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

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. Crown Copyright (c) 2010 Published by Elsevier Inc. All rights reserved.