Abstract 20417: Muscle Derived New Cell Population Has Therapeutic Potentials Through Paracrine Effects in Cell-sheet Transplantation in a Rat Ischemic Cardiomyopathy Model
Background: Transplantation of autologous skeletal myoblast (SMB) cell-sheets has been shown to produce therapeutic effects via paracrine effects in ischemic cardiomyopathy (ICM). Although purity of the SMB is considered to be related to functionality of the cell-sheets and the consequent therapeutic effects, little is known about therapeutic role of non-myogenic cell (NMC) population in the SMB cell-sheets, which include fibroblasts or vascular cells. We hypothesized that NMC population may contribute to paracrine effects of the SMB cell-sheet transplantation on ICM in a different manner from pure SMB population.
Methods: Primary SMB of human origin were isolated by enzymatic digestion of the vastus medialis muscle, expanded and sorted by SMB-specific marker, CD56, by fluorescence-activated cell sorting. Therapeutic potentials of the SMBs, CD56(-) NMCs , and mixture of them (Mix) were assessed in vitro and in vivo.
Results: NMCs expressed fibroblast marker, TE-7, endothelial marker, CD201, but rarely expressed CD31. SMBs under cultivation predominantly expressed GCSF, while NMCs predominantly expressed HGF and SDF as assessed by immunoassays. VEGF was expressed to the same degree among the three groups. In addition, every cell-preparation promoted tube formation of human umbilical vein endothelial cells and transwell migration of mesenchymal stem cells, though the degree of the effects was the greatest in the NMCs. Subsequently, a nude rat ICM model was generated by coronary artery ligation for 2 weeks, followed by transplantation of SMB, NMC, or Mix cell-sheets, or sham operation (n=12 each). Ejection fraction was significantly improved in the cell-sheet transplanted rats without significant difference in the degree of improvement among the groups (SMB; 50±4%, NMC; 52±6% and Mix; 53±4%), as compared to the control (45±5%; P <0.05). Capillary density in the peri-infarct myocardium was significantly greater in the NMCs and the Mix than the control, whereas collagen accumulation was significantly smaller in all cell groups than the control.
Conclusions: The NMCs have therapeutic potentials through different paracrine effects in a rat ICM model from pure SMBs, warranting further studies to optimize cell culture protocols of SMBs in treating ICM.
Author Disclosures: H. Iseoka: None. S. Miyagawa: None. S. Fukushima: None. A. Saito: None. S. Masuda: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.