Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy

Kawamura, Masashi; Paulsen, Michael J.; Goldstone, Andrew B.; Shudo, Yasuhiro; Wang, Hanjay; Steele, Amanda N.; Stapleton, Lyndsay M.; Edwards, Bryan B.; Eskandari, Anahita; Truong, Vi N.; Jaatinen, Kevin J; Ingason, Arnar B.; Miyagawa, Shigeru; Sawa, Yoshiki; Woo, Y. Joseph

doi:10.1186/s12933-017-0625-4

Cited by 27 publications

(21 citation statements)

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“…BM-EPCs cells, which have the advantage of a higher proliferation rate and can facilitate vessel formation and produce pro-angiogenic factors to enhance vascularization after implantation, have been regarded as an ideal candidates to address vascular issues alonely or in cocultured with other cells. Recently, Kawamura et al reported that MSCs and BM-EPC cells, as colayered cell sheets, prevented cardiac dysfunction and microvascular disease [12]. Another study showed that EPC-SMC bilevel cell sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating a structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function [29].…”

Section: Discussionmentioning

confidence: 99%

“…SDF-1α/CXCR4 could also decrease EPC cell apoptosis under serum deprivation or hypoxic conditions via the PI3K/AKT/eNOS pathway [10,11]. Some animal studies indicated that BM-EPC cell sheet technology increased vasculogenesis [12]. However, BM-EPCs cell sheet can not harvested with trypsin and cell-to-cell interactions and the integral structure of the BM-EPCs sheet were unknown [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Fabrication and Paracrine Effect Research of Bone Marrow-Derived Endothelial Progenitor Cell Sheet

Xue¹,

Yin²,

Bai³

et al. 2020

Preprint

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Background: The release of a wide array of endothelial progenitor cell (EPC) sheet-secreted paracrine factors is central to the mechanism by which these cells contribute to tissue repair. The purpose of this study was to fabricate BM-EPC sheet and conduct preliminary investigation on the paracrine effect of SDF-1ɑ about the role of the stromal cell-derived factor-1α (SDF-1α)/CXCR4 axis in the form of tubular structures from BM-EPCs sheet.Methods: EPCs derived from rat bone marrow (BM-EPC) were identified and isolated by the cell-surface markers CD34/CD133/VE-cadherin/KDR using flow cytometry, as well as by dual affinity for acLDL and UEA-1. Single-cell suspensions were seeded on temperature-responsive cell culture dishes. After 7 days of incubation, the BM-EPC cells were easily harvested as cell sheets, and a series of biochemical experiments were performed in vitro. The expression levels of SDF-1α/CXCR4 axis-associated genes and proteins were examined using RT‑qPCR and western blot analysis, and enzyme-linked immunosorbent assay (ELISA) was applied to determine the concentrations of VEGF, EGF and SDF-1α in the cell culture medium.Results: The BM-EPC cell sheets were successfully harvested. Moreover, BM-EPC cell sheets have superior proliferation and tube formation activity when compare with single cell suspension. When capillary-like tube were formed from EPCs sheets, the releasing of paracrine factors such as VEGF, EGF, and SDF-1ɑ were increasing. To drive the tube formation of BM-EPCs sheets, our mechanism research showed that the activation of PI3K/AKT/eNOS pathway since the phosphorylation of protein CXCR, PI3K, AKT and eNOS were increasing. Conclusion: BM-EPC cell sheets have superior proliferation and tube formation activity that can be used for tissue repair. The strong ability to secrete paracrine factors was be related to the SDF-1α/CXCR4 axis through PI3K/AKT/eNOS pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fabrication and Paracrine Effect Research of Bone Marrow-Derived Endothelial Progenitor Cell Sheet

Xue¹,

Yin²,

Bai³

et al. 2020

Preprint

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“…For a comprehensive study in DMH it is essential to have a reliable and convenient animal model. STZ, the most widely used chemical to induce diabetes, selectively damages pancreatic cells, causes cell necrosis and results in reduced blood insulin and elevated blood sugar . However, systematic research on the development and examination of cardiac hypertrophy after diabetes onset is scarce.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

Zhang

Qiu

Huang

et al. 2018

Int J Experimental Path

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Summary The aim of this study was to establish a robust model of diabetic myocardial hypertrophy in Mus musculus castaneus mice. Mice were fed a high‐fat diet for four weeks and then given streptozotocin (STZ, 40 mg kg−1 d−1 for 5 days, intraperitoneally) and fasting blood glucose (FBG) levels were tested after seven days. Mice with FBG levels above 11.1 mmol/L were considered diabetic. Diabetic mice continued to have access to the high‐fat diet until cardiac hypertrophy developed. FBG and body weight (BW) were measured weekly. Myocardial hypertrophy was confirmed by left ventricle (LV) hypertrophy index (LVHI), LV/BW, LV histopathological observation and atrial natriuretic factor (ANF) mRNA expression. Serum insulin and plasma haemoglobin A1c (HbA1c) levels, total cholesterol (TCH) and triglyceride (TG) were measured, and then an insulin resistance index (HOMA.IR) was calculated. The level of FBG in the model group remained above 11.1 mmol/L, and the BW showed significant weight loss, compared with the control group (P < 0.01). The high levels of HbA1c, HOME.IR, TCH and TG, and the low level of insulin suggested that glucose metabolism was not balanced with insulin resistance; meanwhile, higher TCH and TG showed that dyslipidaemia had also developed. After the diabetic mice were kept on the high‐energy diet for another four weeks, histopathological observation showed myocardial injuries, much more surface area and collagen fibres, higher LVHI and LV/BW, and elevated expression of ANF mRNA (P < 0.01), suggesting that myocardial hypertrophy had appeared in Mus musculus castaneus mice under the current experimental conditions. Thus a robust model of diabetic myocardial hypertrophy was established four weeks after confirmation of diabetes, which was induced by feeding a high‐fat diet for four weeks combined with a repeated low‐dose STZ exposure, in Mus musculus castaneus mice.

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“…The mechanism underlying this process are multifactorial and poorly understood. As a result, no treatment is available to prevent or reverse this pathological change (Kawamura et al, 2017;Lorenzo-Almorós et al, 2017;Tate et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

Mai

et al. 2020

Front. Cell Dev. Biol.

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As an important complication of diabetes mellitus, diabetic cardiomyopathy (DCM) is characterized by a silent development in its earlier stage and a deficient cardiomyocyte contractility in its late stage. So far, little advance has been achieved to reverse this pathological change. LncRNAs are defined as a large cluster of RNAs without the function of encoding proteins, but have the capacity in controlling gene expression. Interleukin-17 (IL-17), a proinflammatory cytokine, is a key regulator of host inflammation. Clinically, it plays a crucial role in the pathogenesis of cardiac interstitial fibrosis. In this study, we reported that high glucose-induced lncRNA-MIAT upregulation is responsible for proinflammatory IL-17 production in cardiomyocytes. The underlying mechanism is likely due to that lncRNA-MIAT specific attenuates miR-214-3p-mediated inhibitory effect on IL-17 expression. As a result, attenuated IL-17 expression significantly ameliorate cardiac fibrosis, followed by improvement of cardiac contractility. Taken together, our study first suggests that lncRNA-MIAT plays a key role in DCM and targeting lncRNA-MIAT may become a potential strategy to treat DCM.

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Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy

Cited by 27 publications

References 50 publications

Fabrication and Paracrine Effect Research of Bone Marrow-Derived Endothelial Progenitor Cell Sheet

Fabrication and Paracrine Effect Research of Bone Marrow-Derived Endothelial Progenitor Cell Sheet

Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

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