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How stem cells make a niche for themselves

Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment.
(Sean Bendall, et al. 2007)

A stem cell is a unique cell type in our body and really magically organized. It’s known that to maintain their fundamental and unique qualities such as self-renewal and ability to differentiate into multiple lineages, they need an appropriate microenvironment called a niche.

For embryonic stem cells (ESC) such a niche is a so-called “feeder cell layer” – usually embryonic fibroblasts that we use to maintain their undifferentiated state in culture. Same story with hematopoietic stem cell (HSC) – the most well known kind of adult stem cell. To maintain their properties in bone marrow they use signals from surrounded cells, such as osteoblasts, stromal mesenchymal progenitors, adipocytes, vascular endothelial cells and maybe some others, which organized into a specific niche for the HSC. If we can figure out these signals we can culture them, multiply and maintain undifferentiated in feeder-free conditions, which could be more scalable for clinical applications.

Two years ago Mickie Bhatia’s group showed for the first time that human ESC can make niche for themselves [1] through autologous derived fibroblasts and IGF-FGF signaling. Now,recent report – Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche [2], published in Nature Cell Biology, showed for the first time that adult stem cell (HSC) can modify surrounded cells in order to serve them like a niche. Well, HSCs are not as potent as ESC, but they can make osteoblasts produce niche signal factors which keep their “stemness”.

Authors used in vitro live-cell imaging co-culture system to unveil communications between human HSC and osteoblasts. The first strong part of the work is imaging. I didn’t see such a beaty before! The picture below demonstrates that HSC-osteoblast contact occurs through specific membrane domain.

This membrane domain can further transform to nanotube (or uropod) – like a bridge between 2 cells:

(pictures adapted by permission from Macmillan Publishers Ltd: Nature Cell Biology 2009;11:303 doi:10.1038/ncb1838, copyright 2009)

The authors demonstrate that at the contact site, containing some signal molecules (CD63, CD133…), portions of this domain was taken up by osteoblasts and internalized into endosomes. Finally, this interaction caused signalling activation inside of osteoblast and increase production of SDF-1 – the main molecule that make HSC home and stay in bone marrow.

It was shown that this interaction is specific for HSC and osteoblasts and does not occur in other cell types (they used Hela cell line as a control to osteoblasts). But it seems like authors forgot yet another important control – CD34-negative cells, sorted from the same sample, to prove that this magic is restricted to HSC only. I was thinking what if HSC is so autonomous that it can do this magic with other types of stromal cells from their natural bone marrow environment (which were not used in control) – stromal mesenchymal cells or fibroblasts or even endothelium?

Another successful example of in vitro remodeling events in the bone marrow niches showed that other proteins are essential to maintain HSC self-renewal – Wnt3a and N-cadherin [3]. I’m just wondering if HSCs are able to make niche cells produce these proteins for their maintenance as well?

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