Perspective: fundamental and clinical concepts on stem cell homing and engraftment: a journey to niches and beyond  Peter J. Quesenberry, Gerald Colvin, Mehrdad Abedi  Experimental Hematology  Volume 33, Issue 1, Pages 9-19 (January 2005) DOI: 10.1016/j.exphem.2004.10.012 Copyright © 2005 International Society for Experimental Hematology Terms and Conditions

Figure 1 Stem cell homing after intravenous injection. After injection (A), the stem cells leave the vascular space and enter the trabecular marrow compartments from central marrow vessels. Once in this space, there is subsequent localization within the bone marrow according to the phenotype of the cells. Stem cells demonstrate selective redistribution to the endosteal region. Taking a closer look at the vascular space within marrow is depicted in (B). The donor (D) and host (H) cells travel through marrow vessels and sinusoids. Adhesion receptors such as VCAM-1, P- and E-selectins and others on the stem cells are responsible for the initial process of endothelial migration. This occurs by the “stickiness” of the cell, by rolling, crawling, and then migrating into the extravascular marrow stromal space. The cells find their respective niche in stromal (S) cells by additional cell receptors. Note the open spaces within the marrow cavity. Stem cells are not static, they leave the marrow stroma and go out into the circulation. Proteopodal extensions may be the mechanism of how the cells home to their respective marrow niche. Experimental Hematology 2005 33, 9-19DOI: (10.1016/j.exphem.2004.10.012) Copyright © 2005 International Society for Experimental Hematology Terms and Conditions

Figure 2 Hematopoietic stem cell. Murine lineage-negative, rhodamine-lowt Hoechs-low marrow stem cell. Shows cytokine (steel factor and SDF-1) induced membrane protrusions termed proteopods. From Frimberger AE, McAuIiffe CI, Werme KA. et al. The fleet feet of haematopoietic stem cells: rapid motility, interaction and proteopodia. Br J Haematol 2001; 112:644-654 [77]. Reprinted with permission from Blackwell Publishing. Experimental Hematology 2005 33, 9-19DOI: (10.1016/j.exphem.2004.10.012) Copyright © 2005 International Society for Experimental Hematology Terms and Conditions

Figure 3 Theoretical and experimental syngeneic nonmyeloablative transplant. Theoretical engraftment with replacement or augmentation models compared to observed engraftrngit. A total of 72 unperturbed 6-to-8-week-old female BALB/c mice were injected with 40×106 male whole marrow cells, as controls for other experiments. The mean engraftment by fluorescence in situ hybridization was found to be 6.91±0.4%, which fits closely with the stem cell competition hypothesis. This indicates that syngeneic engraftment is determined by stem cell competition. Experimental Hematology 2005 33, 9-19DOI: (10.1016/j.exphem.2004.10.012) Copyright © 2005 International Society for Experimental Hematology Terms and Conditions