Impact of myocardial infarct proteins and oscillating pressure on the differentiation of mesenchymal stem cells: effect of acute myocardial infarction on stem cell differentiation
| Autor: | Choon Soo Lee, Eun Ju Lee, Yoon Sun Yang, Hyo-Soo Kim, Seock Won Youn, Won-Kyung Ho, Jong Woo Sohn, Hyun-Jai Cho, Shu-Ying Zhang, Lian Li, Hyun Jae Kang, Sung-Eun Yang, Kyung-Woo Park, Young-Bae Park, Ji Hyun Kim, Won Il Oh, Joo-Yun Won, Sung-A Chang, Keum-Hyun Kim |
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| Rok vydání: | 2008 |
| Předmět: |
Umbilical Veins
Cellular differentiation Myocardial Infarction Bone Morphogenetic Protein 2 Biology Bone morphogenetic protein Bone morphogenetic protein 2 Transforming Growth Factor beta1 In vivo Transforming Growth Factor beta Oscillometry Animals Humans Myocytes Cardiac cardiovascular diseases Stem Cells Mesenchymal stem cell Gap Junctions Cell Differentiation Mesenchymal Stem Cells Cell Biology Transforming growth factor beta Rats Transplantation Phenotype Immunology Bone Morphogenetic Proteins Cancer research biology.protein Molecular Medicine Calcium Stem cell Developmental Biology |
| Zdroj: | Stem cells (Dayton, Ohio). 26(7) |
| ISSN: | 1549-4918 |
| Popis: | 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 cardiac-specific 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 β1 (TGF-β1) or bone morphogenetic protein-2 (BMP-2). In vitro cellular and electrophysiologic experiments showed that these differentiated MSCs expressing cardiomyocyte-specific 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-β1 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 infarct-related biological and physical factors in AMI induce commitment of MSCs to cardiomyocyte-like cells through TGF-β/BMP-2 pathways. Disclosure of potential conflicts of interest is found at the end of this article. |
| Databáze: | OpenAIRE |
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