Human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)have been widely used in therapy of ischemic heart disease.However,there are still remaining issues that limit the therapeutic efficacy,such as immu...Human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)have been widely used in therapy of ischemic heart disease.However,there are still remaining issues that limit the therapeutic efficacy,such as immune rejection and low retention of hiPSC-CMs.Human adipose mesenchymal stromal cells(hADSCs)have been reported to be able to regulate the immune response,promote angiogenesis and promote the maturation of hiPSC-CMs.In this study,we co-cultured these two types of cells on fiber scaffold made of biodegradable poly(D,L-lactic-co-glycolic acid)(PLGA)polymer for several days to develop a composited 3D cardiac tissue sheet.As expected,the cells formed 231.00±15.14μm thickness tissue,with improved organization,alignment,ECM condition,contractile ability,and paracrine function compared to culture hiPSC-CMs only on PLGA fiber.Furthermore,the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation.The composited 3D cardiac tissue sheet also increased cardiac function,attenuated ventricular remodeling,decreased fibrosis,and enhanced angiogenesis in rat myocardial infarction model,indicating that this strategy wound be a promising therapeutic option in the clinical scenario.展开更多
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supported by the Japan Society for the Promotion of Science (JSPS)Grant-in-Aid for Scientific Research (B) (22H03157 to L.L.and J.L.)supported by Otsuka Toshimi Scholarship Foundation.
文摘Human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)have been widely used in therapy of ischemic heart disease.However,there are still remaining issues that limit the therapeutic efficacy,such as immune rejection and low retention of hiPSC-CMs.Human adipose mesenchymal stromal cells(hADSCs)have been reported to be able to regulate the immune response,promote angiogenesis and promote the maturation of hiPSC-CMs.In this study,we co-cultured these two types of cells on fiber scaffold made of biodegradable poly(D,L-lactic-co-glycolic acid)(PLGA)polymer for several days to develop a composited 3D cardiac tissue sheet.As expected,the cells formed 231.00±15.14μm thickness tissue,with improved organization,alignment,ECM condition,contractile ability,and paracrine function compared to culture hiPSC-CMs only on PLGA fiber.Furthermore,the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation.The composited 3D cardiac tissue sheet also increased cardiac function,attenuated ventricular remodeling,decreased fibrosis,and enhanced angiogenesis in rat myocardial infarction model,indicating that this strategy wound be a promising therapeutic option in the clinical scenario.
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.
