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Comment 04

Please cite this contribution as follows: Alexey [Bersenev]. The current definition of “stem cell” include 2 essential characteristics: Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_04. doi:10.3205/maximowaward_2012_blog-comment_04

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 4:17 am

The current definition of “stem cell” include 2 essential characteristics: the cell which (1) capable to self-renew (or reproduce itself) and (2) capable to give many (pluri- or multi- potency) mature cell types (lineages). Although this definition causes some discussion, especially among embryonic stem researchers, that’s the best we have today. Yet another hallmarks of adult stem cells include: niche, specific cell cycle and regenerative potential (ability to heal or rescue missing cell types).

Hematopoietic stem cell (HSC) fits perfectly in this definition. We can assess self-renewal capability of HSC and easily measure their multipotentiality. Bone marrow transplantation and enriched purified HSC transplantation allow us to assess multipotentiality in vivo and quantify the number of functional HSC. Serial transplantation (from mouse to mouse) allow us to track single HSC and therefore provide an evidence for self-renewal. This is functional definition. There is a weak correlation with particular HSC markers due to high heterogeneity of their population. For example, surface markers allow to enrich some HSC subpopulations, but not guaranteed functional performance. Thus, only one out four highly purified (based on 6-8 markers) human HSC will self-renew and possess multipotentiality in xenotransplantation model. Because we can not assess self-renewal in human, we can define HSC after transplantation by life-long multilineage engraftment in bone marrow and chimerism in the blood.

The problem of HSC heterogeneity was studied in details in the last few years. The current concept implies co-existance of few sub-populations (or clones) HSC with different patterns of lineages repopulation (-potentiality): myeloid-, lymphoid- biased and balanced. Existence of these clones doesn’t cancel HSC definition, because all of them able to self-renew, means engraft and repopulate in serial transplantation assay. These HSC subtypes could also have different cell cycle status and kinetics. So, adult HSC is a dynamic population, which consist of different clones with different blood repopulation patterns and equilibrium of quiescent and cycling states. Now we’re getting close to realization that adult HSC can’t not give absolutely all (100%) of different blood cell types. Some of adult HSC can never give tissue macrophages or some B-cell subsets. According a current hypothesis, these blood types have developed as embryonic remnants from embryonic HSC.

So, in the definition debate, HSC could serve as good example of how “stem cell” can be defined and measured in assays.

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]. The current definition of “stem cell” include 2 essential characteristics: Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_04. doi:10.3205/maximowaward_2012_blog-comment_04

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