Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction

Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lü, Chao; Ran, Qian; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, SF; Zhang, Jianyi; Liu, Chen; Sun, Ninghui

doi:10.1016/j.biomaterials.2016.07.035

Cited by 100 publications

(94 citation statements)

References 37 publications

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“…Conventional electron microscopy was performed as described previously [26]. Human iPSC-CMs and zebrafish embryos at 96 hpf were fixed with 2.5% glutaraldehyde for 1 h at room temperature, followed with three washes with PBS (15 min each), and post-fixed with 1% osmium tetroxide for 2-3 h. The samples were then dehydrated in a graded series of ethanol concentrations and in propylene oxide for 10 min.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells

Zhu

Ding

et al. 2020

Stem Cell Res Ther

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Background:The efficiency and quality of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial for regenerative medicine, disease modeling, drug screening, and the study of the development events during cardiac specification. However, their applications have been hampered by the differentiation efficiency, poor maturation, and high interline variability. Recent studies have reported that histamine plays important roles in hematopoietic stem cell proliferation and neutrophil maturation. However, its roles in cardiovascular tissue regeneration have not been thoroughly investigated. In the current study, we identified a novel physiological function of the histamine/histamine 1 receptor (H 1 R) signal in regulating the differentiation of hiPSC-CMs and heart development.Methods: Transgenic zebrafish model (cmlc2: mCherry) was treated with histamine and histamine receptor (HR) antagonists. Histological morphology and ultrastructure of zebrafish heart were measured. Histamine-deficient pregnant mice (HDC −/− ) were treated with H 1 R antagonist (pyrilamine) by intragastric administration from E8.5 to E18.5. Cardiac histological morphology and ultrastructure were analyzed in neonatal mice, and cardiac function in adult mice was measured. In vitro, histamine and HR antagonists were administrated in the culture medium during hiPSC-CM differentiation at different stages. The efficiency and maturation of cardiac differentiation were evaluated. Finally, histamine-treated hiPSC-CMs were transplanted into ischemic myocardium to detect the possible therapeutic effect.Results: Administration of H 1 R antagonist during heart development induced cardiac dysplasia in zebrafish. Furthermore, using histidine decarboxylase (HDC) knockout mice, we examined abnormal swelling of myocardial mitochondria and autophagy formation under the condition of endogenous histamine deficiency. Histamine significantly promoted myocardial differentiation from human induced pluripotent stem cells (hiPSCs) with better structure and function via a H 1 R-dependent signal. The activation of histamine/H 1 R signaling pathway augmented hiPSC-derived cardiomyocyte (hiPSC-CM) differentiation through the ERK1/2-STAT3 signaling pathway. In addition, histamine-pre-treated hiPSC-CMs were transplanted into the ischemic hearts of myocardial injured mice and exhibited better survival and myocardial protection. Conclusions: Thus, these findings indicated that histamine/H 1 R and its downstream signals were not only involved in cardiac differentiation but also provided a better survival environment for stem cell transplanted into ischemic myocardium.

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Section: Transmission Electron Microscopymentioning

confidence: 99%

Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells

Zhu

Ding

et al. 2020

Stem Cell Res Ther

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“…The heart samples were fixed, paraffin-embedded and sectioned into 5-µm slices. The histological analysis was performed on Masson's trichrome-stained slides from the closest section plane 27 The following data were measured using Image J software: ventricular wall thickness, septum thickness (mm), scar thickness (mm), LV cavity area (mm 2 ) and whole LV area (mm 2 ). Each measurement was performed three times.…”

Section: Histological Analysis Of the LV Cavity Areas And Scar Areasmentioning

confidence: 99%

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Qi¹,

Lü

Li³

et al. 2017

IJN

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The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic- co -glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function ( P <0.05), attenuate the infarct size ( P <0.05), preserve wall thickness ( P <0.05), promote angiogenesis ( P <0.05) and prevent cardiomyocyte apoptosis ( P <0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.

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“…Wang et al produced functional tissue‐engineered human cardiac patches by seeding human iPSCs‐derived cardiac cells onto decellularized natural heart scaffolds. These patches could be used to improve heart function in rat myocardial infarction model (Wang et al, ). In 2008, Ott et al produced whole decellularized heart scaffold by coronary‐mediated detergents perfusion, which preserved perfusable vascular architecture, competent decellularized valves, and complete chamber geometry.…”

Section: Application Of Construction Strategies In Solid Organ Tissuementioning

confidence: 99%

Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization

Zheng

Sui

et al. 2018

J Tissue Eng Regen Med

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Failure of solid organs, such as the heart, liver, and kidney, remains a major cause of the world's mortality due to critical shortage of donor organs. Tissue engineering, which uses elements including cells, scaffolds, and growth factors to fabricate functional organs in vitro, is a promising strategy to mitigate the scarcity of transplantable organs. Within recent years, different construction strategies that guide the combination of tissue engineering elements have been applied in solid organ tissue engineering and have achieved much progress. Most attractively, construction strategy based on whole-organ decellularization has become a popular and promising approach, because the overall structure of extracellular matrix can be well preserved. However, despite the preservation of whole structure, the current constructs derived from decellularization-based strategy still perform partial functions of solid organs, due to several challenges, including preservation of functional extracellular matrix structure, implementation of functional recellularization, formation of functional vascular network, and realization of long-term functional integration. This review overviews the status quo of solid organ tissue engineering, including both advances and challenges. We have also put forward a few techniques with potential to solve the challenges, mainly focusing on decellularization-based construction strategy. We propose that the primary concept for constructing tissue-engineered solid organs is fabricating functional organs based on intact structure via simulating the natural development and regeneration processes.

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Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction

Cited by 100 publications

References 37 publications

Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells

Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization

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