Stem cell self-sufficiency – making normal and malignant niches

by Alexey Bersenev on February 10, 2011 · 0 comments

in cancer stem cell, niche

I’ve written before about how stem cells can make their own niches. I’d like to expand this topic and summarize some recent findings. I’m going to talk about stem cell self-sufficiency as an ability of stem cells to make or modify the niche for themselves.

In vitro studies
The first studies in vitro described this phenomenon for embryonic stem cells and hematopoietic stem cells (HSC). It was shown that HSC can modify surrounding cells (osteoblasts) through direct contact by membrane domain (uropod) in order to make them serve as a niche.

Darwin Prockop’s group described a phenomenon of so-called transient “quasi-niches” made by mesenchymal stem cells (MSC) in culture:

Unusual features of MSCs in culture were also apparent from observing the cells after they were plated at clonal densities. The cells expanded as single-cell derived colonies but the properties of the cells changed as the colonies expanded. In the many of the colonies that formed, distinct inner and outer regions were apparent. The outer regions consisted of rapidly self-renewing cells (RS-MSCs) and the inner regions consisted of slowly replicating cells (SR-MSCs) that were partially differentiated.
Therefore, the MSCs expanded at clonal densities appeared to reversibly create their own microenvironments or “quasi-niches” in culture in a manner that paralleled their ability to provide niches for hematopoietic stem cells.

Ghosh was able to isolate a single tracheal stem cell that generated its own niche in vitro. Recent findings from Hans Clevers group’s suggest that stem cells in the small intestine can generate their own niche.

In vivo studies
Recently Elaine Fuchs group used lineage tracing and cell cycle analysis in vivo in order to demonstrate relationships between hair follicle stem cells and their niches:

…our data show that a downstream lineage of SCs can be a critical component of the niche microenvironment and regulate the rate of SC divisions.

The last data on adult stem cells and their niches highlights the possibility of linear relationship between them.

Cancer stem cell self-made niches

Now there are a few reports, suggesting that cancer stem cells can make niche cells for themselves. Majority of work in this area was done on brain tumors. Earlier study from last year demonstrated that glioblastoma stem cells could be responsible for creating a vascular niche for themselves.

Two very recent reports [1; 2], added more intriguing data in the relationships between cancer stem cells and their malignant vascular niche:

Excerpt from the commentary:

Two studies now add a new twist to the angiogenesis field. Groups led by Tabar and De Maria independently observed that a high proportion (up to 90%) of endothelial cells in human GBM tumors carried the same abnormal genomes as the malignant GBM cells, suggesting that endothelial cells are derived from the tumor cells rather than from normal surrounding vessels. In fact, both groups demonstrated this directly by digesting GBM samples into single cells and either growing them in culture or injecting them into mice. In both cases, human endothelial cells were formed. Intriguingly, it was the cancer stem cell fraction—characterized by CD133 expression—that had the ability to form endothelial cells.

In conclusion, many stem cells have demonstrated remarkable self-sufficiency in terms of generating their own niche or modifying surrounding cells in order to serve them. How we can use this new knowledge therapeutically is the subject of further investigations.

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