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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/H213    most recent 00112.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Voisine, P. Articles by Laham, R. J. Search for Related Content PubMed PubMed Citation Articles by Voisine, P. Articles by Laham, R. J.

Skin-derived microorgan autotransplantation as a novel approach for therapeutic angiogenesis

¹Divisions of Cardiology and Cardiac Surgery, Laval Hospital, Quebec City, Quebec, Canada; ²Beth Israel Deaconess Medical Center-Harvard Medical School, Boston, Massachusetts; ³Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel; and ⁴First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Submitted 28 January 2007 ; accepted in final form 10 September 2007

Despite promising preclinical results, transient single-factor-based therapeutic angiogenesis has shown no definitive benefits in clinical trials. The use of skin-derived microorgans (SMOs), capable of sustained expression of angiogenic factors and sustained viability with their cellular and extracellular elements, constitutes an attractive alternative. We sought to evaluate the efficacy of SMO implantation in a porcine model of chronic myocardial ischemia. Eighteen pigs underwent placement of an ameroid constrictor on the proximal circumflex artery. Three weeks later, split-thickness skin biopsies were harvested and pigs were randomized to lateral wall implantation of either 8 or 16 SMOs or blank injections. The procedure was safe and resulted in no adverse events. Three weeks after treatment, SMO implantation resulted in significant improvement of lateral wall perfusion during pacing, assessed by isotope-labeled microspheres [post- vs. pretreatment ratios of lateral/anterior wall blood flow were 1.31 ± 0.09 (SMOs) and 1.04 ± 0.06 (controls); P = 0.03]. No significant difference in angiographic scores was observed. Microvascular relaxation in response to VEGF was impaired in the ischemic territory of the control group but returned to normal after SMO implantation, indicating restoration of endothelial function. Molecular studies showed significant increases in VEGF and CD31 expression in the ischemic area of treated animals. Morphometric analysis showed increased neovascularization with SMO treatment. Autotransplantation of SMOs constitutes a novel approach for safe and effective therapeutic angiogenesis with improvement in perfusion, normalization of microvascular reactivity, and increased expression of VEGF and CD31.

growth factors; myocardial ischemia