title: Cytokine-induced osteopoietic differentiation of transplanted marrow cells.
abstract: Transplantation of whole bone marrow (BMT) leads to engraftment of both osteoprogenitor cells and hematopoietic cells; however, the robust osteopoietic chimerism seen early after BMT decreases with time. Using our established murine model, we demonstrate that a post-BMT regimen of either granulocyte-colony stimulating factor, growth hormone, parathyroid hormone, or stem cell factor each stimulates greater donor osteoblast chimerism at 4 months posttransplantation than saline-treated controls and approximates the robust osteopoietic chimerism seen early after BMT; however, only growth hormone led to significantly more donor-derived osteocytes than controls. Importantly, there were no adverse hematologic consequences of the different treatments. Our data demonstrate that these cytokines can stimulate the differentiation of transplanted donor marrow cells into the osteopoietic lineage after BMT. Post-BMT cytokine therapy may generate durable osteopoietic engraftment, which should lead to sustained clinical benefit and render BMT more applicable to bone disorders.
authors.affiliation: Division of Oncology/Blood and Marrow Transplantation, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Satoru
authors.initials: S
authors.lastname: Otsuru
authors.forename: Valeria
authors.initials: V
authors.lastname: Rasini
authors.forename: Rita
authors.initials: R
authors.lastname: Bussolari
authors.forename: Ted J
authors.initials: TJ
authors.lastname: Hofmann
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 / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology; D011994:Recombinant Proteins; D019089:Stem Cell Factor / Q000494:pharmacology; D018183:Transplantation Chimera
chemical_list: D016207:Cytokines; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D013006:Growth Hormone