Mesenchymal progenitor cells localize within hematopoietic sites throughout ontogeny

Abstract

Mesenchymal stem cells (MSCs) have great clinical potential for the replacement and regeneration of diseased or damaged tissue. They are especially important in the production of the hematopoietic microenvironment,which regulates the maintenance and differentiation of hematopoietic stem cells (HSCs). In the adult, MSCs and their differentiating progeny are found predominantly in the bone marrow (BM). However, it is as yet unknown in which embryonic tissues MSCs reside and whether there is a localized association of these cells within hematopoietic sites during development. To investigate the embryonic origins of these cells, we performed anatomical mapping and frequency analysis of mesenchymal progenitors at several stages of mouse ontogeny. We report here the presence of mesenchymal progenitors, with the potential to differentiate into cells of the osteogenic, adipogenic and chondrogenic lineages, in most of the sites harboring hematopoietic cells. They first appear in the aorta-gonad-mesonephros (AGM) region at the time of HSC emergence. However, at this developmental stage, their presence is independent of HSC activity. They increase numerically during development to a plateau level found in adult BM. Additionally, mesenchymal progenitors are found in the embryonic circulation. Taken together, these data show a co-localization of mesenchymal progenitor/stem cells to the major hematopoietic territories, suggesting that, as development proceeds,mesenchymal progenitors expand within these potent hematopoietic sites.

Migration of dorsal aorta mesenchymal stem cells induced by mouse embryonic circulation

“…associated and could form a unique bone marrow niche (Mendez-Ferrer et al, 2010 Generally, there are three features of the mouse DA-MSC identified here. First, our result was different from previous results that mouse primary adherent cells derived from the E11 DA region lack the ability to differentiate into adipose lineage (Mendes et al, 2005). The DA-MSCs of mouse possessed the same adipogenic potential as those of human being, confirmed by oil red-O staining and specific adipogenic gene expression (Wang et al, 2008).…”

“…Mendes et al revealed the mesenchymal potential in E12-E14 circulation (Mendes et al, 2005). As shown in Figure 4, canonical MSCs were also detected in E12.5 and E13.5 embryonic circulation, they harbored typical morphology, immunophenotype and function.…”

“…By analyzing various organs (yolk sac, head, somites, limb buds, heart, liver, vitelline/umbilical arteries, and AGM) from E11 mouse embryos, Mendes et al were the first to find that the primary cells from the AGM region possessed intact mesenchymal (osteogenic, adipogenic, and chondrogenic) potential. Surprisingly, the primary cells from the mouse DA failed to generate adipocytes (Mendes et al, 2005). In line with this, Durand et al were unable to find the adipogenic potential in the immortalized stromal clones from the mouse DA (Durand et al, 2006).…”

“…They are also thought to translocate by means of the embryonic circulation to seed downstream hematopoiesis organs for further expansion and maturation. Of interest, the primary cells in the mouse circulation displayed mesenchymal potential (Mendes et al, 2005), with extremely low frequency and a narrow time-window (E12-E14). The fact that the mesenchymal cells in embryonic circulation emerged later than in the vascular bed suggested the migration of such cells as HSCs.…”

Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice

“…In particular, the maintenance of hematopoietic stem cells (HSCs) needs a specialized microenvironment called the 'niche' in the BM. [1][2][3] Various cellular components such as osteoblasts, 4,5,7 endothelial cells 6 and adipocytes 7,8 have been reported to support hematopoiesis. 9 Studies to trace transplanted HSCs show that BM HSCs reside close to the endosteal surface in the trabecula, and that hematopoietic differentiation proceeds readily toward the longitudinal axis of the marrow.…”