Directing stem cell fate by controlled RNA interference

Yau, Winifred Wing Yiu; Rujitanaroj, Pim-on; Lam, Ling Ning; Chew, Sing Yian

doi:10.1016/j.biomaterials.2011.12.021

Cited by 80 publications

(81 citation statements)

References 93 publications

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“…The use of growth/differentiation factors to induce stem cell differentiation in vivo has some limitations such as short half-lives, denaturation during the encapsulation processes, time-consuming, long time periods to obtain the differentiated cells, use of cocktails of GFs and difficulty to differentiate the cells into one specific lineage [108,162]. Therefore, gene therapy, encoding transcription factors or encoding for a specific or to a set of proteins may be a good approach to overcome these limitations and to control stem cell differentiation [124].…”

Section: Therapeutic Gene Deliverymentioning

confidence: 99%

“…Therefore, therapeutic proteins or GFs are produced using the cell machinery outside of the nucleus. Another way to control stem cell differentiation relies on the delivery of RNAi, as previously mentioned [162]. RNAi acts by binding to nucleic acids, inhibiting gene transcription and translation; in other words, RNAi acts by silencing genes of interest through the eradication of target mRNAs through the introduction of small interfering RNAs (siRNAs), small hairpin RNAs (shRNAs) or micro-RNAs (miRNAs) [25,108,162].…”

Section: Therapeutic Gene Deliverymentioning

confidence: 99%

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Liposomes in tissue engineering and regenerative medicine

Monteiro

Martins

Reis

et al. 2014

J. R. Soc. Interface.

317

217

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Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches.

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Section: Therapeutic Gene Deliverymentioning

confidence: 99%

Section: Therapeutic Gene Deliverymentioning

confidence: 99%

Liposomes in tissue engineering and regenerative medicine

Monteiro

Martins

Reis

et al. 2014

J. R. Soc. Interface.

317

217

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“…Sox1 is a particularly strong indicator of neural induction, as it is one of the earliest transcription factors expressed in ectodermal cells committed to a neural lineage and upregulation of Sox1 is directly correlated to neural determination and differentiation. 23,24 As shown in Figure 6C, fibroblast reprogramming using nanoparticles to deliver Sox2 led to an eight-fold increase in Sox1 expression over untreated cells and a 6-fold increase over Lipofectamine by day 12. This indicated increased levels of neural differentiation in the cells treated with Sox2 pDNA via this silica-stabilized and multistage polyplex delivery system.…”

mentioning

confidence: 90%

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres

Pandit

Watson

Ren

et al. 2015

Tissue Engineering Part C: Methods

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Polycationic nanocomplexes are a robust means for achieving nucleic acid condensation and efficient intracellular gene deliveries. To enhance delivery, a multilayered nanoparticle consisting of a core of electrostatically bound elements was used. These included a histone-mimetic peptides, poly-l-arginine and poly-d-glutamic acid was coated with silicate before surface functionalization with poly-l-arginine. Transfection efficiencies and duration of expression were similar when using green fluorescent protein (GFP) plasmid DNA (pDNA) or GFP mRNA. These nanoparticles demonstrated significantly higher ( > 100%) and significantly longer (15 vs. 4 days) transfection efficiencies in comparison to a commercial transfection agent (Lipofectamine 2000). Reprogramming of human foreskin fibroblasts using mRNA to the Sox2 transcription factor resulted in three-fold higher neurosphere formation in comparison to the commercial reagent. These results demonstrate the potential of these nanoparticles as ideal vectors for gene delivery.

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“…Consequently, miRNAs have become important tools in biological and medical research and are increasingly applied to treat and monitor disease. Overexpression or inhibition of miRNAs can simultaneously modulate the endogenous expression of multiple growth factors (Yau et al, 2012). Therefore, delivery of select miRNAs might optimise bone regeneration by coordinating endogenous angiogenesis and osteogenesis .…”

Section: Introductionmentioning

confidence: 99%

Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds

Deng

Bi²,

Zhou³

et al. 2014

eCM

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The repair of critical-sized defects (CSDs) is a significant challenge in bone tissue engineering. Combining the use of progenitor cells with gene therapy represents a promising approach for bone regeneration. MicroRNAs play important roles in most gene regulatory networks, regulate the endogenous expression of multiple growth factors and simultaneously modulate stem cell differentiation. Our previous study showed that knocking down miR-31 promotes the osteogenesis of bone marrow stromal stem cells (BMSCs). To investigate the therapeutic potential of cells engineered to express anti-miR-31 for CSD repair, lentiviral vectors encoding negative control, miR-31 precursor and anti-sense sequences were constructed and transduced into osteo-inductive BMSCs. The expression of osteogenic-specific genes, alkaline phosphatase activity and Alizarin Red S staining were investigated to evaluate the effects of miR-31 on the cell fate of BMSCs over a 3-week period. In addition, miR-31-modified BMSCs seeded on poly(glycerol sebacate) (PGS) scaffolds were used to repair 8 mm critical-sized calvarial defects in rats. The results showed that miR-31 suppression significantly increased the expression of osteogenic-specific genes in vitro at the mRNA and protein levels, and that robust new bone formation with high local bone mineral density was observed in the anti-miR groups in vivo. Moreover, the PGS scaffolds carrying anti-miR-31-expressing BMSCs exhibited good biocompatibility and a high regeneration rate (~60 %) within in vivo bone defects. Our results suggest that miR-31 gene delivery affects the potential of BMSCs for osteogenic differentiation and bone regeneration and that PGS is a potential substrate for genetically modified, tissue-engineered bone in the repair of large bone defects.

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Directing stem cell fate by controlled RNA interference

Cited by 80 publications

References 93 publications

Liposomes in tissue engineering and regenerative medicine

Liposomes in tissue engineering and regenerative medicine

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres

Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds

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