Impact of Myocardial Infarct Proteins and Oscillating Pressure on the Differentiation of Mesenchymal Stem Cells: Effect of Acute Myocardial Infarction on Stem Cell Differentiation

Abstract

Stem cell transplantation in acute myocardial infarction (AMI) has emerged as a promising therapeutic option. We evaluated the impact of AMI on mesenchymal stem cell (MSC) differentiation into cardiomyocyte lineage. Cord blood-derived human MSCs were exposed to in vitro conditions simulating in vivo environments of the beating heart with acute ischemia, as follows: (a) myocardial proteins or serum obtained from sham-operated rats, and (b) myocardial proteins or serum from AMI rats, with or without application of oscillating pressure. Expression of cardiacspecific markers on MSCs was greatly induced by the infarcted myocardial proteins, compared with the normal proteins. It was also induced by application of oscillating pressure to MSCs. Treatment of MSCs with infarcted myocardial proteins and oscillating pressure greatly augmented expression of cardiac-specific genes. Such expression was blocked by inhibitor of transforming growth factor ␤ 1 (TGF-␤ 1 ) or bone morphogenetic protein-2 (BMP-2). In vitro cellular and electrophysiologic experiments showed that these differentiated MSCs expressing cardiomyocytespecific markers were able to make a coupling with cardiomyocytes but not to selfbeat. The pathophysiologic significance of in vitro results was confirmed using the rat AMI model. The protein amount of TGF-␤ 1 and BMP-2 in myocardium of AMI was significantly higher than that in normal myocardium. When MSCs were transplanted to the heart and analyzed 8 weeks later, they expressed cardiomyocyte-specific markers, leading to improved cardiac function. These in vitro and in vivo results suggest that infarctrelated biological and physical factors in AMI induce commitment of MSCs to cardiomyocyte-like cells through TGF-␤/BMP-2 pathways.

Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model

“…By virtue of these properties, pre-clinical trials with hUCB-MSCs have been conducted in the contexts of Alzheimer’s disease [7], myocardial infarction [8], stroke [9] and broncho- pulmonary dysplasia (BPD) [10]. However, the effects of hUCB-MSCs on cartilage repair have not been fully evaluated.…”

Stem Cell Therapy for Chronic Myocardial Infarction

“…Traditionally considered an energy-storing organ, adipose tissue is now regarded as an important source of stem cells for the treatment of cardiovascular diseases [72,78] mainly given their capacity to give rise to endothelial [50], smooth muscle [12], and even cardiac cells [4,66]. In an interesting approach, Miyahara et al [51] employed the cell sheet technology to demonstrate that adipose-derived mesenchymal stem cells (AD-MSC) transplanted 4 weeks after coronary artery ligation induced a positive and significant influence on cardiac function 1 month after cell sheet transplantation.…”

Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium

“…Studies on the use of allogenic mesenchymal stem cells (MSCs) for therapeutic angiogenesis have revealed a significant recovery in cardiac function that can be attributed to the unique abilities of MSCs to act as immunomodulators [10,11], integrate into the host myocardium to form new cardiac tissue [12], secrete paracrine effectors, and differentiate into cardiomyocyte-like-cells (CLCs) [13]. MSC-based cellular cardiomyoplasty for IHDs is already in phase II/III clinical trials [8,9,[14][15][16][17].…”