title: The relationship between bone, hemopoietic stem cells, and vasculature.
abstract: A large body of evidence suggests hemopoietic stem cells (HSCs) exist in an endosteal niche close to bone, whereas others suggest that the HSC niche is intimately associated with vasculature. In this study, we show that transplanted hemopoietic stem and progenitor cells (HSPCs) home preferentially to the trabecular-rich metaphysis of the femurs in nonablated mice at all time points from 15 minutes to 15 hours after transplantation. Within this region, they exist in an endosteal niche in close association with blood vessels. The preferential homing of HSPCs to the metaphysis occurs rapidly after transplantation, suggesting that blood vessels within this region may express a unique repertoire of endothelial adhesive molecules. One candidate is hyaluronan (HA), which is highly expressed on the blood vessel endothelium in the metaphysis. Analysis of the early stages of homing and the spatial dis-tribution of transplanted HSPCs at the single-cell level in mice devoid of Has3-synthesized HA, provides evidence for a previously undescribed role for HA expressed on endothelial cells in directing the homing of HSPCs to the metaphysis.
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Ellis
authors.forename: Jochen
authors.initials: J
authors.lastname: Grassinger
authors.forename: Allan
authors.initials: A
authors.lastname: Jones
authors.forename: Judy
authors.initials: J
authors.lastname: Borg
authors.forename: Todd
authors.initials: T
authors.lastname: Camenisch
authors.forename: David
authors.initials: D
authors.lastname: Haylock
authors.forename: Ivan
authors.initials: I
authors.lastname: Bertoncello
authors.forename: Susan K
authors.initials: SK
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D001853:Bone Marrow / Q000098:blood supply*; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D005269:Femur / Q000166:cytology / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D055153:Stem Cell Niche / Q000098:blood supply / Q000166:cytology; D057705:Transendothelial and Transepithelial Migration; D055114:X-Ray Microtomography
chemical_list: D015815:Cell Adhesion Molecules; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491356:Has3 protein, mouse; D000076002:Hyaluronan Synthases