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Comment 10

Please cite this contribution as follows: Kshama Gupta. Dear Colleagues, I believe that this is a topic on. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_10. doi:10.3205/maximowaward_2012_blog-comment_10

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

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Kshama Gupta. May 31, 2012 at 11:19 am

Dear Colleagues,

I believe that this is a topic on the usage of the term HSC, being biased medically, scientifically and of-course, hence forth regionally, is a topic of immense debate and discussion.

Foremost, we all would agree and appreciate that a hematopoietic STEM cell conceptually, is the one having ability to contribute to all the cell lineages of blood.

The intensive search for the population of such cells having the ability to self renew and repopulate began right after the disaster of Hiroshima and Nagasaki in 1945. In 1956, three laboratories demonstrated that the injected bone marrow cells directly regenerated the blood-forming system, rather than releasing factors that caused the recipients’ cells to repair irradiation damage. To date, the transplantation of these Hematopoietic stem cells, is the only known treatment for Bone Marrow Failure syndromes and to regenerate the blood forming system.

However, this population of cells we term the “HSC” medically does not comprise the pure population with the homogenous property of “Stemness” (i.e. Self – Renew and re-populate the various Hematopoietic lineages), and is rather a mixed population of Hematopoietic stem / progenitor cells at different stages of differentiation.

A major thrust of basic HSC research since the 1960s has been in identifying and characterizing the true stem cells. The challenge is formidable as only about 1 in every 10,000 to 15,000 bone marrow cells is thought to be a stem cell. In the blood stream the proportion falls to 1 in 100,000 blood cells.

Further more its known that the short-term blood-progenitor cells in a mouse may restore hematopoiesis for three to four months (Harrison et al) and the longevity of short-term stem cells for humans is not firmly established. A true stem cell, capable of self-renewal, must be able to renew itself for the entire lifespan of an organism. It is these long-term replicating HSCs that are most important for developing HSC-based cell therapies. Unfortunately, to date, researchers cannot precisely distinguish the long-term from the short-term cells when they are removed from the bloodstream or bone marrow.

In 1988, in an effort to develop a reliable means of identifying these cells, Irving Weissman and his collaborators focused attention on a set of protein markers on the surface of mouse blood cells that were associated with increased likelihood that the cell was a long-term HSC. Four years later, the laboratory proposed a comparable set of markers for the human stem cell. However, the groups of cells thus sorted by surface markers are yet heterogeneous and include some cells that are true, long-term self-renewing stem cells, some shorter-term progenitors, and some non-stem cells. Although it has been shown that a purified population with surface markers as CD34+, Thy1+ and Lin- swiftly engraft, yet a great deal of re-consideration is required when we talk about Stem Cells in Hematopoietic system. Moreover, to isolate mesenchymal stem cell with respect to the hematopoietic cell population from bone marrow has been another challenge due to certain overlapping markers.

In agreement with the post by Ilya, I would also say that the use of the terminology by Muller-Sieburg et al. (2012), which divides the HSC into three subpopulations by their differentiation capacity: myeloid-biased, balanced, and lymphoid-biased HSCs, however does not follow the classical definition of Stem cells for two of the sub-populations included; Being already committed to follow one of the lineages down stream, these would no longer give rise to all the Hematopoietic cell types. There are several research groups working on the differentiation models (ie. Stochastic, Determinant, Selective or Instructive – Lineage specific, or Combination Models) so as to address the issue of heterogenecity in the population of HSC and their differentiation paths taken under the influence of the niche / microenvironments / stimuli; A mixed population of CD34+ cells in presence of a particular cytokine / Growth factor would all majorly behave in a similar manner, while in presence of a combination of different stimuli would chose to diverge and differentiate to multi-lineages. Hence to classify the pre-committed cell types as progenitors with a mixed population as stem – progenitors, giving appreciable consideration to the sub-populations derived from the actual HSC, would be more appropriate. We hope with the ongoing advancements in identifying and isolating the pure population of LT-HSC or its immediate descendants at a single cell level would open new avenues for a further precise distinction and classification of the Hematopoietic stem / progenitor repertoire.

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

Please cite this contribution as follows: Kshama Gupta. Dear Colleagues, I believe that this is a topic on. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_10. doi:10.3205/maximowaward_2012_blog-comment_10

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