Impact of Angiogenic Therapy in the Treatment of Critical Lower Limb Ischemia in an Animal Model

Paulo Eduardo Ocke Reis, Leonardo Pinto de Carvalho, Eduardo Yasumura, Flavia Helena da Silva, Bianca Cristina Garcia, Abram Beutel, Chester Bittencourt Sacramento, José Carlos Costa Baptista-Silva, Ruy Ribeiro de Campos, Christina Maeda Takiya, Radovan Borojevic, Sang Won Han
  • Vascular and Endovascular Surgery, January 2014, SAGE Publications
  • DOI: 10.1177/1538574413518119

Impact of Angiogenic Therapy in the Treatment of Critical Lower Limb Ischemia in an Animal Model

What is it about?

Angiogenic therapies for critical limb ischemia were tested in a mouse model. The mice were anesthetized and their femoral arteries were ligated. The animals were treated with bone marrow mononuclear cells (BMMCs) alone, BMMCs combined with plasmid vector encoding granulocyte macrophage colony-stimulating factor (GM-CSF), received no treatment, or no intervention (controls). The degree of ischemia was monitored for 4 weeks using a visual scale. Muscle atrophy and strength were assessed at 4 weeks postoperatively; the mice were then killed. In treated animals, total necrosis of the limb was not found, the weight of the gastrocnemius and quadriceps muscles was significantly higher, functional ability and tissue regeneration were significantly increased, and muscle impairment and adipocyte presence were significantly reduced compared with untreated animals. At inducing angiogenesis, the BMMCs alone was more effective than BMMCs combined with plasmid vector encoding GM-CSF. Treated animals showed increased angiogenesis compared with ischemic untreated ones.

Why is it important?

Treated animals showed increased angiogenesis compared with ischemic untreated ones. Keywords ischemia, lower extremity, cell therapy, gene therapy, angiogenesis-inducing agents

Perspectives

Professor Paulo Eduardo Ocke Reis
Universidade Federal Fluminense

In the study model, both treatments (BMMCs alone and BMMCs combined with plasmid vector encoding GM-CSF) resulted in therapeutic benefits in ischemic limbs. Our results revealed that cell therapy alone was more effective than the combined used of cell and gene therapy at inducing angiogen- esis. The clinical outcomes in groups treated with angiogenic therapy were better than those observed in the untreated group, indicating the safety and efficacy of the therapies in an experi- mental model of peripheral arterial ischemia. These findings suggest that angiogenic therapy may be a source of hope for patients with severe, extensive PAOD and reduced vascular bed, and for whom all other therapeutic options have been exhausted.

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http://dx.doi.org/10.1177/1538574413518119

The following have contributed to this page: Professor Paulo Eduardo Ocke Reis