S. Rahimpour1, X. Liu2, X. Wang2, R. Banas3, S. M. Pham1 3Noveome Biotherapeutic, Inc.,Pittsburgh, PA, USA 1Mayo Clinic – Florida,Cardiothoracic Surgery,Jacksonville, FL, USA 2University Of Maryland,Surgery,Baltimore, MD, USA
Introduction: Inflammation plays an essential role in post-angioplasty neointima formation and in-stent restenosis. ST266 (Noveome Biotherapeutics, Inc.) a novel secretome derived from cultured human Amnion-Derived Multipotent Progenitor (AMP) cells, has been shown to be anti-inflammatory and to promote wound healing. This study examined the therapeutic potential of AMP cells and ST266 in a post balloon-angioplasty arterial restenosis model in rats.
Methods: Animals were randomly divided in the following groups (N=7): no-treatment (noTx), systemic ST266, systemic AMPs and local AMP implants. Neointima hyperplasia was induced in the iliac artery of Sprague-Dawley male rats using a 2F Fogarty embolectomy catheter. After surgery, the animals in ST266 groups received 0.1, 0.5 or 1ml IV ST266 daily. In the systemic AMP groups, single-dose (SD) of 0.5 million (M) or 1.0M AMPs was injected via inferior vena cava after the angioplasty. In local AMP experiment 1M, 5M or 20M AMPs were implanted in 300 µL Matrigel (MTG) around the iliac artery after balloon angioplasty.
28 days after the surgery, the iliac arteries were removed for histologic analysis. Re-endothelialization index was measured 10 days after balloon angioplasty. We also performed Smooth Muscle Cell (SMC) migration and proliferation assay and Western Blot for SIRT1 expression.
Results: Compared to noTx group, ST266 (1 ml) group decreased Neointima/Neointima+Media ratio (N/NM) (0.34±0.01 vs 0.54±0.04; p=0.004), and luminal stenosis (LS) (18.18±1.86 vs 39.23±5.75%; p=0.008). AMPs (at 1M dose) decreased LS compared to noTx group (18.56 ± 2.50 vs 35.92 ± 5.75; p=0.006). Significant reduction in N/NM were found between implanted AMPs (at 20 M cell dose) and noTx groups (0.35±0.02 vs 0.54±0.04; p=0.003) and the MTG-only group (0.53±0.05, p=0.007). 20M implanted AMPs decreased the LS (16.78±2.47%) compared to the both noTx (39.23±5.75%, p=0.001) and MTG-only groups (37.51±8.55%, p=0.016). ST266 (at 1 ml dose) significantly increased the re-endothelialization index compared to noTx group (0.40±0.04 vs 0.14±0.037, p=0.002). SIRT1 expression significantly increased in SMCs 24 hrs. after treatment with 40% ST266 compared to SMC growth media and PBS (4.22 ± 0.23 vs 1.90 ± 0.17 and 2.56 ± 0.62, p=0.005).
Conclusion:ST266 reduces neointima formation and luminal stenosis after balloon angioplasty. It is a potential novel therapeutic agent to prevent vascular restenosis in human.
