Chitosan/silk fibroin modified nanofibrous patches with mesenchymal stem cells prevent heart remodeling post-myocardial infarction in rats

Chen, Jiangwei; Zhan, Yingfei; Wang, Yabin; Han, Dongyi; Tao, Bo; Luo, Zhenli; Ma, Sai; Wang, Qun; Li, Xiang; Fan, Li; Li, Congye; Deng, Hongbing; Cao, Feng

doi:10.1016/j.actbio.2018.09.013

Cited by 189 publications

(74 citation statements)

References 67 publications

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“…After the hemodynamic assessment, the ligature around the coronary artery was fastened, and Evans Blue/TTC doublestaining was performed to evaluate the infarct size as we previously described. 33 Briefly, 60-80 μL of 2% Evans Blue dye was injected into the coronary system via the root of the ascending aorta after clipping the distal end of ascending aorta. The heart was then incised into 1-mm transverse slices, followed by incubation in 1.5% triphenyltetrazolium chloride (TTC) stain (Sigma-Aldrich, St Louis, Mo) at 37°C for 10 minutes.…”

Section: Evans Blue/ttc Double-stainingmentioning

confidence: 99%

Activation of melatonin receptor 2 but not melatonin receptor 1 mediates melatonin‐conferred cardioprotection against myocardial ischemia/reperfusion injury

Han

Wang

Chen

et al. 2019

Journal of Pineal Research

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Accumulated pieces of evidence have proved the beneficial effects of melatonin on myocardial ischemia/reperfusion (MI/R) injury, and these effects were largely dependent on melatonin membrane receptor activation. In humans and other mammals, there are two types of melatonin receptors, including the melatonin receptor 1 (MT1, melatonin receptor 1a or MTNR1A) and melatonin receptor 1 (MT2, melatonin receptor 1b or MTNR1B) receptor subtypes. However, which receptor mediates melatonin‐conferred cardioprotection remains unclear. In this study, we employed both loss‐of‐function and gain‐of‐function approaches to reveal the answer. Mice (wild‐type; MT1 or MT2 silencing by in vivo minicircle vector; and those overexpressing MT1 or MT2 by in vivo AAV9 vector) were exposed to MI/R injury. Both MT1 and MT2 were present in wild‐type myocardium. MT2, but not MT1, was essentially upregulated after MI/R Melatonin administration significantly reduced myocardial injury and improved cardiac function after MI/R Mechanistically, melatonin treatment suppressed MI/R‐initiated myocardial oxidative stress and nitrative stress, alleviated endoplasmic reticulum stress and mitochondrial injury, and inhibited myocardial apoptosis. These beneficial actions of melatonin were absent in MT2‐silenced heart, but not the MT1 subtype. Furthermore, AAV9‐mediated cardiomyocyte‐specific overexpression of MT2, but not MT1, mitigated MI/R injury and improved cardiac dysfunction, which was accompanied by significant amelioration of oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Mechanistically, MT2 protected primary cardiomyocytes against hypoxia/reoxygenation injury via MT2/Notch1/Hes1/RORα signaling. Our study presents the first direct evidence that the MT2 subtype, but not MT1, is a novel endogenous cardiac protective receptor against MI/R injury. Medications specifically targeting MT2 may hold promise in fighting ischemic heart disease.

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Section: Evans Blue/ttc Double-stainingmentioning

confidence: 99%

Activation of melatonin receptor 2 but not melatonin receptor 1 mediates melatonin‐conferred cardioprotection against myocardial ischemia/reperfusion injury

Han

Wang

Chen

et al. 2019

Journal of Pineal Research

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“…The treatments focus on retaining the function of the remaining cardiomyocytes, but myocardial infarction (MI) still remains a major cause of morbidity and mortality worldwide (1,2) . Recently, mesenchymal stem cells (MSCs) transplantation has held great promise for multiple diseases, such as MI (3)(4)(5)(6) . The illustrated underlying therapeutic mechanisms include engraftment (7) , paracrine (8) and other effects, like exosomes (6) .…”

Section: Introductionmentioning

confidence: 99%

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Deng

Zhang

Wang

et al. 2020

Preprint

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Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

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“…Cytokine release enhanced the recruitment of endogenous c-kit+ cells and activated the epicardium [ 103 ]. Chen and colleagues designed a novel chitosan and silk fibroin microfibrous cardiac patch that significantly improved the survival of murine adipose tissue-derived MSCs in infarcted hearts of a rat model [ 104 ]. This was achieved due to the structural resemblance of the patch to the native ECM of the heart.…”

Section: Biomaterials Loaded With Stem Cells For Cardiac Tissue Rementioning

confidence: 99%

Biomaterials Loaded with Growth Factors/Cytokines and Stem Cells for Cardiac Tissue Regeneration

Smagul

Kim

Smagulova

et al. 2020

IJMS

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Myocardial infarction causes cardiac tissue damage and the release of damage-associated molecular patterns leads to activation of the immune system, production of inflammatory mediators, and migration of various cells to the site of infarction. This complex response further aggravates tissue damage by generating oxidative stress, but it eventually heals the infarction site with the formation of fibrotic tissue and left ventricle remodeling. However, the limited self-renewal capability of cardiomyocytes cannot support sufficient cardiac tissue regeneration after extensive myocardial injury, thus, leading to an irreversible decline in heart function. Approaches to improve cardiac tissue regeneration include transplantation of stem cells and delivery of inflammation modulatory and wound healing factors. Nevertheless, the harsh environment at the site of infarction, which consists of, but is not limited to, oxidative stress, hypoxia, and deficiency of nutrients, is detrimental to stem cell survival and the bioactivity of the delivered factors. The use of biomaterials represents a unique and innovative approach for protecting the loaded factors from degradation, decreasing side effects by reducing the used dosage, and increasing the retention and survival rate of the loaded cells. Biomaterials with loaded stem cells and immunomodulating and tissue-regenerating factors can be used to ameliorate inflammation, improve angiogenesis, reduce fibrosis, and generate functional cardiac tissue. In this review, we discuss recent findings in the utilization of biomaterials to enhance cytokine/growth factor and stem cell therapy for cardiac tissue regeneration in small animals with myocardial infarction.

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Chitosan/silk fibroin modified nanofibrous patches with mesenchymal stem cells prevent heart remodeling post-myocardial infarction in rats

Cited by 189 publications

References 67 publications

Activation of melatonin receptor 2 but not melatonin receptor 1 mediates melatonin‐conferred cardioprotection against myocardial ischemia/reperfusion injury

Activation of melatonin receptor 2 but not melatonin receptor 1 mediates melatonin‐conferred cardioprotection against myocardial ischemia/reperfusion injury

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Biomaterials Loaded with Growth Factors/Cytokines and Stem Cells for Cardiac Tissue Regeneration

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