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Войти в исследования The journal of gene medicine · 2009
Granulocyte-macrophage colony-stimulating factor gene based therapy for acute limb ischemia in a mouse model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sacramento Chester Bittencourt, Cantagalli Vanessa Dionisio, Grings Mariana, Carvalho Leonardo Pinto, Baptista-Silva José Carlos Costa, Beutel Abram, Bergamaschi Cassia Toledo, de Campos Junior Ruy Ribeiro, de Moraes Jane Zveiter, Takiya Christina Maeda, Samoto Vívian Yochiko, Borojevic Radovan, da Silva Flavia Helena, Nardi Nance Beyer, Dohmann Hans Fernando, Junior Hamilton Silva, Valero Valderez Bastos, Han Sang Won
Аннотация
BACKGROUND: Granulocyte-colony-stimulating factor (GM-CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM-CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases.
METHODS: A new mouse limb ischemia was established by surgery and gene transfer was performed by injection of 100 microg of a plasmid carrying GM-CSF. Muscle force and weight, histology, capillary density, circulating stem cells and monocytes were determined after 3-4 weeks.
RESULTS: More than 60% of nontreated ischemic animals showed gangrene below the heel after 4 weeks, whereas the GM-CSF gene-treated animals showed only darkening of nails or toes. These animals demonstrated a full recovery of the affected muscles in terms of weight, force and muscle fiber structure, but the muscles of nontreated ischemic animals lost approximately 50% weight, 86% force and their regular structure. When the GM-CSF gene was injected into the contralateral limb, only partial loss was observed, demonstrating a distant effect of GM-CSF. The capillary density in the GM-CSF-treated group was 52% higher in relation to the nontreated group. Blood analysis by flow cytometry showed that the GM-CSF-treated group had 10-20% higher levels of circulating monocytes and Sca-1(+).
CONCLUSIONS: We conclude that the direct administration of GM-CSF gene in limb ischemia had a strong therapeutic effect because it promoted the recovery of muscle mass, force and structure by mobilizing therapeutic cells and augmenting the number of vessels.
METHODS: A new mouse limb ischemia was established by surgery and gene transfer was performed by injection of 100 microg of a plasmid carrying GM-CSF. Muscle force and weight, histology, capillary density, circulating stem cells and monocytes were determined after 3-4 weeks.
RESULTS: More than 60% of nontreated ischemic animals showed gangrene below the heel after 4 weeks, whereas the GM-CSF gene-treated animals showed only darkening of nails or toes. These animals demonstrated a full recovery of the affected muscles in terms of weight, force and muscle fiber structure, but the muscles of nontreated ischemic animals lost approximately 50% weight, 86% force and their regular structure. When the GM-CSF gene was injected into the contralateral limb, only partial loss was observed, demonstrating a distant effect of GM-CSF. The capillary density in the GM-CSF-treated group was 52% higher in relation to the nontreated group. Blood analysis by flow cytometry showed that the GM-CSF-treated group had 10-20% higher levels of circulating monocytes and Sca-1(+).
CONCLUSIONS: We conclude that the direct administration of GM-CSF gene in limb ischemia had a strong therapeutic effect because it promoted the recovery of muscle mass, force and structure by mobilizing therapeutic cells and augmenting the number of vessels.