Abstract
Objective:
Post-angioplasty restenosis due to neointima formation has been attributed to the inflammatory response after acute endoluminal injury. ST266 (Noveome Biotherapeutics, Inc.) a novel secretome derived from proprietary GMP-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 ST266 in a rat arterial balloon angioplasty model.
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, animals in ST266 groups received 0.1, 0.5 or 1ml IV ST266 q.d. In the systemic AMP groups, single-dose (SD) of 0.5 million (M) or 1 M AMPs was injected via Inferior Vena Cava after the angioplasty. In AMP implant experiment 1 M, 5 M or 20 M 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.
Results:
1ml ST266 decreased Neointima/Neointima+Media ratio (N/NM) compared to noTx group (0.34±0.01 vs 0.54±0.04 resp.;
p
=0.004). ST266 also decreased Luminal Stenosis (LS) compared to noTx group (18.18±1.86 vs 39.23±5.75%;
p
=0.008). SD 1 M AMPs decreased LS compared to noTx group (39.23±5.75 vs 19.50±5.35%;
p
=0.033). Significant differences in N/NM were found between 20 M implanted AMPs and noTx group (0.35±0.02 vs 0.54±0.04 resp.;
p
=0.003) and the MTG-only group (0.53±0.05,
p
=0.007). 20 M implanted AMPs decreased the LS (16.78±2.47%) compared to both noTx (39.23±5.75%,
p
=0.001) and MTG-only groups (37.51±8.55%,
p
=0.016). 1ml ST266 significantly increased the re-endothelialization index 10 days after balloon angioplasty compared to noTx group (0.40±0.04 vs 0.14±0.037% resp.,
p
=0.002).
Conclusion:
ST266 reduces neointima formation and luminal stenosis and increases the re-endothelialization index after balloon angioplasty. Further research to elucidate the underlying mechanisms is ongoing.