Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone

Carmelo Carlo-Stella, Massimo Di Nicola, Raffaella Milani, Paolo Longoni, Marco Milanesi, Carlo Bifulco, Claudio Stucchi, Anna Guidetti, Loredana Cleris, Franca Formelli, Gianni Garotta, Alesssandro M. Gianni

Research output: Contribution to journalArticlepeer-review


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. Materials and 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≤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 μg/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≤0.05), frequency of circulating CFCs per 105 mononuclear cells (36 vs 67, P≤0.009), as well as absolute numbers per mL of blood of circulating CFCs (783 vs 2288, P≤0.001) and LTC-IC (21 vs 64, P≤0.001). Conclusion. Our data demonstrate in mice that a 5-week treatment with rhGH restores age- and irradiation-associated loss of marrow primitive and committed progenitors.

Original languageEnglish
Pages (from-to)171-178
Number of pages8
JournalExperimental Hematology
Issue number2
Publication statusPublished - Feb 2004

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation


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