title: Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone.
abstract: OBJECTIVE
  The aim of this story was to evaluate the activity of recombinant human (rh) growth hormone (GH) in restoring bone marrow progenitor cell growth as well as cytokine-elicited stem cell mobilization in aged BALB/c mice with impaired marrow hematopoietic function and reduced stem cell mobilizing capacity.
  
  
  METHODS
  BALB/c mice included in this study were either naturally aged (group I) or aged after having been used for radioprotective assays (group II). Mice were treated for 5 weeks with either rhGH [2.5 mg/kg/day intraperitoneally (IP)] or phosphate-buffered saline (PBS). Subsequently, colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) were evaluated. In addition, progenitor cell mobilization elicited by granulocyte colony-stimulating factor (rhG-CSF) was analyzed.
  
  
  RESULTS
  Compared with young controls, the growth of marrow CFCs and LTC-ICs was significantly reduced (P < or = 0.05) in group I and II mice. Treatment with rhGH significantly enhanced marrow hematopoiesis in mice of both groups, as demonstrated by a complete restoration of marrow cellularity, and CFC and LTC-IC growth. To further evaluate the hematopoietic potential of rhGH, aged mice treated with rhGH or PBS were mobilized with rhG-CSF (10 microg/day IP for 5 days). Compared with PBS-injected mice, rhGH-treated mice showed a significant improvement of rhG/CSF-elicited stem cell mobilization, with significant increases of white blood cell counts (5633 vs 8133, P < or = 0.05), frequency of circulating CFCs per 10(5) mononuclear cells (36 vs 67, P < or = 0.009), as well as absolute numbers per mL of blood of circulating CFCs (783 vs 2288, P < or = 0.001) and LTC-IC (21 vs 64, P < or = 0.001).
  
  
  CONCLUSIONS
  Our data demonstrate in mice that a 5-week treatment with rhGH restores age- and irradiation-associated loss of marrow primitive and committed progenitors.
authors.affiliation: "Cristina Gandini" Medical Oncology Unit, Istituto Nazionale Tumori, Milano, Italy. carmelo.carlostella@unimi.it
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Raffaella
authors.initials: R
authors.lastname: Milani
authors.forename: Paolo
authors.initials: P
authors.lastname: Longoni
authors.forename: Marco
authors.initials: M
authors.lastname: Milanesi
authors.forename: Carlo
authors.initials: C
authors.lastname: Bifulco
authors.forename: Claudio
authors.initials: C
authors.lastname: Stucchi
authors.forename: Anna
authors.initials: A
authors.lastname: Guidetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Cleris
authors.forename: Franca
authors.initials: F
authors.lastname: Formelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Garotta
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
mesh_terms: D000367:Age Factors; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D013006:Growth Hormone