Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in vivo cardiac repair

Zhu, Kai; Wu, Meiying; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Chen, Yu; Wang, Chunsheng; Shi, Jianlin

doi:10.1016/j.biomaterials.2015.10.010

Cited by 48 publications

(37 citation statements)

References 41 publications

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“…We recently successfully constructed phenylene-bridged HMONs, which were featured with a simultaneous ultralarge pore size of over 20 nm, uniform morphology, a large hollow cavity, and high dispersity ( Figure 25 a). [ 282 ] The hepatocyte growth factor (HGF)…”

Section: Mons For Regenerative Medicinementioning

confidence: 99%

Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic–Inorganic Hybridization into Frameworks

2016

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Organic-inorganic hybrid materials aiming to combine the individual advantages of organic and inorganic components while overcoming their intrinsic drawbacks have shown great potential for future applications in broad fields. In particular, the integration of functional organic fragments into the framework of mesoporous silica to fabricate mesoporous organosilica materials has attracted great attention in the scientific community for decades. The development of such mesoporous organosilica materials has shifted from bulk materials to nanosized mesoporous organosilica nanoparticles (designated as MONs, in comparison with traditional mesoporous silica nanoparticles (MSNs)) and corresponding applications in nanoscience and nanotechnology. In this comprehensive review, the state-of-art progress of this important hybrid nanomaterial family is summarized, focusing on the structure/composition-performance relationship of MONs of well-defined morphology, nanostructure, and nanoparticulate dimension. The synthetic strategies and the corresponding mechanisms for the design and construction of MONs with varied morphologies, compositions, nanostructures, and functionalities are overviewed initially. Then, the following part specifically concentrates on their broad spectrum of applications in nanotechnology, mainly in nanomedicine, nanocatalysis, and nanofabrication. Finally, some critical issues, presenting challenges and the future development of MONs regarding the rational synthesis and applications in nanotechnology are summarized and discussed. It is highly expected that such a unique molecularly organic-inorganic nanohybrid family will find practical applications in nanotechnology, and promote the advances of this discipline regarding hybrid chemistry and materials.

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Section: Mons For Regenerative Medicinementioning

confidence: 99%

Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic–Inorganic Hybridization into Frameworks

2016

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“…For an angiogenesis application, stem cells as well as somatic cells have both been genetically modified. Mesenchymal stem cells (MSCs) transfected with dextran – pAdrenomedullin complex, bile acid-conjugated PEI – hypoxia-inducible pVEGF polyplex, or hollow mesoporous organosilica – pHGF nanoparticles demonstrated increased neovascularization, reduced infarct size, and improved cardiac function in rats following transplantation to myocardial infarct tissue [131–133]. Specifically, dextran-pAdrenomedulin complexed at 2.6 w/w ratio formed nanoparticles with 200 nm size and 12 mV surface charge that not only exhibited 2.5-fold increase in capillary density and 40% reduction in infarct size, but also higher recovery rate of heart function, including left ventricle end-diastolic pressure (EDP) and fraction shortening (FS).…”

Section: Pro-angiogenesismentioning

confidence: 99%

Gene delivery nanoparticles to modulate angiogenesis

Kim

Mirando

Popel

et al. 2017

Advanced Drug Delivery Reviews

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Angiogenesis is naturally balanced by many pro- and anti-angiogenic factors while an imbalance of these factors leads to aberrant angiogenesis, which is closely associated with many diseases. Gene therapy has become a promising strategy for the treatment of such a disordered state through the introduction of exogenous nucleic acids that express or silence the target agents, thereby engineering neovascularization in both directions. Numerous non-viral gene delivery nanoparticles have been investigated towards this goal, but their clinical translation has been hampered by issues associated with safety, delivery efficiency, and therapeutic effect. This review summarizes key factors targeted for therapeutic angiogenesis and anti-angiogenesis gene therapy, non-viral nanoparticle-mediated approaches to gene delivery, and recent gene therapy applications in pre-clinical and clinical trials for ischemia, tissue regeneration, cancer, and wet age-related macular degeneration. Enhanced nanoparticle design strategies are also proposed to further improve the efficacy of gene delivery nanoparticles to modulate angiogenesis.

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“…The majority of the investigations sought to enhance the expression of a certain gene [23,24,61,63,66,74,76,102,104,109,110,117] or to transfect cells with microRNAs (miRs) [16,19]. The only example of gene repression was reported by Wang et al [39], who described the silencing of prolyl hydroxylase domain protein 2 gene (PHD2) as an alternative combined genetic and cell therapy approach.…”

Section: Genetic Engineeringmentioning

confidence: 99%

“…This matter can be easily overcome by developing safer transfection methods such as electroporation [76] or through the use of non-viral plasmids [63,109] or lipid-based transfection reagents [16]. Recently, Zhu et al [24] developed an alternative transfection vehicle based on organicinorganic hybrid mesoporous organosilica nanoparticles, which offers several advantages over the common transfection vectors, namely higher biocompatibility and loading capacity, as well as easier internalization and lesser cytotoxicity. In this study, BMMNC were transfected with a HGF gene and the transformed cells were injected in rats subjected to AMI.…”

Section: Genetic Engineeringmentioning

confidence: 99%

“…connexin-43 overexpression [63]); stimulating angiogenesis (SVVYGLR peptide overexpression [66]) or simply by enhancing the positive paracrine growth factor-related stimulation (e.g. HGF [24], IGF-1 [61,117] or recombinant glucagon-like peptide-1 (GLP-1) overexpression [102,104]). Regardless of the strategy, it was constantly observed a better outcome in genetically modified stem cells in comparison to naïve cells in, at least, one criterion.…”

Section: Genetic Engineeringmentioning

confidence: 99%

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Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Trindade

Leite‐Moreira

Ferreira-Martins

et al. 2017

International Journal of Cardiology

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Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3 years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting.

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Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in vivo cardiac repair

Cited by 48 publications

References 41 publications

Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic–Inorganic Hybridization into Frameworks

Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic–Inorganic Hybridization into Frameworks

Gene delivery nanoparticles to modulate angiogenesis

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

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