Nonviral delivery of siRNA into mesenchymal stem cells by a combination of ultrasound and microbubbles

Preparation and Characterization of Genetically Engineered Mesenchymal Stem Cell Aggregates for Regenerative Medicine

“…Induction of in vitro gene expression is highly dependent upon the selection of appropriate gene carriers, and dependent on cell-related factors such as cell type and cell conditions. Since primary cells including adult bone marrow-derived MSCs show very low in vitro transfection efficiencies of generally no more than a few percent using common transfection methodologies (HaleemSmith et al, 2005;Otani et al, 2009), the development of efficient transfection reagents for MSCs is needed for successful therapeutic approaches using genetically engineered MSC aggregates. To exclude the possibility that the genetic modification and cell aggregation processes caused phenotypic changes of the MSCs, phenotypic analysis of intact MSCs and eGFP-modified MSC aggregates was conducted by flow cytometry after staining for positive (CD90) and negative (CD34) MSC membrane surface markers.…”

Feasibility of Clinical Application of Ultrasound Molecular Imaging

“…Therefore, the development of clinically translatable targeted bubbles has potential for spreading ultrasound molecular imaging into clinical settings rapidly. In parallel with perfusion or molecular imaging, the potential of microbubbles as a carrier for drug or gene delivery into cells has been demonstrated recently in both in vitro and in vivo studies (Liu et al, 2006;Otani et al, 2009;Tinkov et al, 2009). The combination of these features might lead to the localized delivery of drugs or genes into target cells in vivo.…”

Potential and problems in ultrasound-responsive drug delivery systems

“…[4][5][6][7] In recent times, drug-loaded ultrasound contrast agent systems, also termed ultrasound-responsive drug delivery systems (URDDS), have become an increasing focus of research. URDDS include microbubbles, [8][9][10] nanobubbles, 11,12 nanodroplets, 13 liposomes, 14,15 emulsion, 16 and micelles. [17][18][19] A combination of two or more formulations can be used as URDDS, such as liposomal bubbles 20,21 and microemulsions.…”

“…[17][18][19] A combination of two or more formulations can be used as URDDS, such as liposomal bubbles 20,21 and microemulsions. 22 The drugs loaded can include inorganic substances, eg, titanium dioxide, 23 small molecules (curcumin, 24 doxorubicin, 25 cisplatin, 5 epirubicin hydrochloride, 26 10-hydroxycamptothecin 27 ), proteins, 28,29 small interfering RNA, 8,21 DNA, 30 and antisense oligodeoxynucleotides. 31,32 Their therapeutic applications include anticancer therapy, 23,33 treatment of ischemic myocardium, 29 induction of an immune response, 34 cartilage tissue engineering, 35 transdermal drug delivery, 36,37 treatment of Huntington's disease 38 and thrombolysis, 39,40 and disruption of the blood-brain barrier.…”