First trimester placental mesenchymal stem cells improve cardiac function of rat after myocardial infarction via enhanced neovascularization

Abstract

Acute myocardial infarction (AMI) is the most critical heart disease. Mesenchymal stem cells (MSCs) have been widely used as a therapy for AMI for several years. The human placenta has emerged as a valuable source of transplantable cells of mesenchymal origin that can be used for multiple cytotherapeutic purposes. However, the different abilities of first trimester placental chorion mesenchymal stem cells (FCMSCs) and third trimester placental chorion mesenchymal stem cells (TCMSCs) have not yet been explored. In this study, we aimed to compare the effectiveness of FCMSCs and TCMSCs on the treatment of AMI. FCMSCs and TCMSCs were isolated and characterized, and then they were subjected to in vitro endothelial cell (EC) differentiation induction and tube formation to evaluate angiogenic ability. Moreover, the in vivo effects of FCMSCs and TCMSCs on cardiac improvement were also evaluated in a rat MI model. Both FCSMCs and TCMSCs expressed a series of MSCs surface markers. After differentiation induction, FCMSCs-derived EC (FCMSCs-EC) exhibited morphology that was more similar to that of ECs and had higher CD31 and vWF levels than TCMSCs-EC. Furthermore, tube formation could be achieved by FCMSCs-EC that was significantly better than that of TCMSCs-EC. Especially, FCMSCs-EC expressed higher levels of pro-angiogenesis genes, PDGFD, VEGFA, and TNC, and lower levels of antiangiogenesis genes, SPRY1 and ANGPTL1. In addition, cardiac improvement, indicated by left ventricular enddiastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF), could be observed following treatment with FCMSCs, and it was superior to that of TCMSCs and Bone marrow MSCs (BMSCs). FCMSCs exhibited a superior ability to generate EC differentiation, as evidenced by in vitro morphology, angiogenic potential and in vivo cardiac function improvement; further, increased levels of expression of pro-angiogenesis genes may be the mechanism by which this effect occurred.

Patient-specific and gene-corrected induced pluripotent stem cell-derived endothelial cells elucidate single-cell phenotype of pulmonary veno-occlusive disease

“…It was speculated that the PI3K-Akt signaling pathway was the mainly disturbed pathway involved in the abnormal PVOD-iPSC-EC proliferation and angiogenesis ( Haque and Morris, 2017 ; Wang et al., 2013 ). Therefore, the expressions of downstream genes were detected, and it was found that the components of the PI3K-AKT signaling pathway evidently changed, and that PVOD-iPSC-ECs expressed higher levels of pro-proliferation (PCNA, MCM7, and MCM4) and pro-angiogenesis genes (PDGFD, VEGFA, and TNC), and lower levels of anti-angiogenesis gene ANGPTL1 ( Yu et al., 2021 ) ( Figure 4 C). Phospho-Akt/Total-Akt expression was upregulated in PVOD-iPSC-ECs, when compared with GC-PVOD-iPSC-ECs, indicating activation of the AKT signaling ( Figure 4 D).…”

Stem cell therapy for cardiac regeneration: key points

“…The study in rats with modeled myocardial infarction showed that transplantation of human placental stem cells improves the contractile function of the left ventricle, significantly reduces scar size, suppresses inflammation and apoptosis, and stimulates angiogenesis [199]. Additional processing of placental cells with hyaluronan ethers of oleic and retinoic acid, besides the pro-angiogenic effect, promotes their expression of cardiac markers connexin 43 and troponin I [179].…”

Applications of extraembryonic tissue-derived cells in vascular tissue regeneration

“…Moreover, fCMSCs exhibit significantly lower expression of antiangiogenic genes (SPRY1 and ANGPTL1) than tCMSCs. Additionally, the improvement in cardiac function achieved by fCMSCs is significantly greater than that achieved by treatment with both tCMSCs and BM-MSCs [ 61 ].…”