Insulin-like Growth Factor-1 (IGF-1) is a Costimulator of the Expansion of Lineage Committed Cells Derived from Peripheral Blood Mobilized CD34⁺ Cells in Multiple Myeloma Patients

Abstract

The effect of insulin-like growth factor-1 (IGF-1) on highly enriched human apheresis CD34⁺ progenitor cells was investigated in vitro. The progenitor cells were mobilized by treatment with cyclophosphamide + granulocyte—colony stimulating factor (G-CSF) in patients with multiple myeloma. CD34⁺ cells were cultured for 7 days in serumfree medium containing stem cell factor (SCF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), and this is referred to as cytokine-dependent proliferation. After 7 days of cytokine-dependent proliferation the total number of viable cells increased 1.6–8.2 times, and subsets of cells expressing the granulocyte marker CD15, the myelomonocytic marker CD64 and the erythrocyte phenotype CD71^high/CD64⁻ were detected among the in vitro cultured cells. Addition of G-CSF together with SCF + IL-3 + GM-CSF increased the number of CD15⁺ and CD64⁺ cells, but without altering the number of erythroid cells. IGF-1 caused a dose-dependent increase in the number of CD15⁺, CD64⁺ and CD71^high/CD64⁻ cells, and this increase was detected when cells were cultured in both SCF + IL-3 + GM-CSF alone and G-CSF + SCF + IL-3 + GM-CSF. A minor subset of CD34⁺ cells could still be detected among in vitro cultured cells and the number of CD34⁺ cells was not altered by adding G-CSF and/or IGF-1. Morphologically recognizable mature granulocytes or erythroid cells could not be detected for any of the combinations investigated. We conclude that IGF-1 can enhance the in vitro proliferation of committed progenitor cells derived from apheresis CD34⁺ cells.

Keywords:

• Insulin-like growth factor-1
• peripheral blood mobilized CD34⁺ cells
• multiple myeloma