Does plerixafor destroy the hematopoietic progenitor cell/mesenchymal stromal cell niche?

Abstract

Tissue homeostasis is dependent on replacement of damaged and aged cells, and stem cells are the primary source of new cell generation. Most tissue and organs of the body contain stromal cells that are part of the stem cell niche and are essential for the maintenance, proliferation and differentiation of stem cells. Hematopoiesis is a well-characterized tissue system in which interactions between hematopoietic stem cells (HSCs) and stromal cells in the bone marrow (BM) have been clearly established (1e3). The BM environment is subject to complex regulation that is critical for hematopoiesis. Many studies have demonstrated the production of both stimulating and inhibitory factors by BM stromal cells (mesenchymal stromal cells, MSCs) (4e6). However, the full potential of MSCs and their role in control of the HSC proliferation and differentiation remains unclear. Critical to sustained hematopoiesis is themaintenance of stem cell quiescence. Without a niche in which a stem cell pool can reside unstimulated by proliferative and differentiation signals, hematopoiesis cannot be sustained life-long. There is evidence that HSC quiescence is at least in part regulated by direct contact between HSCs and MSCs. This contact is mediated through chemokine receptor 4 (CXCR4) on HSCs engaging stromal cellederived factor (SDF)-1 on MSCs (7). With the advent of plerixafor—a CXCR4 antagonist used to mobilize HSCs for stem cell transplantation—it is pertinent to ask how this agent interferes with HSC/MSC interactions. In this issue of Cytotherapy, Ludwig et al. (8) cocultured HSCs and MSCs with and without plerixafor, studying cell division kinetics and stem cell surface marker changes to explore the relationship between HSCs and MSCs and the role of the CXCR4/SDF-1 axis. They found that co-culture of