Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes.
BACKGROUND
Mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes if an appropriate cellular environment is provided. Notch signals exchanged between neighboring cells through the Notch receptor can eventually dictate cell differentiation. In our study, we show that MSC differentiation into cardiomyocytes is dependent on the Notch signal.


METHODS
We created a myocardial infarction model in rat by coronary ligation, administered direct intramyocardial injection of DAPI-labeled MSC immediately, and observed the differentiation of MSCs after 14 days by immunofluorescence staining against troponin T. We cultured MSCs and cardiomyocytes in four ways, respectively, in vitro. (1) MSCs cocultured with cardiomyocytes obtained from neonatal rat ventricles in a ratio of 1:10. (2) The two types of cells were cultured in two chambers separated by a semipermeable membrane as indirect coculture group. (3) Notch receptor-soluble jagged1 protein was added to indirect coculture group. (4) Both jagged1 protein and gamma-secretase inhibitor-DAPT were added to indirect coculture group. Two weeks later, we observed the differentiation percentage, respectively, by immunofluorescence staining.


RESULTS
We found the differentiation of MSCs which were close to cardiomyocytes in vivo. The differentiation percentage of the four cell culture group was 30.13+/-2.16%, 12.52+/-1.18%, 26.33+/-2.20%, and 13.08+/-1.15%.


CONCLUSIONS
MSCs can differentiate into cardiomyocytes in vitro and in vivo if a cardiomyocyte microenvironment is provided. 2. Cell-to-cell interaction is very important for the differentiation of MSCs into cardiomyocytes. 3. Jagged1 protein can activate Notch signal and enhance the differentiation of MSC into cardiomyocyte, while the effect can be inhibited by DAPT.
Li
Houwei
H
Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China. lihouwei-zy@163.com
Yu
Bo
B
Zhang
Yan
Y
Pan
Zhenwei
Z
Xu
Wei
W
Li
Hulun
H
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004562:Electrocardiography; D005109:Extracellular Matrix / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D015233:Models, Statistical; D009203:Myocardial Infarction / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors
D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins