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Developing Thick Cardiac Tissue with a Multilayer Fiber Sheet for Treating Myocardial Infarction

Advanced Fiber Materials 2023年第6期5卷 1905-1918页

作者： Junjun Li Xiang Qu Li Liu Lingjun Li Ying Hua Jingbo Zhang Masako Ishida Noriko Yoshida akiko tabata Nagako Sougawa Emiko Ito Noriko Mochizuki‑Oda Akima Harada Takuji Kawamura Ryohei Matsuura Yingzhe Wang Keisuke Morishima Shigeru Miyagawa Yoshiki Sawa Department of Cardiovascular Surgery Osaka University Graduate School of Medicine2‑2 YamadaokaSuita 565‑0871Japan Frontier of regenerative medicine Osaka University Graduate School of Medicine2‑2 YamadaokaSuita 565‑0871Japan Department of Physiology Osaka Dental University8‑1 Kuzuha Hanazono‑choHirakata 573‑1121Japan Department of Mechanical Engineering Graduate School of EngineeringOsaka UniversitySuita 565‑0871Japan Global Center for Medical Engineering and Informatics Osaka UniversityOsaka 565‑0071Japan Division of Health Sciences Osaka University Graduate School of MedicineSuita 565‑0871Japan

Human-induced pluripotent stem cell (hiPSC)-derived cardiac patches have been extensively used for treating myocardialinfarction and have shown potential for clinical application. However, the limited patch thickness can hamper its therapeuticeffect. We previously developed a fibrous scaffold that allowed the formation of well-organized cardiac tissue constructs. Inthe present study, based on the above technology, we developed a three-dimensional multilayer fibrous scaffold with dynamicperfusion, on which approximately 20 million hiPSC-derived cardiomyocytes (CMs) could be seeded in a single step andorganized into 1 mm thick and viable tissue. The multilayer cardiac tissue demonstrated enhanced contractile properties andupregulated cytokine secretion compared with the control group. Notably, when used on the myocardial infarction model,the multilayer group showed improved functional recovery and less fibrosis. These results indicated that the appropriatehiPSC-CM dose requires careful evaluation in developing clinical therapy. The multilayer cardiac tissue group demonstratedsignificant improvement than the control group, indicating that higher doses of transplanted cells may have improvedtherapeutic effects in treating myocardial infarction.

关键词： Fiber Tissue engineering Pluripotent stem cell Cardiomyocyte Myocardial infarction Regenerative therapy

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