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

• Published in: Cardiovascular pathology 2010, Vol.19 (1), p.36-47
• Main Authors: Rezai, Nana, Deisher, Theresa A, Heine, Heather L, Wang, Xiaozhen, Corbel, Stephane Y, Leung, Joanna, Kerjner, Alexandra, Rossi, Fabio M.V, Podor, Thomas J, McManus, Bruce M
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Bone marrow; Bone Marrow Cells - drug effects; Cell Separation; Coronary Vessels - drug effects; Flow Cytometry; Fluorescent Antibody Technique; G-CSF; Granulocyte Colony-Stimulating Factor - pharmacology; Heart; Heart Transplantation; Hematopoietic Stem Cells - drug effects; Humans; Immunosuppressive Agents - pharmacology; Mice; Mice, Transgenic; Microscopy, Confocal; Neovascularization, Physiologic; Pathology; Stem cell; Tacrolimus - pharmacology; Transplantation
• ISSN: 1054-8807; 1879-1336
• DOI: 10.1016/j.carpath.2008.10.007

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.