Placental growth factor-1 potentiates hematopoietic progenitor cell mobilization induced by granulocyte colony-stimulating factor in mice and nonhuman primates

Carmelo Carlo-Stella, Massimo Di Nicola, Paolo Longoni, Loredana Cleris, Cristiana Lavazza, Raffaella Milani, Marco Milanesi, Michele Magni, Virgilio Pace, Francesco Colotta, Maria A. Avanzini, Franca Formelli, Alessandro M. Gianni

Research output: Contribution to journalArticlepeer-review

Abstract

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 (rm-PlGF-2) and recombinant human PlGF-1 (rhPlGF-1). PBPC mobilization was evaluated by assaying colonyforming cells (CFCs), high-proliferative potential-CFCs (HPP-CFCs), and long-term culture-initiating cells (LTCICs). 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.

Original languageEnglish
Pages (from-to)252-261
Number of pages10
JournalStem Cells
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Granulocyte colony-stimulating factor
  • Placental growth factor
  • Stem cell mobilization
  • Stem cell transplantation

ASJC Scopus subject areas

  • Cell Biology

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