Focusing on the borders between bone and blood to better understand stem cells based regeneration

It has been proposed that areas which border both bone and marrow contain specific niches which are crucial for hematopoietic stem cell (HSC) engraftment (Calvi LM, 2003). Similarly, we have shown that bone regeneration takes place after BM transplantation in discrete districts close to bone within the so called bone lining cells compartment where early osteopoietic engraftment originates as well (Dominici et al. 2004 and 2008). Very little is known about the mechanisms that drive the restoration of these compartments following a bone marrow (BM) injury. Researchers have been focused almost entirely on how HSCs are regulated by their microenvironmental niches (Zhang J 2003), with little attention paid to the recovery of cellular constituents of these niches after use of cytotoxic conditioning regimens. Moreover, while several models have been proposed, the precise anatomic location of niches within the BM microenvironment is not well understood. Thus, focusing on ionizing radiation (IR) exposure, we asked how the niches may respond to specific stress and affect mesenchymal engraftment as well. Based on this animal model, we report a profound disruption of the BM microenvironment after IR exposure that leads to a survival and generation of osteoblast constituting the niche (Dominici et al. 2009). These complex events are associated with a megakaryocytes re-location close to the bone lining cell compartment capable to stimulate osteoblasts which are then keen to host transplanted donor HSC. Thus, following irradiation, a hematopoietic cell lineage contributes to both skeletal turnover and to HSC osteoblast niche homeostasis. These results provide critical insights into the mechanisms of recovery of stem cell niches after BM radioablation, and suggest novel means to manipulate the BM microenvironment to promote HSC and bone engraftment.