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 ...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.展开更多
基金Osaka University.This research was supportedby the Japan Agency for Medical Research and Development(AMED)under GrantNumber jp22bm0204003hthe Japan Society for the Promotion of Science(JSPS)Grant-in-Aid for Scientific Research(A)under Grant Number 20H00542+1 种基金Grantin-Aidfor Scientific Research(B)under Grant Number(22H03157)X.Qu was supportedby the Ministry of Education,Culture,Sports,Science,and Technology(MEXT)scholarship.
文摘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.
