| 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
|
| リソース情報 |
| ヒト・動物細胞 |
253G1(HPS0002) |
