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Comment 06

Please cite this contribution as follows: Alexey [Bersenev]. Ilya, My summary based on experimental data, published intensively in. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_06. doi:10.3205/maximowaward_2012_blog-comment_06

This contribution is provided under the following license: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Alexey. May 30, 2012 at 4:06 pm

Ilya,

My summary based on experimental data, published intensively in the last 7 years. These data indicate to high degree of heterogeneity in adult bone marrow HSC population. I’ll give you few examples and references.

If you take a single HSC and transplant it, you can see different patterns of repopulaion in primary recipients: myeloid-, lymphoid- biased and balanced. The ultimate test for “stemness” is serial transpant. So, if we look at secondary transplant, we can see that balanced HSC can give balanced or myeloid- biased repopulation, myeloid-biased HSC can give balanced or myeloid-biased repopulation and lymphoid biased HSC can give balanced or lymphoid-biased repopulation in secondary recipients. So, balanced HSC can become myeloid-biased, but the most typical case is the opposite – when in primary recipient we can see only myeloid repopulation, but in secondary – robust multilineage. All of these HSC subsets passed self-renewal test and therefore we can call them “stem cells”, based on current international consensus. If myeloid-biased HSC is not really “stem” but “commited progenitor” (as you’re saying), they will not self-renew or will give only myeloid repopulation in secondary recipient. It’s not the case in single cell transplantation assays. You have to understand that we can clearly separate HSC from their progenies by transplantation assays, but not by markers. Please read: Dykstra 2007, Morita 2010, Benz 2012. This is a current consensus between many groups, studying HSC around the world – Connie Eaves, Nakauchi, Goodell and others. They performed as many as few thousand of single cell transplants and published about 10 papers on this subject. One can argue that “biased HSC” are commited progenitors, but experimental data indicate to opposite – they retain multilineage repopulation capacity throughout lifespan.

I’m not sure to what authors and time you’re referring when talking about “classic histology”. Stem cell field is so dynamic right now, that some chapters of textbooks should be revised every 5-10 years or so. For example, still 3 years ago we had a dogma in the field that all HSC are quiescent and not cycling. But now we have got some evidence, that HSC can go to cycle and quiescence back and forth, depending on necessity and feedback signals. One quiescent HSC could undergo 5 divisions and then become quiescent again, retaining the ability to self-renew and reconstitute many blood lineages.

So, all HSC subsets reside in dynamic equilibrium. HSC heterogeneity makes a lot of biological sense.

This contribution is provided under the following license: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Please cite this contribution as follows: Alexey [Bersenev]. Ilya, My summary based on experimental data, published intensively in. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_06. doi:10.3205/maximowaward_2012_blog-comment_06

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