A naturally derived dextran-peptide vector for microRNA antagomir delivery
cells; Chemistry; gene delivery; human cancers; in-vitro; mechanism; RNA interference; therapy; vivo
Single stranded microRNAs and their antagomirs are unstable and polyanionic, which impedes efficient cellular uptake and reduces half-life. Therefore, effective delivery systems with low toxicity for microRNAs are urgently needed for the success of microRNA-based therapy. Here, a dextran-peptide hybrid, Dex10-R5H5(40%), was developed as a carrier to deliver microRNAs. Dex10-R5H5(40%) loaded with antagomir-149 could reduce the level of endogenous microRNA-149 by 76% and it is more effective than the commercially available transfection reagent, RNAiMAX, which leads to 67% reduction. Additionally, Dex10-R5H5(40%) exhibited no cytotoxicity to HepG2 cells. These results indicate that the dextran-peptide hybrid may be a promising delivery system for the safe and efficient microRNA-based therapy.
Tang Q; Lei X; Cao B; Sun B B; Zhang Y Q; Cheng G
Rsc Advances
2015
2015
Journal Article
<a href="http://doi.org/10.1039/c4ra12878h" target="_blank" rel="noreferrer noopener">10.1039/c4ra12878h</a>
Comparison Of Different Chondrocytes For Use In Tissue Engineering Of Cartilage Model Structures
articular-cartilage; auricular cartilage; Cell Biology; construct; growth; in-vitro; regeneration; scaffold; shape; stem-cells; vivo
This study compares bovine chondrocytes harvested from four different animal locations-nasoseptal, articular, costal, and auricular-for tissue-engineered cartilage modeling. While the work serves as a preliminary investigation for fabricating a human ear model, the results are important to tissue-engineered cartilage in general. Chondrocytes were cultured and examined to determine relative cell proliferation rates, type II collagen and aggrecan gene expression, and extracellular matrix production. Respective chondrocytes were then seeded onto biodegradable poly(L-lactide-epsilon-caprolactone) disc-shaped scaffolds. Cell-copolymer constructs were cultured and subsequently implanted in the subcutaneous space of athymic mice for up to 20 weeks. Neocartilage development in harvested constructs was assessed by molecular and histological means. Cell culture followed over periods of up to 4 weeks showed chondrocyte proliferation from the tissue sources varied, as did levels of type II collagen and aggrecan gene expression. For both genes, highest expression was found for costal chondrocytes, followed by nasoseptal, articular, and auricular cells. Retrieval of 20-week discs from mice revealed changes in construct dimensions with different chondrocytes. Greatest disc diameter was found for scaffolds seeded with auricular chondrocytes, followed by those with costal, nasoseptal, and articular cells. Greatest disc thickness was measured for scaffolds containing costal chondrocytes, followed by those with nasoseptal, auricular, and articular cells. Retrieved copolymer alone was smallest in diameter and thickness. Only auricular scaffolds developed elastic fibers after 20 weeks of implantation. Type II collagen and aggrecan were detected with differing expression levels on quantitative RT-PCR of discs implanted for 20 weeks. These data demonstrate that bovine chondrocytes obtained from different cartilaginous sites in an animal may elicit distinct responses during their respective development of a tissue-engineered neocartilage. Thus, each chondrocyte type establishes or maintains its particular developmental characteristics, and this observation is critical in the design and elaboration of any tissue-engineered cartilage model.
Isogai N; Kusuhara H; Ikada Y; Ohtani H; Jacquet R; Hillyer J; Lowder E; Landis W J
Tissue Engineering
2006
2006-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1089/ten.2006.12.691" target="_blank" rel="noreferrer noopener">10.1089/ten.2006.12.691</a>