Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor

Abstract

Mesenchymal stem cells could differentiate into cardiomyocytes in vitro and have been shown to reconstitute the impaired myocardium in vivo. Hepatocyte growth factor, a recognized angiogenic factor and endothelial cell chemoattractant, has been applied in the treatment of myocardial ischemia. In this study, we used a ligation model of proximal left anterior descending coronary artery of rats to evaluate the effect of mesenchymal stem cells overexpressing hepatocyte growth factor in the treatment of myocardial ischemia. Bone marrow-derived mesenchymal stem cells were isolated, expanded, characterized, and infected with adenovirus carrying human hepatocyte growth factor cDNA (Ad-HGF). Mesenchymal stem cells infected by Ad-HGF released soluble HGF protein at a high level, which was maintained at least for 2 weeks. Implantation of mesenchymal stem cells overexpressing hepatocyte growth factor into left anterior descending risk areas improved the functions of impaired myocardium, including diminishing the area of ischemia, increasing the number of capillaries, and reducing collagen content. By using the sry gene as a marker, we also demonstrated that the engrafted cells or their progeny incorporated into ischemic cardiac muscle. These results showed that treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor could be a novel strategy that can both restore local blood flow and regenerate lost cardiomyocytes.

Assessment of the green florescence protein labeling method for tracking implanted mesenchymal stem cells

“…The sensitivity and relative simplicity of GFP detection make it appealing. At present, GFP has already been used as an agent for tracking SCs (Duan et al 2003;Xu et al 2010); however, little information is known about the retention of injected GFP-labeled cells implanted in the ischemic heart over time.…”

“…The medium containing 10% FBS was removed prior to transduction. The Ad-GFP (a gift from Chinese Academy of Military Medical Sciences) (Duan et al 2003;Lu et al 2006) was then added along with 200 lL of serum-free medium, and the flask was shaken gently every 15 min for 2 h. The passage 5 BM-MSCs were transduced with the recombinant replicationdefective adenovirus at different multiplicities of infection (MOI) in the range 0-200 units. After incubation with Ad-GFP for 2 h, culture medium containing 10% FBS was added into the flask.…”

Effect of Mini‐Tyrosyl‐tRNA Synthetase/Mini‐Tryptophanyl‐tRNA Synthetase on Angiogenesis in Rhesus Monkeys after Acute Myocardial Infarction

“…Adenoviral vectors constructed for previous experiments were used in this study [21]. Four weeks after the ligation of the LAD, the animals were randomly divided into four groups (n = 44): ad-mini-TyrRS-injected group (ad-mini-TyrRS group, n = 11), admini-TrpRS-injected group (ad-mini-TrpRS group, n = 11), adnull-injected group (ad-null, n = 11), and HEPES saline-injected group (saline, n = 11).…”

The efficacy of MSC-HGF in treating pulmonary arterial hypertension (PAH) and connexin remodelling

“…The HGF construct (Ad-HGF) was made by the Chinese Academy of Military Medical Sciences and is a replication-deficient recombinant adenovirus vector carrying human HGF [14,15]. The mesenchymal stem cells were infected with the recombinant replicationdefective adenovirus at different m.o.i.…”