論文 - 詳細
| RRC ID | 63579 |
|---|---|
| 著者 | Samura T, Miyagawa S, Kawamura T, Fukushima S, Yokoyama JY, Takeda M, Harada A, Ohashi F, Sato-Nishiuchi R, Toyofuku T, Toda K, Sekiguchi K, Sawa Y. |
| タイトル | Laminin-221 Enhances Therapeutic Effects of Human-Induced Pluripotent Stem Cell-Derived 3-Dimensional Engineered Cardiac Tissue Transplantation in a Rat Ischemic Cardiomyopathy Model. |
| ジャーナル | J Am Heart Assoc |
| Abstract |
Background Extracellular matrix, especially laminin-221, may play crucial roles in viability and survival of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) after in vivo transplant. Then, we hypothesized laminin-221 may have an adjuvant effect on therapeutic efficacy by enhancing cell viability and survival after transplantation of 3-dimensional engineered cardiac tissue (ECT) to a rat model of myocardial infarction. Methods and Results In vitro study indicates the impacts of laminin-221 on hiPS-CMs were analyzed on the basis of mechanical function, mitochondrial function, and tolerance to hypoxia. We constructed 3-dimensional ECT containing hiPS-CMs and fibrin gel conjugated with laminin-221. Heart function and in vivo behavior were assessed after engraftment of 3-dimensional ECT (laminin-conjugated ECT, n=10; ECT, n=10; control, n=10) in a rat model of myocardial infarction. In vitro assessment indicated that laminin-221 improves systolic velocity, diastolic velocity, and maximum capacity of oxidative metabolism of hiPS-CMs. Cell viability and lactate dehydrogenase production revealed that laminin-221 improved tolerance to hypoxia. Furthermore, analysis of mRNA expression revealed that antiapoptotic genes were upregulated in the laminin group under hypoxic conditions. Left ventricular ejection fraction of the laminin-conjugated ECT group was significantly better than that of other groups 4 weeks after transplantation. Laminin-conjugated ECT transplantation was associated with significant improvements in expression levels of rat vascular endothelial growth factor. In early assessments, cell survival was also improved in laminin-conjugated ECTs compared with ECT transplantation without laminin-221. Conclusions In vitro laminin-221 enhanced mechanical and metabolic function of hiPS-CMs and improved the therapeutic impact of 3-dimensional ECT in a rat ischemic cardiomyopathy model. These findings suggest that adjuvant laminin-221 may provide a clinical benefit to hiPS-CM constructs. |
| 巻・号 | 9(16) |
| ページ | e015841 |
| 公開日 | 2020-8-18 |
| DOI | 10.1161/JAHA.119.015841 |
| PMID | 32783519 |
| PMC | PMC7660810 |
| MeSH | Animals Apoptosis / genetics Cell Hypoxia / drug effects Cell Survival* Disease Models, Animal Gene Expression Regulation Heart Transplantation Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / physiology L-Lactate Dehydrogenase / biosynthesis Laminin / pharmacology* Male Myocardial Contraction / physiology Myocardial Infarction / therapy* Myocytes, Cardiac / drug effects* Myocytes, Cardiac / physiology Myocytes, Cardiac / transplantation Neovascularization, Physiologic RNA, Messenger / metabolism Rats Rats, Nude Recombinant Proteins / pharmacology Stroke Volume Tissue Engineering* / methods Up-Regulation Vascular Endothelial Growth Factor A / metabolism Ventricular Remodeling |
| IF | 4.605 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 253G1(HPS0002) |