Open AccessPlacental Growth Factor‐1 Potentiates Hematopoietic Progenitor Cell Mobilization Induced by Granulocyte Colony‐Stimulating Factor in Mice and Nonhuman Primates
Author(s) -
CarloStella Carmelo,
Di Nicola Massimo,
Longoni Paolo,
Cleris Loredana,
Lavazza Cristiana,
Milani Raffaella,
Milanesi Marco,
Magni Michele,
Pace Virgilio,
Colotta Francesco,
Avanzini Maria A.,
Formelli Franca,
Gianni Alessandro M.
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0020
Subject(s) - granulocyte colony stimulating factor , haematopoiesis , progenitor cell , biology , placental growth factor , hematopoietic growth factor , medicine , mobilization , growth factor , endocrinology , granulocyte , recombinant dna , andrology , immunology , stem cell , cancer research , receptor , chemotherapy , vascular endothelial growth factor , microbiology and biotechnology , biochemistry , history , archaeology , vegf receptors , gene
The complex hematopoietic effects of placental growth factor (PlGF) prompted us to test in mice and nonhuman primates the mobilization of peripheral blood progenitor cells (PBPCs) elicited by recombinant mouse PlGF‐2 (rmPlGF‐2) and recombinant human PlGF‐1 (rhPlGF‐1). PBPC mobilization was evaluated by assaying colony‐forming cells (CFCs), high‐proliferative potential‐CFCs (HPP‐CFCs), and long‐term culture‐initiating cells (LTC‐ICs). In mice, both rmPlGF‐2 and rhPlGF‐1 used as single agents failed to mobilize PBPCs, whereas the combination of rhPlGF‐1 and granulocyte colony‐stimulating factor (rhG‐CSF) increased CFCs and LTC‐ICs per milliliter of blood by four‐ and eightfold, respectively, as compared with rhG‐CSF alone. rhPlGF‐1 plus rhG‐CSF significantly increased matrix metalloproteinase‐9 plasma levels over rhG‐CSF alone, suggesting a mechanistic explanation for rhPlGF‐1/rhG‐CSF synergism. In rhesus monkeys, rhPlGF‐1 alone had no mobilization effect, whereas rhPlGF‐1 (260 μg/kg per day) plus rhG‐CSF (100 μg/kg per day) increased rhG‐CSF‐elicited mobilization of CFCs, HPP‐CFCs, and LTC‐ICs per milliliter of blood by 5‐, 7‐, and 15‐fold, respectively. No specific toxicity was associated with the administration of rhPlGF‐1 alone or in combination. In conclusion, our data demonstrate that rhPlGF‐1 significantly increases rhG‐CSF‐elicited hematopoietic mobilization and provide a preclinical rationale for evaluating rhPlGF‐1 in the clinical setting.