Hematopoietic stem cell lodgment in the adult bone marrow stem cell niche.
Treatment of malignant blood disorders, such as leukemia, that can provide a better chance of long-term remission involves myeloablation followed by transplantation of matched donor hematopoietic stem cells (HSCs). For successful engraftment and re-establishment of hematopoiesis to occur in the recipient, the transplanted HSCs must first migrate from the blood circulation to the bone marrow (BM), a process known as homing, then localize and anchor in suitable microenvironments within the BM, a process known as lodgment. After lodgment, the specific fate of the transplanted HSCs is determined through complex, bidirectional interactions with various stromal cell components in the niche. Ultimately, these interactions dictate the clinical outcome of the transplantation. Through the use of transgenic mouse models, considerable evidence has been accumulated in an attempt to unveil the possible underlying mechanisms that govern these processes. Here, we will emphasize the major factors that are involved in the regulation of lodgment of transplanted HSCs. Specifically, we will first introduce early observations on the spatial distribution of hematopoietic progenitors within the BM, then we will discuss the soluble factors, chemokines, cell-cell interactions, and cell-matrix interactions that have been studied and known to influence the site of HSC lodgment within the BM following transplantation.
Lam
B S
BS
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Adams
Gregor B
GB
D000818:Animals; D001853:Bone Marrow; D015815:Cell Adhesion Molecules / Q000502:physiology; D054377:Chemokine CXCL12 / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D019718:Receptors, CXCR4 / Q000502:physiology; D055153:Stem Cell Niche / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology
C514936:CXCR4 protein, mouse; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4