Effects of granulocyte-colony stimulating factor on bone marrow-derived progenitor cells in murine cardiac transplantation

Abstract

Granulocyte-colony stimulating factor (G-CSF) mobilizes progenitors from the bone marrow (BM) and into the circulation. In cardiac transplantation, G-CSF pretreatment of both donors and recipients has been found to improve cardiac function. The aim of this study was to examine whether the observed benefit of G-CSF pretreatment in cardiac transplantation involves vascular repopulation by host progenitor cells. Progenitor cells were exposed to immunosuppressive agents±G-CSF. The effect of drug treatment on total cell counts, proliferation, angiogenesis, apoptosis, and tubule formation was assessed. C57BL/6BM-GFP chimeric recipients underwent cardiac transplantation. Host progenitor cell seeding was evaluated on hearts 14 and 30 days post-transplant. G-CSF treatment of BM-derived progenitor cells in vitro improved survival, proliferation, and angiogenesis of the cells despite treatment with immunosuppressive agents. G-CSF pretreatment of BM-GFP transgenic recipient mice prior to heart transplantation resulted in increased re-endothelialization at 30 days post-transplant in G-CSF pretreated allografts (9.3±2.2%) relative to nonpretreated allografts (3.4±1.6%). G-CSF pretreated allografts also demonstrated a reduction of intimal narrowing in vessels of the transplanted heart. These findings suggest that G-CSF pretreatment leads to elevated numbers of host progenitor cells which may contribute to reconstitution of damaged allograft blood vessels.