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 journalArticle

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. 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
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2004

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Human Growth Hormone
Growth Hormone
Bone Marrow
Cell Culture Techniques
Hematopoietic Stem Cell Mobilization
Stem Cells
Phosphates
Growth
Hematopoiesis
Granulocyte Colony-Stimulating Factor
Leukocyte Count
Bone Marrow Cells
Cytokines
Therapeutics

ASJC Scopus subject areas

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

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Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone. / Carlo-Stella, Carmelo; Di Nicola, Massimo; Milani, Raffaella; Longoni, Paolo; Milanesi, Marco; Bifulco, Carlo; Stucchi, Claudio; Guidetti, Anna; Cleris, Loredana; Formelli, Franca; Garotta, Gianni; Gianni, Alesssandro M.

In: Experimental Hematology, Vol. 32, No. 2, 02.2004, p. 171-178.

Research output: Contribution to journalArticle

Carlo-Stella, Carmelo ; Di Nicola, Massimo ; Milani, Raffaella ; Longoni, Paolo ; Milanesi, Marco ; Bifulco, Carlo ; Stucchi, Claudio ; Guidetti, Anna ; Cleris, Loredana ; Formelli, Franca ; Garotta, Gianni ; Gianni, Alesssandro M. / Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone. In: Experimental Hematology. 2004 ; Vol. 32, No. 2. pp. 171-178.
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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. 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.",
author = "Carmelo Carlo-Stella and {Di Nicola}, Massimo and Raffaella Milani and Paolo Longoni and Marco Milanesi and Carlo Bifulco and Claudio Stucchi and Anna Guidetti and Loredana Cleris and Franca Formelli and Gianni Garotta and Gianni, {Alesssandro M.}",
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T1 - Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone

AU - Carlo-Stella, Carmelo

AU - Di Nicola, Massimo

AU - Milani, Raffaella

AU - Longoni, Paolo

AU - Milanesi, Marco

AU - Bifulco, Carlo

AU - Stucchi, Claudio

AU - Guidetti, Anna

AU - Cleris, Loredana

AU - Formelli, Franca

AU - Garotta, Gianni

AU - Gianni, Alesssandro M.

PY - 2004/2

Y1 - 2004/2

N2 - 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.

AB - 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.

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