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The value of stem cells in commercial cell therapeutic products

We are all so excited about the possibility of using stem cells for therapy. There is no doubt, stem cells have a huge therapeutic potential. But potential could be very different from reality. I was trying to find any commercial stem cell product available on the market, but didn’t succeed in my search. Well, maybe it’s not a prime time yet? I hope so, but I think even in the near future the value of stem cells in commercial cell products will be low.

So, what is considered a “stem cell product”? If stem cells underlie the mechanism of therapeutic action of the product, we can call it “stem cell product”. Even if it’s not pure and contains only as low as 1% of stem cells. If ex vivo or in vivo progeny (progenitor or mature cell types derived from stem cells) underlies the mechanism of therapeutic action of the product, we can call it “stem cell-based product”. This type of product can contain some stem cells, but they do not underlie the mechanism of therapeutic action. Other types of cell products could contain only progenitors or mature cells without stem cells and their derivatives.

According to Michael Lysaght [1], in 2008 there were more than 50 stem cell products in preclinical/clinical development in 66 companies. Since that none of them made to the market yet. Currently we have about 60-70 commercially available therapeutic cell products on the market [2]. All of them based on progenitor or mature specialized cell types. Commercial cellular products, based on differentiated cells, have been on market for a while – since 90s of the last century (Apligraf, Carticel, ect.). Now, all of us are eager to see how stem cells will fit and merge with Regenerative Medicine industry (Regen).

I think it will be very hard for developers to promote the stem cell product to the market. The main hurdle could be product characterization. For example, a potency assay is required for product lot release and answers the question of therapeutic mechanism. The problem is that many developers don’t know why their stem cell product actually works. Let’s say total cord blood mononuclear cells, contain some types of stem cells and are proposed for use in therapy of many “nonhematopoietic diseases”. What type of cells underlies therapeutic effect in this mixture? What potency assays should be developed to justify product release criteria under FDA regulation? Maybe non-stem cells underlie mechanism of action of the product which is composed of the mixture of mononuclear cells. What if we look at potency of the product after stem cell depletion? Maybe we don’t need them at all?

Other problem is heterogeneity of stem cell populations. Even withing hematopoietic or mesenchymal stromal stem cells (MSC) there are some subsets with different qualities. How to characterize them in order to product standardization?

I think so-called “stem cell-based products” have more chances for successful commercialization compared to pure “stem cell products”. Even if they still contain some stem cells, they are mostly composed of derivatives – progenitors and differentiated cells that arose from stem cells. As an example of such product I’d like to point out to “Osteocel [3]” – for bone tissue regeneration. This product commercialized by Nuvasive [4] is available on the market. Osteocel is allogeneic osteogenic derivatives from mesenchymal stem cells.

In terms of future perspectives, I remain skeptical about the possibility for many stem cell products getting into the market. I think in the next 5 years, we will get a few (I expect at least one – Prochymal [5] from Osiris), but overall value of stem cell products in total number cell product will remain low. In my opinion, the most important reasons will be the following:

  1. In products containing a mixture of mononuclear cells we don’t know what cell population underlies the mechanism of therapeutic action. Therefore characterization and development of potency assay for such product is a very difficult task.
  2. Even pure expanded ex vivo stem cell products (for example, MSC) are still heterogenous and hard to characterize.
  3. In many conditions we frequently don’t know what is therapeutic mechanism of infused stem cells. So, how will we develop potency assay for the product? For example, in case of MSC, we just realize that there is NO such mechanism as transdifferentiation into the other tissues, but there are a variety of other, so-called trophic mechanisms (angiogenesis, immunomodulation, anti-apoptotic, anti-proliferative…). So, which one should we pick for potency assay?
  4. Opposite to the stem cell, products based on mature specialized cells are easy to characterize. A lot of them are applied for so-called “homologous use”, which make commercialization and approval process much easier. For example – chondrocytes for cartilage repair, skin cells for burn treatment.
  5. Many R&D guys in companies will realize (and maybe even tell us) sooner or later that the stem cell that they are trying to commercialize actually doesn’t fit the scientific definition of “stem cell”. Simply because we still can not figure out how to maintain stem cells in undifferentiated condition outside of the body.
  6. The presence of stem cells in the cell product may required (by regulatory agencies) additional tests for safety – tumorigenecity.

Well, if stem cell products development is associated with so many difficulties, maybe we don’t need them at all? Maybe Regen and cell therapy will do fine without stem cell products? What do you think?