title: Delayed marrow infusion in mice enhances hematopoietic and osteopoietic engraftment by facilitating transient expansion of the osteoblastic niche.
abstract: Transplantation of bone marrow cells leads to engraftment of osteopoietic and hematopoietic progenitors. We sought to determine whether the recently described transient expansion of the host osteoblastic niche after marrow radioablation promotes engraftment of both osteopoietic and hematopoietic progenitor cells. Mice infused with marrow cells 24 hours after total body irradiation (TBI) demonstrated significantly greater osteopoietic and hematopoietic progenitor chimerism than did mice infused at 30 minutes or 6 hours. Irradiated mice with a lead shield over 1 hind limb showed greater hematopoietic chimerism in the irradiated limb than in the shielded limb at both the 6- and 24-hour intervals. By contrast, the osteopoietic chimerism was essentially equal in the 2 limbs at each of these intervals, although it significantly increased when cells were infused 24 hours compared with 6 hours after TBI. Similarly, the number of donor phenotypic long-term hematopoietic stem cells was equivalent in the irradiated and shielded limbs after each irradiation-to-infusion interval but was significantly increased at the 24-hour interval. Our findings indicate that a 24-hour delay in marrow cell infusion after TBI facilitates expansion of the endosteal osteoblastic niche, leading to enhanced osteopoietic and hematopoietic engraftment.
authors.affiliation: Division of Oncology/Blood and Marrow Transplantation, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Roberta
authors.initials: R
authors.lastname: Marino
authors.forename: Satoru
authors.initials: S
authors.lastname: Otsuru
authors.forename: Ted J
authors.initials: TJ
authors.lastname: Hofmann
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Olson
authors.forename: Valeria
authors.initials: V
authors.lastname: Rasini
authors.forename: Elena
authors.initials: E
authors.lastname: Veronesi
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.forename: Mostafa Waleed
authors.initials: MW
authors.lastname: Gaber
authors.forename: Caridad
authors.initials: C
authors.lastname: Martinez
authors.forename: Paolo
authors.initials: P
authors.lastname: Paolucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D014182:Transplantation, Autologous
keywords: Bone marrow transplantation; Donor-derived osteopoiesis; Osteoblastic niche