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J Thorac Cardiovasc Surg 2009;138:985-993
© 2009 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

Layered implantation of myoblast sheets attenuates adverse cardiac remodeling of the infarcted heart

Naosumi Sekiya, MDa, Goro Matsumiya, MD, PhDa, Shigeru Miyagawa, MD, PhDa, Atsuhiro Saito, PhDa, Tatsuya Shimizu, MD, PhDb, Teruo Okano, PhDb, Naomasa Kawaguchi, PhDc, Nariaki Matsuura, MD, PhDc, Yoshiki Sawa, MD, PhDa,*

a Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
b Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan
c Department of Molecular Pathology, Osaka University Graduate School of Allied Health Science, Osaka, Japan

Received for publication May 15, 2008; revisions received January 7, 2009; accepted for publication February 2, 2009.

* Address for reprints: Yoshiki Sawa, MD, PhD, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan. (Email: sawa{at}surg1.med.osaka-u.ac.jp).

Objective: We previously showed that autologous myoblast sheets constructed with tissue-engineering techniques improved the function of the impaired heart. In this study, we evaluated the effects of layered myoblast sheets to clarify whether increasing the number of sheets provides improvement of cardiac function.

Methods: Myoblast sheets were constructed in dishes that release confluent cells from the dish surface via temperature reduction. Sixty infarcted Lewis rats underwent implantation of myoblast sheets on the infarcted area. There were 4 groups (n = 15 in each group): S1: one layer, S3: three layers, S5: five layers, and a sham group. We examined cardiac function by echocardiography and catheterization, mRNA expression by real time reverse-transcriptase polymerase chain reaction, and histology.

Results: The ejection fraction and end-systolic pressure–volume relationship in the S5 and S3 groups were significantly improved. End-diastolic area was significantly reduced in the S5 group. The mRNAs for hepatocyte growth factor, vascular endothelial growth factor, and stromal cell–derived factor-1 were all up-regulated in dose-dependent fashion. On histologic examination, fibrosis was most decreased in S5, and vascular density was increased. Cellular hypertrophy was attenuated in both the S5 and S3 groups. Elastic fibers were massively up-regulated in the infarction and implanted sheets in the S5 and S3 groups, with expression of the elastin gene.

Conclusions: Implantation of three- and five-layered myoblast sheets yields favorable results, with better improvement of cardiac function, induction of angiogenesis, more elastic fibers, and less fibrosis. Thus, layered myoblast sheets, in optimal numbers, may attenuate adverse cardiac remodeling of the infarcted heart.

Abbreviations and Acronyms HGF = hepatocyte growth factor; LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction; RT-PCR = reverse-transcription polymerase chain reaction; SDF-1 = stromal-derived factor 1; VEGF = vascular endothelial growth factor






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