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Comment 07

Please cite this contribution as follows: Ilya [Bozo]. Alexey, do you think, before I formed my point of. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_07. doi:10.3205/maximowaward_2012_blog-comment_07

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

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Ilya. May 30, 2012 at 8:06 pm

Alexey, do you think, before I formed my point of view, I have not read the experimental and clinical data of the last ten years? I certainly know the researchs of respected scientists, who were listed in your comments. However, interpretation of the results of these studies is not so clear. I would have explained more precisely in Russian, but I’ll try in English :) .

You said that ‘the ultimate test for “stemness” is serial transpant”. However, it is not. The ultimate test for “stemness” is clonal analysis, in which the researcher obtains from a single cell whole colony of cells, it is absolutely identical to the primary cell (this is a classic proof of self-renewal). While the method of serial transplantations is characterized by manipulating with groups of cells. It is indicated in the articles which you have listed.

Now define the meaning of the term “heterogeneity”. First of all, this concept represents a different origin. However, in the scientific literature, the term “heterogeneity” has a wider meaning and is used when we select any subpopulations of cells (in this case, the cells may have the same origin, but significantly (and consistently) different from each other by phenotypic and functional features). Do you agree?

Now back to your examples. You have written:
“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.”

I consider that enumeration of these results deny your own opinion. I will try to illustrate the idea by the following examples. We have two criteria, namely a capacity of differentiation and self-renewal (two variables). So, if in serial transplants lymphoid-biased HSC (for example) give lymphoid-biased repopulations always and have a self-renewal, they would have to be considered as a specific “subpopulation” of HSC. Another option: lymphoid-biased HSC give a lymphoid-biased repopulations always in serial transplantation, but have not a self-renewal. In this case, these cells should be called “the closest derivatives” of HSC (it is not a “stem cells” already). The third option corresponds to your examples: lymphoid-biased HSC can give lymphoid repopulation in primary recipients, but it can give balanced or lymphoid-biased repopulation in secondary recipients and have a self-renewal. What does it mean? In my opinion, this means only one thing … This subpopulation (lymphoid-biased), as well as myeloid-biased and balanced are not “subpopulations”, it is a single population of HSCs. The changes of differentiation potential, which formed the basis for separation of subpopulations, are transient and highly conditional. The specificity of microenvironment causes transient changes in differentiation capacity of HSCs population. The factors of microenvironment may be different in composition and intensity in different areas of bone marrow stroma even within a single bone (eg, ilium). It is therefore logical that the cells within a population of HSCs differ from each other. But these changes are not stable, it is caused by factors of microenvironment, which act at the specific period of time. In the end, there are not two identical cells within a single population. However, it does not mean that it is necessary to separate populations in a number of 1000 cells (for example) to 1000 subpopulations. In this interpretation, it becomes apparent why we observe a prevailing any differentiation (lymphoid or myeloid) in case of primary recipient, and another differentiation in the secondary recipient (it is another organism with the other factors of microenvironment).

P.S. Of course, textbooks should be revised every 5-10 years (even more often) but the classic works of Maximow, Zavarzin, Khlopin, etc. are called “classical” not without purpose… It is relevant to this day.

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

Please cite this contribution as follows: Ilya [Bozo]. Alexey, do you think, before I formed my point of. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_07. doi:10.3205/maximowaward_2012_blog-comment_07

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