Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model

Jihyun Yoon, Byoung Goo Min, Young Hoon Kim, Wan Joo Shim, Young Moo Ro, Do-Sun Lim

Research output: Contribution to journalArticle

73 Citations (Scopus)

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 languageEnglish
Pages (from-to)277-284
Number of pages8
JournalActa Cardiologica
Volume60
Issue number3
DOIs
Publication statusPublished - 2005 Jun 1

Fingerprint

Mesenchymal Stromal Cells
Myocardial Infarction
Fibroblast Growth Factor 4
Bone Morphogenetic Protein 2
Myocardium
Azacitidine
Cardiac Myosins
Actinin
Myosin Heavy Chains
Coronary Occlusion
Mesoderm
Culture Media
Echocardiography
Dilatation
Intercellular Signaling Peptides and Proteins
Coronary Vessels
Phenotype

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 journalArticle

Yoon, Jihyun ; Min, Byoung Goo ; Kim, Young Hoon ; Shim, Wan Joo ; Ro, Young Moo ; Lim, Do-Sun. / Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. In: Acta Cardiologica. 2005 ; Vol. 60, No. 3. pp. 277-284.
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