Non-viral oligonucleotide antimiR-138 delivery to mesenchymal stem cell sheets and the effect on osteogenesis

Yan, Jun; Zhang, Chengcheng; Zhao, Yantao; Cao, Can; Wu, Kaimin; Zhao, Lei; Zhang, Yumei

doi:10.1016/j.biomaterials.2014.05.089

Cited by 84 publications

(74 citation statements)

References 29 publications

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“…23 Thus, it would be highly significant to explore further the performance by DNA or RNA delivery. 8 In this work, we aimed to verify the feasibility of miR-21 delivery to cell sheets, with a safer nonviral approach than the viral approach, for enhanced osteogenic potential. In this study, we …”

Section: Discussionmentioning

confidence: 99%

“…6,7 The cell sheets could be applied layer by layer and could attach well to defective areas of tissues, allowing for either direct in vivo transplantation or combination with biomaterials in tissue engineering. 8 This technique has proved effective in treating esophageal ulcerations, 9 periodontal tissue destruction, 3 corneal dysfunction, 10 myocardial infarction, 2 and so on. Thus, we expect that producing higher-quality cell sheets with in vitro-induced specific lineage differentiation capacities would result in superior biological performance for specific tissue regeneration.…”

mentioning

confidence: 99%

“…13 Although specific miRNAs have been widely delivered into isolated stem cells, they have only rarely been delivered into cell sheets, especially with an efficient reverse transfection approach. 8 It would be of great significance to explore efficient and practical miRNA delivery approaches during cell sheet formation for enhanced clinical performance.…”

mentioning

confidence: 99%

“…6,8,23 Vc was demonstrated to be capable of stimulating the ECM deposition of stem cells, thereby promoting cell sheet formation. 6 In this work, the Vc-based method was chosen to generate the hBMMSC sheets.…”

mentioning

confidence: 99%

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Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Wang

Wu²,

Wei

et al. 2016

IJN

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Cell sheet engineering has emerged as a novel approach to effectively deliver seeding cells for tissue regeneration, and developing human bone marrow mesenchymal stem cell (hBMMSC) sheets with high osteogenic ability is a constant requirement from clinics for faster and higher-quality bone formation. In this work, we fabricated biocompatible and safe chitosan (CS)/hyaluronic acid (HA) nanoparticles (NPs) to deliver microRNA-21 (miR-21), which has been proved to accelerate osteogenesis in hBMMSCs; then, the CS/HA/miR-21 NPs were cross-linked onto the surfaces of culture plates with 0.2% gel solution to fabricate miR-21-functionalized culture plates for reverse transfection. hBMMSC sheets were induced continuously for 14 days using a vitamin C-rich method on the miR-21-functionalized culture plates. For the characterization of CS/HA/miR-21 NPs, the particle size, zeta potential, surface morphology, and gel retardation were sequentially investigated. Then, the biological effects of hBMMSC sheets on the miR-21-functionalized culture plates were evaluated. The assay results demonstrated that the hBMMSC sheets could be successfully induced via the novel reverse transfection approach, and miR-21 delivery significantly enhanced the in vitro osteogenic differentiation of hBMMSC sheets in terms of upregulating calcification-related gene expression and enhancing alkaline phosphatase production, collagen secretion, and mineralized nodule formation. The enhanced osteogenic activity of hBMMSC sheets might promisingly lead to more rapid and more robust bone regeneration for clinical use.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Wang

Wu²,

Wei

et al. 2016

IJN

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“…The abovementioned non-viral vectors are viable in delivering therapeutic genes, such as osterix [42], core-binding factor alpha 1 [43], and BMP2 [44], for bone regeneration [45]. Recently, cell sheets were engineered using LipofectamineR 2000 to produce anti-miR-138, a microRNA precursor family [46]. These cell sheets with high cell number and good cell-cell contact uses the scaffold-free tissue engineering approach and can be easily layered and attached to tissue beds.…”

Section: Techniques For Engineering Mscmentioning

confidence: 99%

Engineering mesenchymal stem cells for regenerative medicine and drug delivery

Park

Suryaprakash

Lao

et al. 2015

Methods

194

156

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Researchers have applied mesenchymal stem cells (MSC) to a variety of therapeutic scenarios by harnessing their multipotent, regenerative, and immunosuppressive properties with tropisms toward inflamed, hypoxic, and cancerous sites. Although MSC-based therapies have been shown to be safe and effective to a certain degree, the efficacy remains low in most cases when MSC are applied alone. To enhance their therapeutic efficacy, researchers have equipped MSC with targeted delivery functions using genetic engineering, therapeutic agent incorporation, and cell surface modification. MSC can be genetically modified virally or non-virally to overexpress therapeutic proteins that complement their innate properties. MSC can also be primed with non-peptidic drugs or magnetic nanoparticles for enhanced efficacy and externally regulated targeting, respectively. Furthermore, MSC can be functionalized with targeting moieties to augment their homing toward therapeutic sites using enzymatic modification, chemical conjugation, or non-covalent interactions. These engineering techniques are still works in progress, requiring optimization to improve the therapeutic efficacy and targeting effectiveness while minimizing any loss of MSC function. In this review, we will highlight the advanced techniques of engineering MSC, describe their promise and the challenges of translation into clinical settings, and suggest future perspectives on realizing their full potential for MSC-based therapy.

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A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles

Sadowska,

Power,

Genoud

et al. 2023

Advanced Materials

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Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long‐term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi‐faceted solution would will eradicate bacterial infection without long‐term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen‐based scaffold that addresses these needs by leveraging the potential of antibiotic‐free antimicrobial nanoparticles (copper‐doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA‐based gene therapy (utilizing an inhibitor of microRNA‐138) to stimulate both osteogenesis and angiogenesis, is developed. CuBG scaffolds reduce the attachment of gram‐positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR‐138 nanoparticles induce osteogenesis of human mesenchymal stem cells in vitro and heal a large load‐bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies results in a multifunctional antagomiR‐138‐activated CuBG scaffold inducing hMSC‐mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyzes killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi‐functional strategy for treating and repairing complex bone infections.

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Non-viral oligonucleotide antimiR-138 delivery to mesenchymal stem cell sheets and the effect on osteogenesis

Cited by 84 publications

References 29 publications

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Engineering mesenchymal stem cells for regenerative medicine and drug delivery

A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles

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