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

Abstract

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.

Adrenomedullin as a Growth and Cell Fate Regulatory Factor for Adult Neural Stem Cells

“…The major problem is the poor survival rate of implanted cells. Overcoming this problem may improve stem cell therapy [145]. As AM is a factor that improves the survival in most cells, one might think of it as a way to improve ASC-induced cardiac regeneration.…”

Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage

“…ADSCs are considered a suitable autologous cell source. Moreover, ADSCs have been used to treat many diseases such as liver fibrosis [19], nerve defects [20-22], ischemia [23,24], skeletal muscle injury [25], passive chronic immune thrombocytopenia [26], and infarcted myocardium [27] in animals; and systemic sclerosis in human [28,29]. …”

Curcumin-Induced Heme Oxygenase-1 Expression Prevents H2O2-Induced Cell Death in Wild Type and Heme Oxygenase-2 Knockout Adipose-Derived Mesenchymal Stem Cells

“…Induction of HO-1 has been demonstrated to improve MSC therapy in vivo by improving tissue functioning of the damaged organ, whereas inhibition of HO-activity worsened MSC therapy outcome in diverse pathologic conditions, such as ischemia reperfusion injury of the heart, pulmonary arterial hypertension, diabetes, and dermal wound healing [31,33,34,35,36,37,38,39,40]. It has been shown in vitro that HO-1 overexpression increases BM-derived MSC survival against oxidative stress, but the exact mechanism remains unknown [17,34].…”