate nicely that we have two distinct entities here that deserve different names.
Actually you can get funding for “progenitor cells” too. I am a member of a Consortium of the NHLBI devoted to “Heart, Blood and Lung Progenitor Cells”.
In hematopoietic system (the most well studies adult stem cell system) there is a clear distinction between stem and progenitor cells. It based not only on lifespan, which is important characteristic, but mostly on ability to self-renew. In mouse we can passage hematopoietic stem cell serially many generations (from mouse to mouse) during few years. Progenitors aren’t self-renew and characterized by very short lifespan.
I think, it’s important to separate assay-based definitions of progenitors and stem cells, especially for biologists. Defining the difference is important also for physicians and cell product developers. Otherwise the public and business executives will call “stem cell” as any cell. This trend you can see now.
Unfortunately “stem cell” is becoming a label, that you can use to get fund or capital for cell product development. If academic funding organizations still ok about both – progenitors or stem cell (I agree with Jonathan), investors and Wall Street want to hear only “stem cell”. That’s why any “cell therapy” currently accepted as an equivalent of “stem cell therapy”. Many people call hepatocyte or chondrocyte transplantation as “stem cell therapy”. Whatever works for money! Whatever sells. The label “stem cell” is current bestseller.
I’d agree with Jonathan that there is a debate about definition of embryonic stem cell and progeny. What Jonathan was talking about was amazingly described here –
http://www.nature.com/stemcells/2009/0906/090625/full/stemcells.2009.90.html
I think, the right terminology and definition is not just matter of semantics, it’s matter of basic science.
I understand Jonathan’s point but I would side with Teisha – these definitions could really be “splitting hairs” or becoming increasingly redundant. For example, what definitions do we use when stem cell behaviour (lasting throughout life and generating progeny) is the result of the probabilistic behviour of a population of cells? In these cases it appears impossible to distinguish a priori which cells will be the stem cells and which the progenitors. Do we call them all stem cells? Indeed there may not be a distinction between these two types of cells, beyond the vagaries of probability, and one would argue that “stemness” and “progenitorness” are properties of the population and not individual cells.
(See work by Ben Simons and others for more on this type of stem cell behaviour. Nice review in Cell Stem Cell. 2007 Oct 11;1(4):371-81.)
I am still confused .May be the life span criteria short for
progenitor cells and a longer life span for stem cells is a good
one???