Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone.
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.
Carlo-Stella
Carmelo
C
"Cristina Gandini" Medical Oncology Unit, Istituto Nazionale Tumori, Milano, Italy. carmelo.carlostella@unimi.it
Di Nicola
Massimo
M
Milani
Raffaella
R
Longoni
Paolo
P
Milanesi
Marco
M
Bifulco
Carlo
C
Stucchi
Claudio
C
Guidetti
Anna
A
Cleris
Loredana
L
Formelli
Franca
F
Garotta
Gianni
G
Gianni
Alessandro M
AM
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
D013006:Growth Hormone