Defining a stem cell product – working proposal and recommendations

by Alexey Bersenev on October 12, 2013 · 1 comment

in consensus

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Last 2 months I was discussing a possible definition of “stem cell product“. I polled professionals and had few opinions exchange via email and LinkedIn. Today, I’m going to summarize this discussion and propose a working definition and recommendations.

Why do we need to define it?
93% of polled professionals think that it is important issue to discuss. 7% think that there is no point to do it. Unfortunately, both sides did not elaborate publicly – why they think so. But I’ve got a good negative feedback, challenging the necessity of this definition. When I say “we”, first of all, I mean data miners, analysts and communicators like me. I’m getting a lot of questions like “what is stem cell therapy?” and “how do you judge which trial is stem cell trial in database?” or “how many stem cell products on the market and in development?” and “how to define stem cell product?” There is no consensus or any recommendations on how to judge “stem cell product/ therapy”. So, my aim is:
to bring some clarity and propose a working recommendations for using  terms “stem cell product” and “stem cell therapy.
I see its potential usefulness for community as following:

  • possibility to quantify and compare data between different analysts and research groups (be on the same page);
  • condemn marketing claims and uncontrolled branding of stem cells, unsupported by solid data;
  • condemn inflated public expectations of “stem cell magic”, fueled by hyped marketing claims;
  • encourage “data-driven”, but not “marketing-driven” classification of cellular products.

Challenges:

  • It’s very difficult to come up with one good and clear definition, because we have a great variety of products. One size will not fit all!
  • Confusion by questions “how to define” and lack of background knowledge. Some people found my poll is really confusing, mostly because it was specifically designed for adult (and neonatal) stem cells, but not for embryonic.
  • Criticism of its practicality. Yes, the utility of definition (if we will have it), may be low for some stakeholders. For example, patients don’t care how you name it – whatever works! Regulators care mostly about the safety and let developer to decide what type of product it is. It could be not very important for physicians as well.

Definition:
Stem cell product is a cellular product, derived from stem cells in vitro via differentiation or containing any quantity of stem cells, anticipated major mechanism of therapeutic action of which attributed exclusively to stem cells or their ex vivo derivatives.

Explanation:
I was trying to fit it all. It could be applied to all kinds of stem cell products – embryonic, adult and anything else.
“derived from stem cells in vitro via differentiation” – covers any cellular product, containing differentiated cells or progenitors, derived from ES-, iPS-, neonatal-, adult- stem cells ex vivo.
“containing any quantity of stem cells” – means irrespective of stem cell enrichment, quantity and purity. For example, such products as bone marrow mononuclear cells, adipose-derived stromal vascular fraction and hematopoietic grafts may contain “very few” stem cells, but could be “stem cell products”.
“anticipated mechanism of therapeutic action” (MOA) – covers situations when product was intended as “stem cell”, but did not act as such after administration (hematopoietic graft in leukemia without long-term chimerism).
“major mechanism of therapeutic action” – covers products with multiple MOAs, but defined the “major one”. For example, hematopoietic graft in leukemia – major = life-long multilineage blood chimerism – caused by stem cells, other – rapid short-term neutrophil or platelet recovery – caused by committed progenitors.
“attributed exclusively to stem cells” – covers fresh (bone marrow mononuclear fraction of fat stromal vascular fraction) products with low stem cell purity, but proven attribution of stem cells within the product to major MOA. Covers cultured (mesenchymal stromal cells, neural stem cells) products with highest stem cell purity, because at such high purity MOA will be attributed exclusively to those stem cells.
“attributed exclusively to their ex vivo derivatives” – covers all products, derived from pure stem cells as starting material (ES-, iPS-, neonatal-, adult-), containing differentiated mature or progenitor cells and not containing residual stem cells.

Recommendations:

  1. This definition should be considered by: researchers, consultants, analysts, data miners, product developers and manufacturers for classification of cellular products and designation of therapeutic intervention.
  2. Cellular composition of product should be well characterized.
  3. Attribution of stem cells or their ex vivo derivatives to MOA should be proven and supported by solid pre-clinical or clinical data.
  4. If MOA or its attribution to stem cells can not be clearly determined, using terms “cell (cellular) product” and “cell (cellular) therapy” is recommended.

Considerations:

  • This definition applies to all types of stem cells.
  • This is working proposed definition, which open for discussion and could be change in the future.
  • This definition is challenging wide-spread designation of fresh bone marrow mononuclear cells, adipose-derived stromal vascular fraction and other complex tissues as “stem cell products”.
  • This definition is data-driven.

I’d like to thank everyone, who voted in a poll and discussed this issue with me!

{ 1 comment… read it below or add one }

Greg October 20, 2013 at 1:36 pm

Why so quick to dismiss certain therapies. Saying something does “not work” seems to say that everything has been tried thus diabetes is hopeless with cell therapy. I think that may be premature.

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