Spermine Treated-Adipose Tissue-Derived Multi-Lineage Progenitor Cells Improve Left Ventricular Dysfunction in a Swine Model of Chronic Myocardial InfarctionHanayuki Okura1-3, Mitsuko Morita1, Maiko Fujita1, Kyoko Naba1, Nozomi Hasebe-Takada1, Akihiro Ichinose4 and Akifumi Matsuyama1,2*
1Platform of Therapeutics for Rare disease, National Institute of Biomedical Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, ARIC 105, 7-1-3 Doicho, Amagasaki, Hyogo, 660-0083, Japan
- *Corresponding Author:
- Akifumi Matsuyama, M.D, Ph.D
Platform of Therapeutics for Rare disease
National Institute of Biomedical Innovation
National Institutes of Biomedical Innovation
Health and Nutrition, Japan
E-mail: [email protected]
Received date January 19, 2016; Accepted date February 05, 2016; Published date February 12, 2016
Citation: Okura H, Morita M, Fujita M, Naba K, Takada NH, et al. (2016) Spermine Treated-Adipose Tissue-Derived Multi-Lineage Progenitor Cells Improve Left Ventricular Dysfunction in a Swine Model of Chronic Myocardial Infarction. J Stem Cell Res Ther 6:326. doi:10.4172/2157-7633.1000326
Copyright: © 2016 Okura H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: The polyamine spermine enhances differentiation of mouse embryonic stem cells into cardiac lineage. The aim of this study was to determine the effects of spermine on the differentiation of human adipose tissuederived multi-lineage progenitor cells (hADMPCs) into cardiomyocytes both in vitro and in vivo and any subsequent functional effect in a swine model of chronic myocardial infarction.
Methods and results: Spermine increased the expression of cardiac markers nkx2.5, islet-1, α-cardiac actin and cardiac troponin I (to 11.2-, 27.5-, 43.6- and 19.1-fold, relative to baseline, respectively) in hADMPCs. Chronic myocardial infarction model with left ventricular dysfunction was induced by balloon occlusion of the diagonal coronary artery followed by reperfusion, with subsequent similar procedure conducted one week later in the left ascending coronary artery (#6). Four weeks later, the immunosuppressed animals (with CyA 5.0 mg/kg intramuscularly (i.m) body weight/day) were transplanted with spermine-treated hADMPC (1×105 , 3×105 , 1×106 or 3×106 cells/kg body weight) via the coronary artery (#6). Cardiac function was assessed by echocardiography at 0, 4, 8 and 12 weeks post-transplantation. Transplantation of these cells improved cardiac function and the most effective dose was 3x105 cells/kg (ejection fraction; 33.4%, 47.0%, 51.5% and 52.9% at 0, 4, 8 and 12 weeks post-transplantation, respectively). At 12-week post-transplantation, spermine-treated hADMPCs differentiated into human-specific troponin I- and α-cardiac actin-positive cells in vivo.
Conclusion: Spermine induced differentiation of hADMPCs into cardiomyocytes both in vitro and in vivo and cellular cardiomyoplasty improved cardiac function. Cellular cardiomyoplasty using hADMPC could be potentially effective cell-based therapy.