title: Bioengineered myocardium derived from induced pluripotent stem cells improves cardiac function and attenuates cardiac remodeling following chronic myocardial infarction in rats.
abstract: Cell-based therapies are promising strategies for myocardial repair following myocardial infarction. Induced pluripotent stem (iPS) cells have the potential to generate many cardiomyocytes, and they hold significant promise for the application of regenerative medicine to heart failure. Here, we developed cardiac tissue sheets, termed bioengineered myocardium (BM), from mouse iPS cells and measured cardiac performance following BM implantation in a rat chronic myocardial infarction model. Immunostaining analyses revealed that the α-actinin(+) cell population was isolated with more than 99% purity under specific culture conditions. To evaluate the contribution of BM to the improvements in cardiac performance, we induced myocardial infarction in 30 F344/NJcl-rnu/rnu rats by left anterior descending coronary ligation. The rats were randomly divided into two groups, 2 weeks after ligation: a BM implantation group (n = 15) and a sham group (n = 15). Echocardiography and catheter examination showed that the BM implantation significantly improved cardiac function and attenuated cardiac remodeling compared with the sham group. Histological analyses demonstrated that the implanted BM survived at the epicardial implantation site 4 weeks after implantation. The implanted BM survived and attenuated left ventricular remodeling in the rat chronic myocardial infarction model. Thus, BM derived from iPS cells might be a promising new treatment for heart failure.
authors.affiliation: Department of Surgery, Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miki
authors.forename: Hisazumi
authors.initials: H
authors.lastname: Uenaka
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004452:Echocardiography; D005260:Female; D005355:Fibrosis / Q000517:prevention & control; D006321:Heart / Q000502:physiology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D044968:Regenerative Medicine; D023822:Tissue Engineering; D020257:Ventricular Remodeling