Abstract
Background - Mesenchymal stem cells (MSCs) offer a novel therapeutic option in the treatment of acute myocardial infarction. MSCs are able to differentiate into myogenic cells after 5-azacytitdine treatment. However, 5-azacytidine might have genotoxic effects. Recently, it was reported that combined treatment with bone morphogenetic protein-2(BMP-2) and fibroblast growth factor-4(FGF-4) caused cardiac differentiation in non-precardiac mesoderm explants. Therefore, we investigated whether MSCs treated with combined BMP-2 and FGF-4 showed evidence of myogenic differentiation in vitro, and whether these cells resulted in sustained engraftment, myogenic differentiation, and improved cardiac function after implantation in infarcted myocardium. Methods and results - In vitro study: MSCs were treated with BMP-2 + FGF-4 (GF-MSCs) and myogenic phenotype was evaluated immunohistochemically. Cell growth curve was used to compare MSC proliferative capacity between the growth factors and 5-azacytidine treatments. In vivo study: two weeks after coronary artery occlusion, GF-MSCs (n = 15), MSCs (n = 5) labelled with PKH26 were injected into infarcted myocardium. Control animals (n = 5) received a culture medium into the infarcted myocardium. Two weeks after implantation, some engrafted GF-MSCs or MSCs expressed sarcomeric-α-actinin and cardiac myosin heavy chain, as was observed in culture. Echocardiography showed that the GF-MSC group had a better (p < 0.05) left ventricular performance than the other groups. Conclusion - GF-MSCs induced myogenic differentiation in vitro. Moreover, GF-MSCs engrafted into the infarcted myocardium increased myogenic differentiation, prevented dilation of the infarcted region, and eventually improved heart function.
| Original language | English |
|---|---|
| Pages (from-to) | 277-284 |
| Number of pages | 8 |
| Journal | Acta Cardiologica |
| Volume | 60 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2005 Jun 1 |
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Keywords
- BMP-2/FGF-4
- Myocardial infarction
- Transplantation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. / Yoon, Jihyun; Min, Byoung Goo; Kim, Young Hoon; Shim, Wan Joo; Ro, Young Moo; Lim, Do-Sun.
In: Acta Cardiologica, Vol. 60, No. 3, 01.06.2005, p. 277-284.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model
AU - Yoon, Jihyun
AU - Min, Byoung Goo
AU - Kim, Young Hoon
AU - Shim, Wan Joo
AU - Ro, Young Moo
AU - Lim, Do-Sun
PY - 2005/6/1
Y1 - 2005/6/1
N2 - Background - Mesenchymal stem cells (MSCs) offer a novel therapeutic option in the treatment of acute myocardial infarction. MSCs are able to differentiate into myogenic cells after 5-azacytitdine treatment. However, 5-azacytidine might have genotoxic effects. Recently, it was reported that combined treatment with bone morphogenetic protein-2(BMP-2) and fibroblast growth factor-4(FGF-4) caused cardiac differentiation in non-precardiac mesoderm explants. Therefore, we investigated whether MSCs treated with combined BMP-2 and FGF-4 showed evidence of myogenic differentiation in vitro, and whether these cells resulted in sustained engraftment, myogenic differentiation, and improved cardiac function after implantation in infarcted myocardium. Methods and results - In vitro study: MSCs were treated with BMP-2 + FGF-4 (GF-MSCs) and myogenic phenotype was evaluated immunohistochemically. Cell growth curve was used to compare MSC proliferative capacity between the growth factors and 5-azacytidine treatments. In vivo study: two weeks after coronary artery occlusion, GF-MSCs (n = 15), MSCs (n = 5) labelled with PKH26 were injected into infarcted myocardium. Control animals (n = 5) received a culture medium into the infarcted myocardium. Two weeks after implantation, some engrafted GF-MSCs or MSCs expressed sarcomeric-α-actinin and cardiac myosin heavy chain, as was observed in culture. Echocardiography showed that the GF-MSC group had a better (p < 0.05) left ventricular performance than the other groups. Conclusion - GF-MSCs induced myogenic differentiation in vitro. Moreover, GF-MSCs engrafted into the infarcted myocardium increased myogenic differentiation, prevented dilation of the infarcted region, and eventually improved heart function.
AB - Background - Mesenchymal stem cells (MSCs) offer a novel therapeutic option in the treatment of acute myocardial infarction. MSCs are able to differentiate into myogenic cells after 5-azacytitdine treatment. However, 5-azacytidine might have genotoxic effects. Recently, it was reported that combined treatment with bone morphogenetic protein-2(BMP-2) and fibroblast growth factor-4(FGF-4) caused cardiac differentiation in non-precardiac mesoderm explants. Therefore, we investigated whether MSCs treated with combined BMP-2 and FGF-4 showed evidence of myogenic differentiation in vitro, and whether these cells resulted in sustained engraftment, myogenic differentiation, and improved cardiac function after implantation in infarcted myocardium. Methods and results - In vitro study: MSCs were treated with BMP-2 + FGF-4 (GF-MSCs) and myogenic phenotype was evaluated immunohistochemically. Cell growth curve was used to compare MSC proliferative capacity between the growth factors and 5-azacytidine treatments. In vivo study: two weeks after coronary artery occlusion, GF-MSCs (n = 15), MSCs (n = 5) labelled with PKH26 were injected into infarcted myocardium. Control animals (n = 5) received a culture medium into the infarcted myocardium. Two weeks after implantation, some engrafted GF-MSCs or MSCs expressed sarcomeric-α-actinin and cardiac myosin heavy chain, as was observed in culture. Echocardiography showed that the GF-MSC group had a better (p < 0.05) left ventricular performance than the other groups. Conclusion - GF-MSCs induced myogenic differentiation in vitro. Moreover, GF-MSCs engrafted into the infarcted myocardium increased myogenic differentiation, prevented dilation of the infarcted region, and eventually improved heart function.
KW - BMP-2/FGF-4
KW - Myocardial infarction
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=20444465738&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20444465738&partnerID=8YFLogxK
U2 - 10.2143/AC.60.3.2005005
DO - 10.2143/AC.60.3.2005005
M3 - Article
C2 - 15999467
AN - SCOPUS:20444465738
VL - 60
SP - 277
EP - 284
JO - Acta Cardiologica
JF - Acta Cardiologica
SN - 0001-5385
IS - 3
ER -