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

Pierre Voisine, Audrey Rosinberg, Joanna J. Wykrzykowska, Yulia Shamis, Fu Wu Gui, Evan Appelbaum, Jian Li, Frank W. Sellke, Duane Pinto, C. Michael Gibson, Eduardo Mitrani, Roger J. Laham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)H213-H219
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Growth factors
  • Myocardial ischemia

Fingerprint

Dive into the research topics of 'Skin-derived microorgan autotransplantation as a novel approach for therapeutic angiogenesis'. Together they form a unique fingerprint.

Cite this