Cytokine-induced osteopoietic differentiation of transplanted marrow cells

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...

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Bibliographic Details
Published in:Blood 2011-08, Vol.118 (8), p.2358-2361
Main Authors: Otsuru, Satoru, Rasini, Valeria, Bussolari, Rita, Hofmann, Ted J., Dominici, Massimo, Horwitz, Edwin M.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bone Marrow Cells - cytology
Bone Marrow Cells - drug effects
Bone Marrow Transplantation - pathology
Brief Report
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cytokines - pharmacology
Granulocyte Colony-Stimulating Factor - pharmacology
Growth Hormone - pharmacology
Hematologic and hematopoietic diseases
Hematopoiesis and Stem Cells
Medical sciences
Mice
Mice, Transgenic
Osteoblasts - cytology
Osteoblasts - drug effects
Osteocytes - cytology
Osteocytes - drug effects
Osteogenesis - drug effects
Osteogenesis - physiology
Parathyroid Hormone - pharmacology
Recombinant Proteins
Stem Cell Factor - pharmacology
Transplantation
Transplantation Chimera
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2011-01-331397