iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium
Article first published online: 28 JUN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 8, pages 1644–1654, August 2014
How to Cite
Miao, Q., Shim, W., Tee, N., Lim, S. Y., Chung, Y. Y., Ja, K. P. M. M., Ooi, T. H., Tan, G., Kong, G., Wei, H., Lim, C. H., Sin, Y. K. and Wong, P. (2014), iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium. Journal of Cellular and Molecular Medicine, 18: 1644–1654. doi: 10.1111/jcmm.12351
- Issue published online: 2 SEP 2014
- Article first published online: 28 JUN 2014
- Manuscript Accepted: 19 MAY 2014
- Manuscript Received: 19 FEB 2014
- National Research Foundation Singapore. Grant Number: NRF-003-CRP-002
- Goh Foundation. Grant Number: Duke-NUS-GCR/2013/0011
- Biomedical Research Council Singapore. Grant Number: 13/1/96/19/86
- cell therapy;
- myocardial strain;
- tissue deformation;
- myocardial compliance
We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) in infarcted myocardium. Acute myocardial infarction (MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 105 iMSCs or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Global and regional myocardial function was assessed serially at 1-week and 8-week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1-week and persisted to 8-week with global contractility of ejection fraction and fractional area change in saline- (32.96 ± 14.23%; 21.50 ± 10.07%) and iMSC-injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P < 0.05; 34.86 ± 9.82%, P < 0.05). However, myocardial dilatation was observed in saline-injected animals (4.40 ± 0.62 mm, P < 0.05), but not iMSCs (4.29 ± 0.57 mm), when compared to sham control (3.74 ± 0.32 mm). Furthermore, strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P < 0.05) in the iMSC group, but not saline-injected (15.81 ± 13.92%), when compared to sham control (22.18 ± 4.13%). This was corroborated by multi-segments deterioration of radial strain only in saline-injected (21.50 ± 5.31%, P < 0.05), but not iMSC (25.67 ± 12.53%), when compared to sham control (34.88 ± 5.77%). Improvements of the myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of iMSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine-driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium.