Mesenchymal Stem Cells Express Low Levels of Cardiomyogenic Genes and Show Limited Plasticity towards Cardiomyogenic Phenotype

作     者：Juliana Lott de Carvalho Danilo Roman Campos Maira Souza Oliveira Jader Santos Cruz Nathalia Martins Breyner Dawidson Assis Gomes Alfredo Miranda de Goes 

作者机构：Department of Biochemistry and Immunology Institute of Biological Sciences Federal University of Minas Gerais Belo Horizonte 30123-970 Minas Gerais Brazil Department of Pharmacology Columbia University Presbyterian Hospital New York 10032 United States Department of Clinic and Surgery College of Veterinary Medicine Federal University of Minas Gerais Belo Horizonte 30123-970 Minas Gerais Brazil Institut National de Recherche Agronomique Paris 75338 France 

出 版 物：《Journal of Life Sciences》 (生命科学（英文版）)

年 卷 期：2013年第7卷第9期

页      面：950-964页

学科分类：0710[理学-生物学] 07[理学] 08[工学] 071008[理学-发育生物学] 09[农学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

主　　题：骨髓间充质干细胞 心肌细胞分化 细胞表达 基因表达 可塑性 高水 实时荧光定量PCR 分化培养基 

摘      要：Mesenchymal stem cell differentiation towards osteogenic, chondrogenic and adipogenic lineages have been extensively described and reproduced in the literature. In contrast, cardiomyogenic differentiation still remains largely controversial. In this study, the authors aim to shed new light into this unclear phenomenon and test whether BMMSC (bone marrow mesenchymal stem cells) and ATMSC (adipose tissue derived mesenchymal stem cells) are able to differentiate into functional cardiomyocytes, investigating two differentiation protocols. AT and BMMSC behaved differently when cultured in differentiation media and presented lower levels of proliferation and alkaline phosphatase production, expression of cardiomyocyte-specific transcription factors such as GATA-4, Nkx2-5 and proteins such as α and β Myosin Heavy Chains. Furthermore, MSC started to express higher levels of Connexin-43 and α sarcomeric actinin protein. Unfortunately, though, MSC did not present cardiomyocyte-like electrophysiological properties. In order to analyze a possible explanation for such limited plasticity, the authors decided to address the issue using a quantitative approach. Gene expression was quantified by Real time PCR, and, for the first time, the authors show that a possible explanation for limited plasticity of MSC is that even though differentiated cells presented differential gene expression, the levels of key cardiomyogenic genes did not reach expression levels presented by adult cardiomyocytes, nor were maintained along differentiation, reaching peaks at 4 days of stimulation, and decaying thereafter.