Cardiomyogenic differentiation of human sternal bone marrow mesenchymal stem cells using a combination of basic fibroblast growth factor and hydrocortisone.
The alarming rate of increase in myocardial infarction and marginal success in efforts to regenerate the damaged myocardium through conventional treatments creates an exceptional avenue for cell-based therapy. Adult bone marrow mesenchymal stem cells (MSCs) can be differentiated into cardiomyocytes, by treatment with 5-azacytidine, thus, have been anticipated as a therapeutic tool for myocardial infarction treatment. In this study, we investigated the ability of basic fibroblastic growth factor (bFGF) and hydrocortisone as a combined treatment to stimulate the differentiation of MSCs into cardiomyocytes. MSCs were isolated from sternal marrow of patients undergoing heart surgery (CABG). The isolated cells were initially monitored for the growth pattern, followed by characterization using ISCT recommendations. Cells were then differentiated using a combination of bFGF and hydrocortisone and evaluated for the expression of characteristic cardiac markers such as CTnI, CTnC, and Cnx43 at protein level using immunocytochemistry and flow cytometry, and CTnC and CTnT at mRNA level. The expression levels and pattern of the cardiac markers upon analysis with ICC and qRT-PCR were similar to that of 5-azacytidine induced cells and cultured primary human cardiomyocytes. However, flow cytometric evaluation revealed that induction with bFGF and hydrocortisone drives MSC differentiation to cardiomyocytes with a marginally higher efficiency. These results indicate that combination treatment of bFGF and hydrocortisone can be used as an alternative induction method for cardiomyogenic differentiation of MSCs for future clinical applications.
Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.
Pezhman
P
Hafez
Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.
Shinsmon
S
Jose
Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.
Shiplu R
SR
Chowdhury
Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.
Min Hwei
MH
Ng
Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.|Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
B H I
BH
Ruszymah
Division of Cardiothoracic Surgery, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Ramzisham
R
Abdul Rahman Mohd
D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D009203:Myocardial Infarction; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D013249:Sternum / Q000166:cytology
D016222:Fibroblast Growth Factor 2; D006854:Hydrocortisone
basic fibroblast growth factor; cardiomyocytes; human mesenchymal stem cells; hydrocortisone