Bone marrow-derived mononuclear cell therapy induces distal angiogenesis after local injection in critical leg ischemia

被引:77
作者
Van Huyen, Jean-Paul Duong [1 ,2 ,3 ,4 ]
Smadja, David M. [4 ,5 ,6 ]
Bruneval, Patrick [1 ,3 ,4 ]
Gaussem, Pascale [4 ,5 ,6 ]
Dal-Cortivo, Liliane [4 ,7 ,8 ]
Julia, Pierre [4 ,9 ]
Fiessinger, Jean-Noel [4 ,5 ,10 ]
Cavazzana-Calvo, Marina [4 ,7 ,8 ]
Aiach, Martine [4 ,5 ,6 ]
Emmerich, Joseph [4 ,5 ,10 ]
机构
[1] INSERM, UMRS 872, F-75908 Paris 15, France
[2] Serv Anat Pathol, F-75908 Paris 15, France
[3] Hop Europeen Georges Pompidou, Dept Pathol, Paris, France
[4] Univ Paris 05, Paris, France
[5] INSERM, U765, F-75654 Paris 13, France
[6] Hop Europeen Georges Pompidou, Hematol Haemostasis Lab, Paris, France
[7] Hop Necker Enfants Malad, Dept Biotherapies, Paris, France
[8] INSERM, U768, Paris, France
[9] Hop Europeen Georges Pompidou, Dept Cardiac & Vasc Surg, Paris, France
[10] Hop Europeen Georges Pompidou, Dept Vasc Med & Hypertens, Paris, France
关键词
angiogenesis; bone marrow mononuclear cells; cell therapy; ischemia; peripheral artery disease;
D O I
10.1038/modpathol.2008.48
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Critical leg ischemia is associated with a high risk of amputation when revascularization is not possible. Cell therapy based on bone marrow-derived mononuclear cells or with peripheral mononuclear cells, collected after stimulation with G-CSF has been used in an attempt to stimulate angiogenesis. Although several studies have raised the hope that such cell therapy may be effective in critical leg ischemia, no direct demonstration of angiogenesis induced by bone marrow-derived mononuclear cell/peripheral mononuclear cell injection has been reported in man. The aim of this study was to identify and to evaluate the extent of the angiogenic process associated with cell therapy in critical leg ischemia in man. To address this question, this pathological study was conducted in patients enrolled in the OPTIPEC clinical trial (Optimization of Progenitor Endothelial Cells in the Treatment of Critical leg ischemia), an interventional cell therapy study in critical leg ischemia. Amputation specimens from these patients were submitted to a standardized dissection protocol. In three patients, an active angiogenesis was observed in the distal part of the ischemic limb but not in the gastrocnemius muscle, the site of bone marrow cell injection. All the newly formed vessels were positive for endothelial cell markers (CD31, CD34, von Willebrand factor) and negative for markers of lymphatic vessels (podoplanin). Immunohistochemical staining for Ki-67 and c-kit showed extensive endothelial cell proliferation within the new vessels. Bone marrow-derived mononuclear cell therapy in patients with critical leg ischemia induces an active, substained angiogenesis in the ischemic and distal parts of the treated limb, although this may not prevent amputation in some patients with very severe ischemia.
引用
收藏
页码:837 / 846
页数:10
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