Tohoku J. Exp. Med., 2012, 226(3)

Transplantation of Adipose Tissue-Derived Stem Cells Overexpressing Heme Oxygenase-1 Improves Functions and Remodeling of Infarcted Myocardium in Rabbits

JUN-JIE YANG,^1,2 XIA YANG,¹ ZHI-QIANG LIU,² SHUN-YIN HU,¹ ZHI-YAN DU,² LAN-LAN FENG,² JIAN-FENG LIU¹ and YUN-DAI CHEN¹

¹Department of Cardiology, PLA General Hospital, Beijing, P.R. China
²Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, P.R. China

Adipose tissue-derived stem cells (ADSCs) are a promising source of autologous stem cells that are used for regeneration and repair of infracted heart. However, the efficiency of their transplantation is under debate. One of the possible reasons for marginal improvement in ADSCs transplantation is the significant cell death rate of implanted cells after being grafted into injured heart. Therefore, overcoming the poor survival rate of implanted cells may improve stem cell therapy. Due to limited improvement concerning direct stem cell therapy, gene-transfer methods are used to enhance cellular cardiomyoplasty efficacy. Heme oxygenase-1 (HO-1) can provide various types of cells with protection against oxidative injury and apoptosis. However, exact effects of autologous ADSCs combined with HO-1 on cardiac performance remains unknown. In this study, rabbits were treated with ADSCs transduced with HO-1 (HO-1-ADSCs), treated with non-transduced ADSCs, or injected with phosphate buffered saline 14 days after experimental myocardial infarction was induced, when autologous ADSCs were obtained simultaneously. Four weeks after injection, echocardiography showed significant improvements for cardiac functions and left ventricular dimensions in HO-1-ADSCs-treated animals. Structural consequences of transplantation were determined by detailed histological analysis, which showed differentiation of HO-1-ADSCs to cardiomyocyte-like tissues and lumen-like structure organizations. Apart from improvement in angiogenesis and scar areas, more connexin 43-positive gap junction and greater tyrosine hydroxylase-positive cardiac sympathetic nerves sprouting were observed in the HO-1-ADSCs-treated group compared with ADSCs group. These data suggest that the transplantation of autologous ADSCs combined with HO-1 transduction is a feasible and efficacious method for improving infarcted myocardium.

keywords —— adipose tissue-derived stem cells; gene transfer; heme oxygenase-1; myocardial infarction; rabbit

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 226, 231-241

Correspondence: Yun-dai Chen, M.D., Ph.D., Department of Cardiology, Chinese PLA General Hospital, 28 Fuxing Rd, Beijing 100853, P.R. China.

e-mail: cyundai301@sina.com