TY - JOUR
T1 - Multilayered adipose-derived regenerative cell sheets created by a novel magnetite tissue engineering method for myocardial infarction
AU - Ishii, Masakazu
AU - Shibata, Rei
AU - Shimizu, Yuuki
AU - Yamamoto, Takashi
AU - Kondo, Kazuhisa
AU - Inoue, Yoko
AU - Ouchi, Noriyuki
AU - Tanigawa, Tohru
AU - Kanemura, Noriyoshi
AU - Ito, Akira
AU - Honda, Hiroyuki
AU - Murohara, Toyoaki
N1 - Funding Information:
This study was supported by a grant (No. 26-J-Jd08 ) from the Japan Science and Technology Agency and a grant (No. 20249045 to T.M.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan . R. Shibata was supported by a Grant-in-Aid for Young Scientists B, Banyu Life Science Foundation International , Kanae Foundation and Kowa Life Science Foundation .
PY - 2014/8/20
Y1 - 2014/8/20
N2 - Background Adipose-derived regenerative cells (ADRCs) are a promising source of autologous stem cells for regeneration and repair of damaged tissue. Herein, we investigated the therapeutic potential of ADRC sheets created by a magnetite tissue engineering technology (Mag-TE) for myocardial infarction. Methods and results Adipose tissue was obtained from wild-type (WT) mice and ADRCs were isolated. ADRCs incubated with magnetic nanoparticle-containing liposomes (MCLs) were cultured. MCL-labeled ADRCs were mixed with a diluted extracellular matrix (ECM) precursor, and a magnet was placed on the reverse side. Magnetized ADRCs formed multilayered cell sheets after a 24-h incubation. WT mice were subjected to myocardial infarction by permanent ligation of the left anterior descending artery. We then transplanted the constructed ADRC sheet or a cell-free collagen gel sheet, as a control, onto the infarcted myocardium using an Alnico magnet before skin closure. Cardiac parameters were measured by echocardiogram, and angiogenesis was determined by tissue capillary density. ADRC sheet-treated mice showed significant improvements in systolic function, infarct wall thinning, and fibrotic length after myocardial infarction. ADRC sheet implantation also promoted angiogenesis in both the infarct area and the border zone in WT mice after myocardial infarction. The angiogenic effects of ADRC sheets were attributed to an increased expression of VEGF and bFGF mRNA in ischemic hearts. Conclusions ADRC sheets created by this Mag-TE method protect the heart against pathological cardiac remodeling. Our ADRC sheets have the potential to be a novel regenerative strategy for ischemic heart disease.
AB - Background Adipose-derived regenerative cells (ADRCs) are a promising source of autologous stem cells for regeneration and repair of damaged tissue. Herein, we investigated the therapeutic potential of ADRC sheets created by a magnetite tissue engineering technology (Mag-TE) for myocardial infarction. Methods and results Adipose tissue was obtained from wild-type (WT) mice and ADRCs were isolated. ADRCs incubated with magnetic nanoparticle-containing liposomes (MCLs) were cultured. MCL-labeled ADRCs were mixed with a diluted extracellular matrix (ECM) precursor, and a magnet was placed on the reverse side. Magnetized ADRCs formed multilayered cell sheets after a 24-h incubation. WT mice were subjected to myocardial infarction by permanent ligation of the left anterior descending artery. We then transplanted the constructed ADRC sheet or a cell-free collagen gel sheet, as a control, onto the infarcted myocardium using an Alnico magnet before skin closure. Cardiac parameters were measured by echocardiogram, and angiogenesis was determined by tissue capillary density. ADRC sheet-treated mice showed significant improvements in systolic function, infarct wall thinning, and fibrotic length after myocardial infarction. ADRC sheet implantation also promoted angiogenesis in both the infarct area and the border zone in WT mice after myocardial infarction. The angiogenic effects of ADRC sheets were attributed to an increased expression of VEGF and bFGF mRNA in ischemic hearts. Conclusions ADRC sheets created by this Mag-TE method protect the heart against pathological cardiac remodeling. Our ADRC sheets have the potential to be a novel regenerative strategy for ischemic heart disease.
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U2 - 10.1016/j.ijcard.2014.06.034
DO - 10.1016/j.ijcard.2014.06.034
M3 - Article
C2 - 25023793
AN - SCOPUS:84905112199
VL - 175
SP - 545
EP - 553
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 3
ER -