Silica Nanoparticles Actively Engage With Mesenchymal Stem Cells in Improving Acute Functional Cardiac Integration

Popara, Jasmin; Accomasso, Lisa; Vitale, Emanuela; Gallina, Clara; Roggio, Dorotea; Iannuzzi, Ambra; Raimondo, Stefania; Rastaldo, Raffaella; Alberto, Gabriele; Catalano, Federico; Martra, Gianmario; Turinetto, Valentina; Pagliaro, Pasquale; Giachino, Claudia

doi:10.2217/nnm-2017-0309

Cited by 25 publications

(24 citation statements)

References 57 publications

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“…MSCs can differentiate into cardiomyocytelike cells, integrate into host tissue, and enhance resident cell activity [138]. With the help of nano-biomaterials, MSCs have achieved better differentiation and functional integration for repairing myocardial infarction repair [139][140][141]. Transplanted MSCs can integrate into partially hepatectomized or toxicinjured liver for hepatic regeneration [142,143].…”

Section: Integration Of Differentiated Mscsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

390

282

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Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

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Section: Integration Of Differentiated Mscsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

390

282

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“…Limited studies provided the vascular injury and dysfunction caused after SiNPs inhalation, probably associated with oxidative stress and inflammatory response [27]. In contrast, studies pointed out the good biological safety of SiNPs, which could improve the efficacy of cell therapy for myocardial infarction, and was considered the best candidate for stem cell therapy in cardiac tissue [28]. Owing to controversial results and to the lack of sufficient data to clearly identify the pro-atherogenic effects of SiNPs, we aim to study the long-term influence of SiNPs on the progression of atherosclerotic plaque by using ApoE-knockout (ApoE −/− ) mice fed a Western diet and conduct in vitro experiments for mechanism research.…”

Section: Introductionmentioning

confidence: 99%

Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE−/− mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage

Zhao

et al. 2020

Part Fibre Toxicol

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Background The biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been gradually confirmed, however, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms. Results We firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE−/− mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group, and the histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE−/− mice. Compared to the control group, the serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression induced by SiNPs. Conclusions Our results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE−/− mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage. Graphical abstract

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“…NPs may be a potential approach to address this problem. It has been demonstrated that NPs can enhance stem cell retention by providing a cardiac-specific extracellular matrix (ECM) environment (include impacts some signal pathway), affecting the focal adhesion complex of myocardial MSCs (Bejleri et al, 2018), promoting the interactions with cardiomyocytes and affecting lysosomal function in ischemic environments (Popara et al, 2018). Magnetic NPs seem to resolve this accumulation to some extent.…”

Section: Nps Enhance Stem Cell Retention After Transplantationmentioning

confidence: 99%

The Roles of Nanoparticles in Stem Cell-Based Therapy for Cardiovascular Disease

Sun

et al. 2020

Front. Bioeng. Biotechnol.

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Cardiovascular disease (CVD) is currently one of the primary causes of mortality and morbidity worldwide. Nanoparticles (NPs) are playing increasingly important roles in regulating stem cell behavior because of their special features, including shape, size, aspect ratio, surface charge, and surface area. In terms of cardiac disease, NPs can facilitate gene delivery in stem cells, track the stem cells in vivo for long-term monitoring, and enhance retention after their transplantation. The advantages of applying NPs in peripheral vascular disease treatments include facilitating stem cell therapy, mimicking the extracellular matrix environment, and utilizing a safe non-viral gene delivery tool. However, the main limitation of NPs is toxicity, which is related to their size, shape, aspect ratio, and surface charge. Currently, there have been many animal models proving NPs' potential in treating CVD, but no extensive applications of stem-cell therapy using NPs are available in clinical practice. In conclusion, NPs might have significant potential uses in clinical trials of CVD in the future, thereby meeting the changing needs of individual patients worldwide.

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Silica Nanoparticles Actively Engage With Mesenchymal Stem Cells in Improving Acute Functional Cardiac Integration

Abstract: These findings provide strong evidence that SiO-NPs actively engage in mediating biological effects, ultimately resulting in augmented hMSC acute cardiac integration potential.

Cited by 25 publications

References 57 publications

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE−/− mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage

The Roles of Nanoparticles in Stem Cell-Based Therapy for Cardiovascular Disease

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