Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innat...Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13)[1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1].展开更多
BACKGROUND Heart disease remains a leading cause of mortality worldwide,with existing treatments often failing to effectively restore damaged myocardium.Humaninduced pluripotent stem cells(hiPSCs)and their derivatives...BACKGROUND Heart disease remains a leading cause of mortality worldwide,with existing treatments often failing to effectively restore damaged myocardium.Humaninduced pluripotent stem cells(hiPSCs)and their derivatives offer promising therapeutic options;however,challenges such as low retention,engraftment issues,and tumorigenic risks hinder their clinical utility.Recent focus has shifted to exosomes(exos)-nanoscale vesicles that facilitate intercellular communication-as a safer and more versatile alternative.Understanding the specific mechanisms and comparative efficacy of exos from hiPSCs vs hiPSC-derived cardiomyocytes(hiPSC-CMs)is crucial for advancing cardiac repair therapies.AIM To evaluate and compare the therapeutic efficacy of exos secreted by hiPSCs and hiPSC-CMs in cardiac repair,and to elucidate the role of microRNA 21-5p(miR-21-5p)in the observed effects.METHODS We differentiated hiPSCs into CMs using small molecule methods and characterized the cells and their exos.RESULTS Our findings indicate that hiPSC-CMs and their exos enhanced cardiac function,reduced infarct size,and decreased myocardial fibrosis in a murine myocardial infarction model.Notably,hiPSC-CM exos outperformed hiPSC-CM cell therapy,showing improved ejection fraction and reduced apoptosis.We identified miR-21-5p,a microRNA in hiPSC-CM exos,as crucial for CM survival.Exos with miR-21-5p were absorbed by AC16 cells,suggesting a mechanism for their cytoprotective effects.CONCLUSION Overall,hiPSC-CM exos could serve as a potent therapeutic agent for myocardial repair,laying the groundwork for future research into exos as a treatment for ischemic heart disease.展开更多
基金supported by grants from the National Natural Science Foundation of China (81870874, 31371179, and 81300968)the Natural Science Foundation of Jiangsu Province, China (BK20170004 and 2015-JY-029)
文摘Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13)[1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1].
基金Supported by the Nonprofit Research Institutes Foundation of Fujian Province,China,No.2021R1012005 and No.2021R1012003.
文摘BACKGROUND Heart disease remains a leading cause of mortality worldwide,with existing treatments often failing to effectively restore damaged myocardium.Humaninduced pluripotent stem cells(hiPSCs)and their derivatives offer promising therapeutic options;however,challenges such as low retention,engraftment issues,and tumorigenic risks hinder their clinical utility.Recent focus has shifted to exosomes(exos)-nanoscale vesicles that facilitate intercellular communication-as a safer and more versatile alternative.Understanding the specific mechanisms and comparative efficacy of exos from hiPSCs vs hiPSC-derived cardiomyocytes(hiPSC-CMs)is crucial for advancing cardiac repair therapies.AIM To evaluate and compare the therapeutic efficacy of exos secreted by hiPSCs and hiPSC-CMs in cardiac repair,and to elucidate the role of microRNA 21-5p(miR-21-5p)in the observed effects.METHODS We differentiated hiPSCs into CMs using small molecule methods and characterized the cells and their exos.RESULTS Our findings indicate that hiPSC-CMs and their exos enhanced cardiac function,reduced infarct size,and decreased myocardial fibrosis in a murine myocardial infarction model.Notably,hiPSC-CM exos outperformed hiPSC-CM cell therapy,showing improved ejection fraction and reduced apoptosis.We identified miR-21-5p,a microRNA in hiPSC-CM exos,as crucial for CM survival.Exos with miR-21-5p were absorbed by AC16 cells,suggesting a mechanism for their cytoprotective effects.CONCLUSION Overall,hiPSC-CM exos could serve as a potent therapeutic agent for myocardial repair,laying the groundwork for future research into exos as a treatment for ischemic heart disease.
