Mesenchymal Stem Cells Genetically Modified with the Angiopoietin-1 Gene Enhanced Arteriogenesis in a Porcine Model of Chronic Myocardial Ischaemia

Abstract

The direct injection by thoracoscope of mesenchymal stem cells (MSCs) that had been genetically modified to express angiopoietin-1 was investigated in a porcine model to determine their effect on arteriogenesis and the effectiveness of this technique. Chronic myocardial ischaemia was established using a thoracoscope to insert an ameroid constrictor around the left circumflex coronary artery. Six weeks after establishing the ischaemia, 20 pigs were randomly divided into three groups to receive injections by thoracoscope of either genetically-modified MSCs, unmodified MSCs or phosphate-buffered saline into the ischaemic border area. The injections were repeated 1 month later. The genetically modified MSCs were found to restore blood flow significantly more than the other observed treatments and immunohistochemical evaluation of arteriogenesis supported this finding. In conclusion, the injection of MSCs that had been genetically modified to express angiopoietin-1 improved arteriogenesis and increased collateral blood flow in the myocardial ischaemic area. Thoracoscope delivery of the injection was safe and minimally invasive.

Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction

“…6 Moreover, histological findings confirmed the reduction of fibrosis in the infarct area (Figure 6), which is an important indicator for improved heart function since late reperfusion of infarcted vascular beds attenuates left ventricular remodeling including infarct expansion. 4 Measurement of blood flow using cardiac magnetic resonance imaging-based techniques can give a better real time picture on the progress of such myocardial regenerative process post cell transplantation.…”

“…[4][5][6] However, the mammalian gene delivery vectors widely used in such studies have various drawbacks and severe safety concerns. [7][8][9] These vectors are prone to integration into coding regions of transcriptionally active genes, raising concerns about gene silencing and insertional mutagenesis.…”

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

“…No autopsy was performed on these animals considering that the incidence of sudden cardiac deaths attributable to fibrillation or massive myocardial infarction can reach up to 30%, particularly during the period of ameroid closure. [27][28][29] All remaining pigs (25 in total) completed the study protocol. Unless otherwise specified, findings are reported for the LCx territory.…”

Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

“…Hepatocyte growth factor-overexpressing MSCs injected into a rat heart after an infarct increased the density of capillaries and reduced the area of damage (Duan et al, 2003). Similarly, MSCs expressing angiopoietin have protective effects in both cerebral (Onda et al, 2008) and myocardial (Sun et al, 2007;Chen et al, 2009) models. In the cerebral artery occlusion model intravenous delivery of angiopoietin-expressing MSCs increased angiogenesis around the border of the lesion but had little or no effect on lesion volume (Onda et al, 2008).…”