Evaluating Stem Cell Microenvironment Interactions Transplantation and Mobilization

When Till and McCulloch demonstrated that transplanting mouse bone marrow cells into lethally irradiated recipient mice could rescue them from death and lead to the formation self-renewing hematopoietic colonies on the spleen, they demonstrated the cell-based nature of transplant-mediated rescue and forever incorporated the concept of migratory capacity into our definition of a functional HSC (McCulloch and Till 1960, Till and McCulloch 1961, Becker et al. 1963, Siminovitch et al. 1963). Since that time in the 1960s, the vast majority of experiments designed to investigate HSC function have used some form of transplantation assay to prove the nature and identity of the cells under investigation. In light of the important role that transplantation and mobilization studies have played in the development of our understanding of HSC function, we will briefly review the current understanding of these processes. For more extensive information, see the following reviews: (Lapidot and Petit 2002, Askenasy et al. 2003, Papayannopoulou 2003, Papayannopoulou 2004, Lapidot et al. 2005, Cancelas et al. 2006, Chute 2006, Yaniv et al. 2006).

We have alluded to the migratory capacity of HSCs in our discussion of the results of various transplantation experiments designed to validate the role of specific regulatory molecules. The interaction between stem cells and the microenvironment is fundamental in HSC functions that involve migration. From their genesis early in ontogeny, HSCs begin a journey that leads them through several locations in the developing embryo and eventually inside the bones to the marrow cavity, where they sustain hematopoiesis throughout adult life (Christensen et al. 2004, Ueno and Weissman 2006). Although these cells establish primary residence in the bone marrow of the adult, they have become well known for their ability to migrate. Under physiological conditions, HSCs can leave the bone marrow or mobilize into the peripheral blood and successfully re-enter the bone marrow microenvironment (Wright et al. 2001, Abkowitz JL et al. 2003). HSCs have also been reported to mobilize in response to injury or stress in nonhematopoietic tissue (Kollet et al. 2003). The migratory capacity of HSCs, however, is most apparent in the extreme conditions of clinical transplantation and mobilization.

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